Professional Documents
Culture Documents
Algorithms in
Pediatric
Nephrology
Editors
Israel Zelikovic, Haifa
Israel Eisenstein, Haifa
26 Fetal hydronephrosis
Tubular disease
J.-P. Guignard; R.N. Fine
Glomerular and vascular disease
54 Aminoaciduria
28 Vesicourethral reflux
4 Hematuria I. Eisenstein; P. Goodyer; I. Zelikovic
R. Adelman; S. Hulton
A.L. Friedman; S. Turi
30 Dysfunctional voiding 56 Cystinuria
6 Acute nephritic syndrome P. Goodyer; I. Eisenstein; I. Zelikovic
S. Hulton; R. Adelman
F. Santos; S.P. Makker
32 Loin pain with hematuria 58 Glycosuria
8 Proteinuria I. Eisenstein; P. Goodyer; I. Zelikovic
J. Smith; F.B. Stapleton
F. Santos; S.P. Makker
34 Renal trauma 60 Renal tubular acidosis
10 Nephrotic syndrome in the first year I. Eisenstein; P. Goodyer; I. Zelikovic
R. Adelman; S. Hulton
of life
36 Tubulointerstitial nephritis 62 Proximal tubulopathy
F. Santos; S.P. Makker
A.L. Friedman; S. Turi (Fanconi syndrome)
12 Nephrotic syndrome in the child and P. Goodyer; I. Eisenstein; I. Zelikovic
adolescent 64 Polyuria
S.P. Makker; F. Santos Structural/congenital abnormalities P. Goodyer; I. Eisenstein; I. Zelikovic
14 Rapidly progressive 38 Single kidney (renal agenesis) 66 Hypouricemia
glomerulonephritis G. Rizzoni ; M.A. Linshaw J. Smith; F.B. Stapleton
S.P. Makker; F. Santos
40 Renal hypoplasia-dysplasia 68 Hyperuricemia
16 Chronic nephritic syndrome G. Rizzoni ; M.A. Linshaw F.B. Stapleton; J. Smith
S.P. Makker; F. Santos
42 Nephromegaly 70 Rickets
18 Vasculitis M.A. Linshaw; G. Rizzoni G. Ariceta; B. Hoppe; C.B. Langman
W. Proesmans; U.S. Alon
44 Hyperechoic kidney
20 Hemolytic uremic syndrome M.A. Linshaw; G. Rizzoni
W. Proesmans; U.S. Alon
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M.A. Linshaw; G. Rizzoni
Fluid/electrolyte/acid base balance Divalent ion metabolism Renal failure
72 Hyponatremia 92 Hypocalcemia 106 Oliguria/anuria
S. Watkins; D. Okamura; J. Rodrguez Soriano G. Ariceta; B. Hoppe; C.B. Langman J.-P. Guignard; R.N. Fine
86 Metabolic alkalosis
U.S. Alon; W. Proesmans
88 Hypovolemia
U.S. Alon; W. Proesmans
90 Edema
W. Proesmans; U.S. Alon
III
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Practical algorithms in pediatric nephrology / editors, Israel Zelikovic, not of the publisher and the editor(s). The appearance of advertise- electronic or mechanical, including photocopying, recording, micro-
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p. ; cm. -- (Practical algorithms in pediatrics) products or services advertised or of their effectiveness, quality or permission in writing from the publisher.
Includes bibliographical references and index. safety. The publisher and the editor(s) disclaim responsibility for any
ISBN 978-3-8055-8539-2 (soft cover : alk. paper) injury to persons or property resulting from any ideas, methods, in- Copyright 2008 by S. Karger AG, P.O. Box, CH4009 Basel
1. Pediatric nephrology--Handbooks, manuals, etc. 2. Medical structions or products referred to in the content or advertisements. (Switzerland)
protocols--Handbooks, manuals, etc. I. Zelikovic, Israel. II. Eisenstein, Printed in Switzerland on acid-free and non-aging paper (ISO 9706)
Israel, 1964- III. Series. Drug Dosage. The authors and the publisher have exerted every effort by Reinhardt Druck, Basel
[DNLM: 1. Kidney Diseases--diagnosis. 2. Adolescent. 3. Child. 4. to ensure that drug selection and dosage set forth in this text are in ISBN 9783805585392
Decision Trees. 5. Diagnosis, Differential. WS 320 P895 2008] accord with current recommendations and practice at the time of pub-
RJ476.K5P73 2008 lication. However, in view of ongoing research, changes in government
618.9261--dc22 regulations, and the constant flow of information relating to drug ther-
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Contributors
Raymond Adelman, MD Bernd Hoppe, MD Juan Rodrguez Soriano, MD
Department of Pediatrics University Childrens Hospital Division of Pediatric Nephrology
Phoenix Childrens Hospital Division of Pediatric Nephrology Department of Pediatrics
Phoenix, AZ, USA Cologne, Germany Hospital de Cruces and Basque University
School of Medicine
Uri S. Alon, MD Sally Hulton, MD Baracaldo, Vizcaya, Spain
Section of Pediatric Nephrology Department of Pediatric Nephrology
The Childrens Mercy Hospital and Clinics The Birmingham Childrens Hospital Fernando Santos, MD
University of Missouri NHS Trust Division of Pediatric Nephrology
Kansas City, MO, USA Birmingham, United Kingdom Hospital Central de Asturias
University of Oviedo
Gema Ariceta, MD Craig B. Langman, MD Oviedo, Asturias, Spain
Division of Pediatric Nephrology Feinberg School of Medicine
Hospital de Cruces Northwestern University Jodi Smith, MD
Baracaldo, Vizcaya, Spain Kidney Diseases, Childrens Memorial Hospital Division of Pediatric Nephrology
Chicago, IL, USA Childrens Hospital and Regional Medical Center
Israel Eisenstein, MD University of Washington
Michael A. Linshaw, MD Seattle, WA, USA
Pediatric Nephrology
Rambam Medical Center Division of Pediatric Nephrology
Faculty of Medicine Technion Massachusetts General Hospital F. Bruder Stapleton, MD
Haifa, Israel Boston, MA, USA Department of Pediatrics
Childrens Hospital and Regional Medical Center
Richard N. Fine, MD Sudesh Paul Makker, MD University of Washington
Seattle, WA, USA
School of Medicine Pediatric Nephrology
State University of New York at Stony Brook UC Davis Medical Center
Stony Brook, NY, USA Sacramento, CA, USA Sandor Turi, MD
Department of Pediatrics and Child Health Center
Aaron L. Friedman, MD Daryl Okamura, MD University of Szeged
Szeged, Hungary
Department of Pediatrics Division of Pediatric Nephrology
University of Minnesota Childrens Hospital and Regional Medical Center
Minneapolis, MN, USA University of Washington Sandra Watkins, MD
Seattle, WA, USA Division of Pediatric Nephrology
Paul Goodyer, MD Childrens Hospital and Regional Medical Center
Willem Proesmans, MD University of Washington
Division of Pediatric Nephrology
Seattle, WA, USA
The Montreal Childrens Hospital Renal Unit, Department of Pediatrics
McGill University University Hospital Gasthuisberg
Montreal, Quebec, Canada Leuven, Belgium Israel Zelikovic, MD
1 Pediatric Nephrology
Jean-Pierre Guignard, MD Gianfranco Rizzoni , MD Rambam Medical Center
Faculty of Medicine Technion
Division of Pediatric Nephrology Division of Nephrology
Haifa, Israel
Department of Pediatrics Childrens Hospital and
/
Hematuria
4
Urinary symptoms Edema, fever Urine: microscopy, culture, protein, Recurrent/new onset ? Blood pressure, Urine: microscopy, protein,
Stones/urinary sediment Abdominal/loin metabolic profile of stones Postinfectious respiratory rate, eosinophils
Abdominal/loin pain mass or tenderness Serum: creatinine and BUN, electrolytes, Ca2+, Rash, arthritis/arthralgia pallor, edema, Serum: CBC + reticulocytes,
Weight loss Eye/ear examination phosporus, uric acid, CBC + reticulocytes, Hemoptysis rash, petechia, creatinine, BUN, electrolytes,
Hearing impairment Diaper/underwear blood gases, LDH, C3, C4, ANA, ANCA Respiratory symptoms arthritis/arthralgia, AST, ALT, albumin,
Eye anomalies sediment Hepatitis B, C serology Weight loss, fever lung examination hepatitis B, C serology,
(+)Family Hx of stones/ Bruises/hematomas Imaging: plain abdominal film, Drugs (NSAID, antibiotics) C3, C4, ANA, ANCA
hearing impairment/hematuria/ renal/abdominal Doppler US, Kidney biopsy
bleeding disorder/ abdominal CT, angiography, kidney biopsy
hypercoagulability
Fever Glomerular disease 5 Urinary tract diseases 8 Immune-mediated disease ; Vasculitides < Miscellaneous =
Strenuous exercise Alport syndrome Urinary tract infection Postinfectious glomerulonephritis HSP RPGN
Benign familial hematuria Nephro-/urolithiasis Other glomerulonephritides Wegner's granulomatosis HUS
IgA nephropathy Hypercalciuria (shunt GN, SBE, cryoglobulinemia) Churg-Strauss syndrome TIN
Postinfectious glomerulonephritis Loin pain hematuria syndrome MPGN Microscopic polyangiitis
Persistent asymptomatic hematuria Hematologic diseases 9 IgA nephropathy (microscopic PAN)
Anatomic malformation 6 Coagulopathies Lupus nephritis Polyarteritis nodosa (classic PAN)
Hydronephrosis Renal vein thrombosis Anti-GBM glomerulopathy
Polycystic kidney disease Sickle cell disease (Goodpasture syndrome)
Tumors 7 Nutcracker syndrome
Wilms tumor AV malformation
/
Acute nephritic syndrome Macroscopic hematuria, oliguria, acute renal failure,
salt retention (hypertension and edema), proteinuria
Transient Persistent 3
/
Proteinuria
8
Transient 0 Persistent 1
Tubular Glomerular 4
Tubular disorders 2 Overload proteinuria 3 Nephritic syndrome 5 Nephrotic syndrome 5 Chronic renal disease 6
/
Nephrotic syndrome in the first year of life
10
Congenital NS 0 Infantile NS 0
MCD
MGN
SLE
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1 NS is characterized by massive proteinuria, pseudohermaphroditism and Wilms tumor. Incom-
Selected reading
estimated by urinary protein elimination equal to or plete forms of the syndrome have been reported. DMS
greater than 40 mg/m2/h and/or urinary protein/creati- causes ESRD in the first 2 years of life. The pathologi- Holmberg C, Tryggvason K, Kestila MK, Jalanko HJ:
nine ratio >23 mg/mg, resulting in hypoalbuminemia cal picture is characteristic and consists of mesangial Congenital nephrotic syndrome; in Avner ED,
of less than 3 g/dl, edema and hyperlipidemia. Al- matrix expansion, thickened glomerular basal mem- Harmon WE, Niaudet P (eds): Pediatric Nephrology,
though minimal change nephropathy is by far the lead- brane, tuft contraction and tubular dilatation. Muta- ed 5. Philadelphia, Lippincott-Williams & Wilkins,
ing cause of NS in childhood, when NS presents in the tions in the WT1 gene, which is expressed in podo- 2004, pp 503516.
first year of life, other underlying diseases must be cytes and epithelial cells of the Bowmans capsule of Kestila M, lenkkeri U, Mannikko N, Lamerdin J,
considered. postnatal kidney, have been found in nearly all Mc Cready P, Putaaala H, Ruotsalinen V, Morita T,
patients affected with Denys-Drash syndrome and in Nissinen M, Herva R, Kashtan DE, Peltonen L,
2 The term congenital NS is classically used to many cases of isolated DMS. Holmberg C, Olsen A, Tryggvason K: Positionally
describe a NS of onset within the first 3 months of life cloned gene for a novel glomerular protein neph-
(and has become synonymous with Finnish type NS). 6 Although FSGS is usually diagnosed in older rin is mutated in congenital nephrotic syndrome.
Infantile NS usually applies to NS of later onset, until children or adults, it can present in the first year of life. Mol Cell 1998;1:575582.
1 year of age. These cases are usually due to mutations in the gene Niaudet P, Gubler MC: WT1 and glomerular
encoding podocin, a protein which is essential in the diseases. Pediatr Nephrol 2006;21:16531660.
3 Finnish-type NS may be found worldwide formation and structure of the slit diaphragm. Two Tryggvason K, Patrakka J, Wartiovaara J: Hereditary
although it is more frequent in Finland where its inci- additional genes encoding the proteins alfa-actinin-4 proteinuria syndromes and mechanisms of protein-
dence is approximately 1/10,000 newborns. A typical and TRPC6 are known to cause FSGS when mutated, uria. N Engl J Med 2006;354:13871401.
clinical picture includes premature delivery, placenta usually in older children. These genetic defects do not
weighing more than 25% of the birth weight, develop- respond to treatment with glucocorticoids or other
ment of generalized edema, massive proteinuria and immunomodulatory drugs and no disease recurrence
hypoalbuminemia at birth or within the first days of after transplantation (which is common in idiopathic
life. In untreated cases, the natural course of the dis- FSGS) is expected.
ease leads to early death secondary to infection and/or
malnutrition in the presence of normal glomerular 7 NS in infants younger than 1 year may be
filtration rate. Proteinuria may be detected prenatally secondary to SLE, minimal-change nephropathy or
by increased concentrations of alfa-fetoprotein in membranous nephropathy. These cases are rare and
amniotic fluid. Microscopically, NS of Finnish type is for details on these disorders, see the appropriate
characterized by irregular pseudocystic dilatation of algorithms.
proximal tubules which is typically seen after the first
36 months of life. The disease follows an autosomal- 8 The management of an infant with persistent
recessive transmission and is caused by mutations in NS is complex and must be done in a highly special-
the gene NPHS1. The gene is localized to 19q13.1 and ized childrens hospital. It includes active nutritional
encodes a protein named nephrin which is essential in support, control of edema by repeated administration
the formation of the normal zipper-looking structure of intravenous albumin in association with furosemide,
in the slit diaphragm that joins the interdigitating pro- hormone replacement, prevention of thromboembolic
cesses of podoctytes. Abnormal nephrin results in a complications, and prompt and aggressive treatment
massive leak of proteins through the glomerular basal of infections. Administration of indomethacin, ACE
membrane. inhibitors, angiotensin II-type I receptor blockers to
reduce glomerular filtration rate, and, subsequently,
4 Neonatal infections, such as syphilis and less proteinuria may facilitate the control of the patient.
frequently toxoplasmosis, cytomegalovirus or hepati-
tis can cause nephrotic syndrome. These causes must 9 In spite of the above measures, infants with
be excluded by the associated clinical manifestations massive proteinuria often require early nephrectomy
and proper immunologic or serologic tests. In these and dialysis to place the patient in proper metabolic
11 cases, specific treatment of the primary disorder usu- and nutritional conditions for a successful renal trans-
ally leads to remission of the NS. plantation. Bilateral nephrectomy and chronic perito-
neal dialysis have been recommended in Finnish type
5 DMS is responsible for early-onset NS either NS when the infant weighs 7 kg. The effectiveness of
/
Nephrotic syndrome in the child and adolescent
12 History 01
Physical examination
Laboratory tests
Gross hematuria () 2 Gross hematuria (+) Microhematuria (+) Microhematuria (+) Microhematuria (+) Microhematuria ()
Microhematuria () BPM or N, GFRmor N BPM or N BPMor N BPM or N BPM or N
BP-N MASLO GFRm or N GFRmor N GFRmor N GFRmor N
GFR-N mC3, C4-N ANA (+) C3, C4-N ASLO-N C3, Cr-N, occasionallym
C3, C4-N ANA () C3, C4m mC3 ANA ()
ANA () Group A B-streptococcus in C4mor N ASLO-N
throat or skin () () ANA
Permanent Frequent relapses Steroid dependent HepB Abs (+) HepC Ab(+) ANCA (+) HIV (+) ;
remission 4
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1 NS is a clinical condition that consists of edema, heavy pro- becomes negative for protein have been used but the superiority of 9 All other glomerulonephrides producing NS are generally
teinuria, hypoalbuminemia and hyperlipidemia with or without the any one schedule is not established though recent data suggest that first treated with prednisone which is usually started at 2 mg/kg/day
accompanying hypertension and/or renal failure. Nephrotic range longer treatment (6 months) may reduce the frequency of subse- (maximum 60 mg) dose. Usually after 46 weeks, the dose is
(heavy) proteinuria is defined as protein excretion of 640 mg/h/m2 quent relapses. In general, the same dose is continued for 24 weeks switched to every other morning dose to reduce the side effects of
obtained on a timed urine collection. It is usually evident on a routine and then tapered to zero over several weeks. prednisone. The durations of daily and alternate day prednisone
urinalysis with dipstick test as 3 to 64 (300 to 61,000) mg/dl protein. administration are quite variable and not established. Various immu-
A random spot urine tested for protein and creatinine often will show 6 About 15% of patients with MCD achieve a permanent nosuppressive agents some old (azathioprine, cyclophosphamide,
a protein/creatinine ratio of 1 or greater and ratios of 10 or greater remission but the remainder relapse. The relapses usually occur with chlorambucil) and some newer (cyclosporine, tacrolimus, mycophe-
are not uncommon in NS. common upper respiratory infections and may continue for years. nolate motetil, sirolimus) have been and are being used in conjunc-
Relapses are treated with prednisone as above but once urine tion with prednisone, but there is little control data in children for
2 History and physical examination provide important clues becomes negative for protein, prednisone is given as a single dose specific recommendations.
about the etiology of NS. Traditionally NS has been classified into every other morning and continued for 12 months and then tapered
primary or idiopathic and secondary types. Since the etiology in the gradually to zero over the subsequent 12 months. Once again, 10 ACE inhibitors and angiotensin II receptor antagonists can
primary type is not known, it is further classified based on histo- several schedules for the administration of prednisone exist but the be used in all NS associated with chronic glomerular diseases except
pathology into MCD, FSGS, MPGN, MGN and various proliferative superiority of any one schedule is not established. steroid-responsive MCD and/or PSGN for their renoprotective
glomerulonephritides including IgA nephropathy and RPGN. effects. Also, lipid-lowering drugs (statins) may be used in such
Secondary NS may result from infections (group A streptococci, 7 Patients who relapse frequently, i.e. 34 times/year, or who patients with chronic hyperlipidemia for their lipid lowering and
hepatitis B and C, HIV, infected ventriculoatrial shunts, syphilis, become steroid-dependent, i.e. require a certain dose of prednisone renoprotective effects.
malaria, etc.), vasculitis (SLE, HSP, Wegeners GN and polyarteritis), at all times to stay in remission, are prone to develop side effects of
systemic disorders (diabetes mellitus, amyloidosis), certain medi- prednisone (hypertension, cushigoid habitus, reduced bone mass, 11 NS associated with PSGN resolves on its own, and support-
cations (captopril, penicillamine, NSAIDs), and occasionally a stunting of height, mood changes, gastrointestinal bleeding, etc.). ive therapy is sufficient. Generally, progressive improvement over
neoplasm (Hodgkin lymphoma). Although MCD accounts for nearly These patients will generally achieve remission with the addition of days is seen in NS, hypertension and renal failure.
75% of all cases of NS in children, symptoms and signs associated cyclophosphamide (2.5 mg/kg) or chorambucil (0.15 mg/kg) given
with conditions producing secondary NS should be elicited during concurrently with the tapering down of prednisone. Blood counts 12 Patients with NS secondary to IgA nephropathy are occa-
history and examination. For example, antecedent of sore throat or are monitored weekly and the drug discontinued if the WBC count sionally treated additionally with fish oil (Max FPA) 24 g three times
impetigo with group A streptococci would suggest PSGN, and drops to ^3,500/l. Patients receiving cyclophosphamide can a day.
arthritis and facial rash would suggest SLE and a family history of develop alopecia and or hemorrhagic cystitis and should be encour-
Alport syndrome would suggest that as the diagnosis. Presence/ aged to drink plenty of fluids. Although these two drugs appear safe 13 Hepatitis-associated NS, particularly with MPGN or MGN
absence of hypertension provides an important clue. Blood pressure at the above-recommended doses, the long-term safety for gonadal histology, may resolve spontaneously. Patients in whom the renal
is normal in MCD but may be elevated in other entities. toxicity and possible future malignancy is not established and, disease does not resolve may be treated with interferon- or anti-
therefore, these drugs should only be used with the full consent of viral agents (lamivudine). HIV is treated with standard antiviral and
3 In the initial laboratory work-up, urine is tested for routine the patient. In children in whom cytotoxic drugs are to be avoided protease inhibitors.
protein/creatinine ratio and serum for electrolytes, creatinine, BUN, (puberty) or in those who continue to relapse, cyclosporine should
total proteins, albumin, cholesterol, C3 and C4, ANA, ASLO and be used. See previous section for details.
serology for hepatitis B, hepatitis C and HIV. In addition, a renal Selected reading
sonogram must be performed in every child with NS. These tests 8 Patients who continue to have proteinuria after a course of
establish the diagnosis, determine if renal failure (elevated serum 48 weeks of daily prednisone are considered steroid resistant. Eddy AA, Symons JM: Nephrotic syndrome in childhood.
creatinine) is present and provide useful information about the Some of these patients show a partial response in that the quantita- Lancet 2003;23:629639.
etiology of NS. tive proteinuria decreases and some improvement may also be Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J:
noted in serum albumin concentration and edema. Steroid-resistant Is there really an increase in non-minimal change nephrotic
4 Gross hematuria can occur with any of the glomerular NS showing MCD or FSGS on renal biopsies may also be treated syndrome in children? Am J Kidney Dis 2003;42:11071113.
diseases producing NS but is not seen in MCD. The gross hematuria with cyclophosphamide or chlorambucil, and some patients may Gipson DS, Gibson K, Gipson PE, Watkins S, Moxey-Mims M:
when seen is painless and brown tea colored. Microhematuria respond by going into a complete (urine negative for protein) or an Therapeutic approach to FSGS in children. Pediatr Nephrol
detected as occult blood on dipstick test or greater than 5 RBC/HPF incomplete (urine positive for protein but reduction of proteinuria 2007;22:2836.
on microscopic examination of urine sediment is almost always and improvement or resolution of edema) remission. Cyclosporine Grimbert P, Audard V, Remy P, Lang P, Sahali D: Recent
present at some time during the course of a glomerulonephritis and or tacrolimus may also achieve similar results in some patients; approaches to the pathogenesis of minimal-change nephrotic
13 however, the exact dosages and duration of treatment are not yet syndrome. Nephrol Dial Transplant 2003;18:245248.
may be present at onset in 1520% of patients with MCD. Persistent
microhematuria, however, is not usually seen in MCD. established. Doses of 150200 mg/m2/day or 46 mg/kg/day of Niaudet P: Steroid-resistant nephrotic syndrome in children; in
cyclosporine have been used successfully. Both cyclosporine and Avner ED, Harmon WE, Niaudet P (eds): Pediatric Nephrology, ed 5.
5 Prednisone is given daily in a single morning dose or 34 tacrolimus are nephrotoxic. In general, patients who show a partial Philadelphia, Lippincott-Williams & Wilkins, 2004, pp 557574.
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Glomerular and vascular disease S.P. Makker F. Santos Nephrotic syndrome in the child and adolescent
Glomerular and vascular disease S.P. Makker F. Santos Rapidly progressive glomerulonephritis
/0
Rapidly progressive glomerulonephritis
14 Renal biopsy
Immunofluorescence microscopy 1
Linear staining for IgG along the GBM 2 No staining or minimal staining 3 Granular staining along capillary loops
Negative staining for albumin and/or mesangium 4
Pauci-immune GN
Group A B-streptococci, ANA, C3, C4, ANCA
Anti-GBM disease
ANCA
Throat/skin culture (+) ANA (+), C3, C4 ANA (), C3m ANA ()
Lung hemorrhage (+) Lung hemorrhage () for group A B-streptococci mor N C4mor N C3, C4N
Anti-GBM Ab () Anti-GBM Ab ANCA (+) ANCA () ASLOM, anti-DNAaseBM ANCA () ANCA ()
Goodpasture syndrome Necrotizing glomerulonephritis Renal biopsy Renal biopsy Renal biopsy Renal biopsy
Wegener's granulomatosis consistent with consistent with consistent with consistent with
Churg-Strauss syndrome PSGN SLE MPGN IgAGN, HSP,
Miscoscopic polyangiitis Chronic GN
/
Chronic nephritic syndrome
16 History and examination 0
Laboratory tests 1
ds DNA Ab (+)
Alport syndrome SLE IgAGN MPGN Hep BsAg (+) Hep C ab (+) HIV (+)
Thin basement membrane disease HSP
Nail-patella syndrome MGN
Chronic GN
Hearing test Renal biopsy Renal biopsy Renal biopsy (types I, II, III) Renal biopsy
Ophthalmologic exam (WHO classification)
Bone film (in nail-patella syndrome)
Renal biopsy
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1 Chronic nephritic syndrome is defined as a 3 Initial laboratory tests to be obtained in all
Selected reading
clinical condition resulting from a chronic GN that con- patients with chronic GN are urinalysis including urine
sists of persistent hematuria, proteinuria and abnor- sediment examination, spot urine for protein/creati- Balow JE: Clinical presentation and monitoring of
mal cellular casts in urine sediment with or without nine ratio, serum electrolytes, BUN, creatinine, total lupus nephritis. Lupus 2005;14:2530.
accompanying hypertension and/or renal failure. He- protein, albumin, serum complement C3, C4, ANA, Barratt J, Feehally J: Treatment of IgA nephropathy.
maturia without proteinuria may be present in some ANCA and serologic tests for hepatitis B, hepatitis C Kidney Int 2006;69:19341938.
patients and occasionally (particularly in IgA nephrop- and HIV. Hematuria, proteinuria and RBC casts in the Bongers EM, Gubler MC, Knoers NV: Nail-patella
athy) the hematuria may be intermittent. Renal failure urine sediment essentially clinch the diagnosis of glo- syndrome: overview on clinical and molecular
may include the presence of edema and chronic ne- merulonephritis. If hereditary disorder is suspected findings. Pediatr Nephrol 2002;17:703712.
phritic syndrome may coexist with NS. (positive family history, hearing impairment, skeletal Kashtan CE: Familial hematurias: what we know and
pathology, etc.) and/or other etiologies are not appar- what we dont. Pediatr Nephrol 2005;20:10271035.
2 All entities other than MCD and FSGS listed ent, urines on all immediate family members should
in the algorithm for NS and those listed in the algo- be tested and hearing test, ophthalmologic examina-
rithm for RPGN can produce chronic nephritic syn- tion and bone film should be performed.
drome. Other conditions to be considered in the differ-
ential diagnosis of chronic GN include: Alport syn-
drome, thin basement membrane disease, nail-patella 4 For details on therapy, see Nephrotic syn-
syndrome, subacute bacterial endocarditis, hemolytic drome, Rapidly progressive glomerulonephritis, and
uremic syndrome, chronic renal transplant rejection, Acute nephritic syndrome.
other collagen vascular diseases besides SLE, and oth-
er infections such as filaria, leprosy and schistosomia-
sis. Symptoms and signs associated with the above
conditions and those mentioned in the NS algorithm
should be elicited during history and physical exami-
nation and would be helpful in guiding towards the
etiology. Painless gross hematuria (brown, tea color) is
common in chronic nephritic syndrome and is fre-
quently precipitated by upper respiratory infections
including a sore throat with group A streptococci.
A helpful feature differentiating chronic nephritic syn-
drome from acute PSGN is the fact that in chronic
nephritic syndrome the gross hematuria occurs in the
classic case at the time of sore throat but in PSGN it
occurs after a lag period of 12 weeks.
17
/
Vasculitis
Exclude systemic lupus erythematosus 0
Large vessel vasculitis Medium vessel vasculitis Small vessel vasculitis Other vasculitides ;
Angiography Cardiac US, angiography, skin biopsy Complement, ANCA, renal biopsy incl. IF
Stenoses of aorta Coronary artery Hepatic, renal Skin nodules Granulomatous Nongranulomatous
and branches aneurysm artery aneurysms
Takayasu arteritis 2 Kawasaki syndrome 3 PAN 4 CPA 5 Wegeners Churg-Strauss HSP 8 MPA 9 HUV :
granulomatosis 6 syndrome 7
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Glomerular and vascular disease W. Proesmans U.S. Alon Vasculitis
Glomerular and vascular disease W. Proesmans U.S. Alon Hemolytic uremic syndrome
/
Hemolytic uremic syndrome
20
Diarrhea 0 No diarrhea 3
S. dysenteriae Yersinia
EHEC Campylobacter
Pneumococci 5 HIV/AIDS 6 Cancer 7 Glomerulonephritis 8 Inf. ()
C. Freundii Salmonella
Cancer ()
GN ()
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Glomerular and vascular disease W. Proesmans U.S. Alon Hemolytic uremic syndrome
Urinary tract disease/tubulointerstitial nephropathy R. Adelman S. Hulton Urinary tract infection
Urinalysis 0
LE, nitrate negative LE, nitrate positive Pyuria Bacteriuria Bacteriuria and pyuria
Treatment Evaluation 6
Nonspecific pyuria
False negative
Trauma
Tuberculosis
Asymptomatic Uncomplicated UTI 3 Complicated UTI 4 Adjunctive U/S 7 VCUG 8 Radionuclide IVP :
/
Dilated/obstructed urinary tract
24 Abnormal US
VCUG
No Yes
No Yes
If severe, drainage
Prophylactic Repeat US Consider surgical relief 5 Suprapubic/urethral Prophylactic antibiotics Repeat US If severe, drainage
antibiotics 36 months 4 catheter drainage 36 months 4
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1 Dilatation of the urinary tract is considered 4 A dynamic renal scan using radiotracers such
Selected reading
when there is dilatation of the renal pelvis (hydrone- as MAG3 or DTPA in conjunction with a diuretic agent,
phrosis) with or without a dilated ureter. The clinical e.g. intravenous furosemide, is the preferred test to Belarmino JM, Kogan BA: Management of neonatal
features of a dilated/obstructed urinary tract depend investigate the dilated urinary tract. Estimation of hydronephrosis. Early Hum Dev 2006;82:914.
upon whether the obstruction is acute or chronic, drainage of the urinary tract and differential renal Fefer S, Ellsworth P: Prenatal hydronephrosis.
partial or complete, and on whether complications function will indicate the severity of the obstruction. Pediatr Clin North Am 2006;53:429447.
such as infection are present. The two commonest This scan, however, is best performed after the first Greenbaum LA, Mesrobian HG: Vesicoureteral
causes of dilatation of the urinary tract are VUR and month of life, when renal function is more mature. reflux. Pediatr Clin North Am 2006;53:413427.
obstruction. VUR presents usually with UTI or it can be Hubert KC, Palmer JS: Current diagnosis and
asymptomatic. A history of oligohydramnios (occa- 5 Causes of obstruction: management of fetal genitourinary abnormalities.
sionally polyhydramnios) during pregnancy may be Urol Clin North Am 2007;34:89101.
UPJ/UVJ obstruction Onen A, Jayanthi VR, Koff SA: Long-term follow up
noted. Acute obstruction usually presents with pain,
Intrinsic of prenatally detected severe bilateral newborn
depending on the site of the obstruction. Hematuria is
External compression hydronephrosis initially managed nonoperatively.
present when calculi are found. Hypertension can
Prolapsing ureterocoele (female) J Urol 2002;168:11181120.
occur in patients with acute obstruction. Polyuria due
Hydrocolpos (female) Piepsz A, Ham HR: Pediatric applications of renal
to the inability to concentrate the urine may result
Pelvic mass (e.g. Wilms tumor, abscess, nuclear medicine. Semin Nucl Med 2006;36:1635.
from acute bilateral partial obstruction.
ectopic kidney)
In chronic obstruction, a full bladder or enlarged kid-
UPJ obstruction is seen more commonly than UVJ
ney may be palpable. The inability to conserve sodium
obstruction.
is a common feature and may lead to salt wasting
and hyponatremia. In the case of severe obstruction, Bladder outlet obstruction
once satisfactory drainage has been established, it is Posterior urethral valves (male)
imperative to send the urine for culture and to treat Stone
infection aggressively. Monitoring of body weight, se- Rhabdomyosarcoma
rum electrolytes levels, acid base and fluid balance is Meatal polyp/stenosis
required. Hyperkalemic acidosis is commonly noted Prolapsed ureterocele
and close attention must be paid to postobstructive External compression
diuresis. Pelvic tumor
Spinal tumor
2 The management of a child with a dilated uri-
nary tract depends on the age of the child, the degree 6 If renal function is stable and the child is
of dilatation, the presence or absence of a dilated asymptomatic, observation of the child is appropriate.
ureter and whether there is a history of UTI. Age is an Progression of the hydronephrosis on ultrasound may
additional important factor in determining how to indicate a repeat diuretic renogram to demonstrate
proceed with the evaluation. In infants, females and, increasing obstruction.
in the case of UTI, a VCUG is usually the first test. In
older children, the degree of hydronephrosis and the 7 There is considerable debate about the indi-
parenchymal appearance dictates if a renal scan is cations for and timing of surgery for UPJ obstruction.
needed. Proponents of early surgery claim that pyeloplasty
should be performed before function is allowed to
3 DMSA radionuclide scan is the most reliable deteriorate. There is evidence, however, that many
test for detecting renal scars. The detection of renal neonates managed conservatively will demonstrate
scars is important because of the association between improvement in function without intervention.
unilateral and bilateral renal scars and the develop-
ment of hypertension and renal failure later in life. It is 8 Posterior urethral valves are the commonest
indicated in children with UTI and high-grade VUR and cause of lower urinary tract obstruction in male in-
25
if the renal US shows signs of renal injury (small or fants. 3040% of children presenting with posterior
hyperechogenic kidneys). urethral valves will also have renal dysplasia. Cystic
dysplastic changes in an individual kidney may be
associated with ipsilateral VUR.
Fetal hydronephrosis
26 Antenatal US /
US at 37 days
No reflux
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1 Most renal abnormalities are detected at 6 After ruling out VUR, radiotracers such as
Selected reading
1820 weeks. Persistent postnatal abnormalities are MAG3, DTPA or hippuran can be used to investigate
usually seen when the RPD is >6 mm at 20 weeks; the dilated urinary tract. Estimation of drainage of the Asku N, Yavascan O, Kangin M, Kara OD, Avdin Y,
>8 mm at 2030 weeks and >10 mm at >30 weeks of urinary tract and differential renal function will indi- Erdogan H,Tuncel TC, Cetinkaya E,Ozbay E,
gestation. While antenatal resolution of hydronephro- cate the severity of the obstruction. Re-ascent of the Sandikcioglu TG: Postnatal management of infants
sis may occur, the patient must still undergo postnatal radioactive agent from bladder to kidney may indirect- with antenatally detected hydronephrosis.
investigation as the hydronephrosis can recur. The ly suggest the presence of VUR. Unilateral renal func- Pediatr Nephrol 2005;20:12531259.
overall incidence of prenatal hydronephrosis is 1:100 tion <35% of total bilateral function suggests that the De Bruyn R, Gordon I: Postnatal investigation of fetal
to 1:500 of maternal-fetal US studies. kidney may be at risk of obstructive damage. Whether renal disease. Prenat Diagn 2001;21:984991.
such a kidney will benefit from early relief of obstruc- Ismaili K, Avni FE, Wissing KM, Hall M; Brussels
2 At birth, hydronephrosis is defined by a tion is still debated. Dynamic renal scan is best per- Free University Perinatal Nephrology Study Group:
RPD >5 mm. RPD 510 mm: mild hydronephrosis; RPD formed after the first month of life, when renal func- Long-term clinical outcome of infants with mild and
1020 mm: moderate hydronephrosis; RPD >20 mm: tion is more mature. moderate fetal pyelectasis: validation of neonatal
severe hydronephrosis. As much as 50% of renal ultrasound as a screening tool to detect significant
abnormalities detected in utero disappear after birth. 7 The obstruction of the urinary tract can be nephrouropathies. J Pediatr 2004;144:759765.
Obstructive and nonobstructive conditions can dilate located at the UPJ junction, the UVJ or in the urethra Lee RS, Cendron M, Kinnamon DD, Nguyen HT:
the urinary tract. Obstructive causes include: obstruc- (posterior urethral valves). Antenatal hydronephrosis as a predictor of
tion of the UPJ (45%) and of the UVJ (20%), posterior UPJ obstruction: Conservative management of UPJ postnatal outcome: a meta-analysis. Pediatrics
urethral valves (10%) or ureterocele/ureteral ectopia. anomalies is justified in most infants, provided that 2006;118:586593.
Nonobstructive causes include VUR (15%), transient the pelvic dilatation does not increase on repeated US, Martini S, Guignard JP: Diagnostic et prise en
hydronephrosis and physiological hydronephrosis. and that on isotopic studies the relative function of the charge des dilatations des voies urinaires dpistes
affected kidney does not deteriorate. The indication in intero. Rev Med Suisse Rom 2002;122:619624.
3 Prophylaxis should be started if significant and the best time for pyeloplasty remains ill-defined. Woodward M, Frank D: Postnatal management of
hydronephrosis (RPD >10 mm) is seen on renal US. UVJ obstruction: Megaureters are the results of abnor- antenatal hydronephrosis. BJU Int 2002;89:149156.
Drugs commonly used include: mal or dysfunctional UVJ. Spontaneous improvement
First month of life: of megaureters is common, so that conservative
amoxycillin 1030 mg/kg/day (in 2 doses) management is recommended when renal function
16 months: and dilatation remains stable. Ureteric reimplantation
cotrimoxazole 34 mg/kg/day (in 2 doses) may be performed when dilatation increases and
>6 months: renal function deteriorates.
nitrofurantoin 2 mg/kg/day (in 2 doses) or Posterior urethral valves: The most common cause of
cotrimoxazole as above congenital bladder outlet obstruction, occurring only
in males; its incidence is approximately 1:8,000. The
4 Whether to recommend VCUG in all infants bladder outlet obstruction leads to a trabeculated,
with persistent postnatal hydronephrosis remains thick-walled bladder, and to damage to the renal
controversial. We recommend performing a VCUG in parenchyma. Clinical presentation can range from
these conditions: RPD above 10 mm, significant ante- severe obstruction in utero leading to fetal demise, to
natal hydronephrosis, a thick-walled bladder or ure- hydronephrosis with normal kidney function diag-
teric dilatation, and in cases of bilateral hydronephro- nosed in late childhood. Transurethral incision of the
sis. valves is the treatment of choice.
Ureterocele: Occurs in 1:5,000 neonates with M:F ratio
5 VUR is detected postnatally in ~10% of neo- of 1:35. Ureteroceles are frequently associated with
nates with antenatal hydronephrosis. VUR is most duplicated collecting system (8090%), are bilateral in
severe and most frequent in males (34 M:1 F). In 1020% of patients, and associated with ectopic inser-
males, renal scarring (dysgenesis) is often present at tion of the ureter into bladder in up to 75% of cases.
birth. In patients with VUR, antibiotic prophylaxis A large ureterocele may result in bilateral ureteral
27 should be continued as well as serial renal sonogram obstruction. Transurethral endoscopic punction of the
follow-up. For further details, see appropriate algo- ureterocele is often used as an initial intervention.
rithm.
/
Vesicourethral reflux
28
Evaluation 0 Treatment 2
Negative Positive
/
Dysfunctional voiding
30
Detailed voiding history and Physical examination 2 Urine dipstix
Clinical history 0
3-day-frequency voiding diary 1 Serum creatinine
Renal US
VCUG IVP Pelvic floor exercises U/S (renal/bladder) and Laxatives A -Blocker
urodynamic flow rates 6 No (Prazocin) <
Response
Non-neuropathic Intermittent bladder
neuropathic bladder catheterization
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1 Enuresis is defined as normal voiding, occurring at an inap- or more than 10% of the normal bladder capacity for age. Noninva- 15 Non-neuropathic bladder (Hinman syndrome) represents
propriate time, or involuntarily in a socially unacceptable setting. sive urodynamics, using a graphic recording of urinary flow rate dur- the extreme of the spectrum and will only be diagnosed by exclusion
Enuresis is most commonly nocturnal, although it is not uncommon ing voiding, is becoming a more standard office procedure. Flow pat- of all other identifiable treatable conditions. MRI scanning of the lum-
for nocturnal enuretics to have episodes of diurnal enuresis. terns and rates need to be consistent to allow for appropriate evalua- bar spine is necessary to exclude an underlying undiagnosed neuro-
Diurnal enuresis is usually linked with the term dysfunctional voiding tion and sometimes several recordings are necessary. Invasive proce- logical disorder. In Hinman syndrome there is no physical neurologi-
which can be categorised into neuropathic and non-neuropathic dures should only be done following the results of the noninvasive cal deficit; however, the bladder behaves in a neuropathic fashion.
voiding disorders. Functional neuropathic voiding disorders include tests where there is a suspicion of a neuropathic bladder sphincter This occurs primarily in boys as an acquired voiding disorder charac-
spina bifida, transverse myelitis and spinal cord trauma. This review dysfunction and should only be performed in specialist centers. terised by inappropriate voluntary contraction of the striated urinary
focuses on the non-neuropathic voiding dysfunction. sphincter during the process of micturition. This results in functional
9 Common between 5 and 7 years of age, present with urinary obstruction that over time is associated with urinary tract
2 The majority of children have acquired an adult voiding pat- hyperactivity or instability of the bladder, with urgency and small infection, myogenic bladder failure, hydronephrosis and even renal
tern by 45 years of age and investigations for dysfunctional voiding frequent voids. This may follow an initial episode of painful voiding, insufficiency. Ochoa syndrome has the same clinical features at
should not be undertaken in children under 5 years. e.g. following UTI or urethritis. Hinman syndrome but is known as urofacial syndrome because of
facial grimace instead of smile and is inherited in an autosomal-dom-
3 The 3-day frequency voiding diary is particularly helpful to 10 Characterized by large capacity hypotonic bladder with inant pattern. If the patient is not found to have Hinman syndrome
provide more detailed information about the childs voiding pattern. infrequent voiding every 812 h and incontinence between voiding. but is still not responding to treatment one must consider other con-
The information does not have to cover consecutive days, and week- Sensation of bladder fullness is reduced. Incontinence is due to ditions such as congenital bladder neck insufficiency or ectopic ure-
ends may give better opportunity for the parent to document the overflow and the urinary stream is poor with incomplete voiding. teroceles.
information. The diary must include the record of bowel action. Such bladder decompensation may occur as a result of previous
posterior urethral valves in infancy and can be associated with 16 The management of constipation is imperative in all
4 Inspection of the genitalia in boys should exclude a meatal myogenic detrusor failure. patients. It is due to the inability to relax the pelvic floor musculature.
stenosis and in girls look for labial adhesions, which can impede
urinary flow. Voiding dysfunction and urinary symptoms have been 11 Bladder training involves frequent voiding, initially 2 hourly, * Primary nocturnal enuresis is a prevalent disorder with a complex mode of
inheritance. It appears to be associated with a deficiency of inhibitory signal
described with sexual abuse and attention needs to be directed later 4 hourly on a regular basis with advice to relax the pelvic floor
processing in the brain stem which underlies the deficient pre-path inhibition of
towards examination of the genitalia for any scarring, tearing or when voiding, e.g. by whistling. Low-dose prophylactic antibiotics micturition, as well as the inability to inhibit micturition at night. A low nocturnal
signs of trauma. This obviously needs to be performed carefully and are useful in children who have a history of urinary tract infections arginine vasopressin production may be present, and the role of melatonin in this,
sensitively. without reflux. The antibiotics can be used for a short period of time, as well as the regulation of sleep/wake cycle, is currently under review. These
usually not longer than 6 months. children may respond to Desmopressin (DDAVP 2040 g intranasally). This
should not be used for prolonged periods as water intoxication is a serious
5 Children with dysfunctional voiding are at risk of recurrent
adverse side effect. DDAVP should be used along with other treatment modalities,
UTIs. Both reflux and UTIs are observed in 3040% of children at the 12 Oxybutynin is the most commonly used anti-cholinergic
such as bed wetting alarms, dry bed training and behavioural treatment. It is
time of dysfunctional voiding and resolve with the attainment of a drug. It is usually initiated at a low dose once or twice daily and is important to distinguish nocturnal enuresis from diurnal enuresis or daytime
normal voiding pattern. Bladder instability with high intravesical gradually titrated to a maximum dose over 68 weeks. Side effects wetting. It is not uncommon for bed wetters to wet their underclothes during the
pressures are observed in children with VUR. High voiding detrusor are common and include facial flushing, constipation and dry mouth. day or for day wetters to wet the bed. They should be viewed as two separate
problems. Diurnal enuresis is linked with the term dysfunctional voiding.
pressures have also been observed in infants presenting with symp- Occasionally headache and palpitations are reported. Approximately
Dysfunctional voiders exhibit poor co-ordination between the bladder and
tomatic urinary tract infections who do not have VUR. 20% of patients have to stop medication because of these side bladder outlet which results in inefficient bladder emptying and is termed
effects. The management of constipation is essential and needs dyssynergia.
6 A history of continuous urinary incontinence, particularly in particular vigilance in patients on anticholinergic treatment.
a young girl, is suggestive of an ectopic ureter. If intravenous uro-
gram fails to demonstrate this, careful examination of the introitus by 13 Biofeedback training is very useful in children over 8 years
Selected reading
a trained urologist may identify the opening of the ectopic ureter. of age. This involves psychological support, learning to void using
a flowmeter, ultrasound scanning to check for complete bladder Akbal C, Genc Y, Burgu B, Ozden E, Tekgul S: Dysfunctional voiding
7 Giggling and laughter associated with embarrassing wet- emptying, the use of alarms to detect wetness and regular charting and incontinence scoring system: quantitative evaluation of incon-
ting episodes is more commonly seen in girls and is usually self-lim- of voiding activities. Follow-up by a dedicated incontinence adviser tinence symptoms in pediatric population. Urol 2005;173:969973.
iting. Anticholinergic agents may be helpful. Postvoid dribbling may is essential. Such behavior modification programmes will cure 50% Austen PF, Ritchey ML: Dysfunctional voiding. Paediatr Rev
occur in girls (commonly obese) where the urine accumulates in the of children within 6 months and 75% within 1 year. Pharmacological 2000;21:336340.
lower vagina. intervention may speed up this process for some patients but good Feldman AS, Bauer SB: Diagnosis and management of dysfunc-
31 voiding behavior is the key to success. tional voiding. Curr Opin Pediatr 2006;18:139147.
8 US is very useful to image the upper urinary tract to demon- Nrgaard JP, van Gool JD, Hjalmas K, Djurhuus JC: Standardiza-
strate abnormalities such as duplex kidney, dilatation of the collecting 14 Alpha-adrenergic blockade may be useful to improve tion and definitions in lower urinary tract dysfunction in children.
system and gross reflux. A thickened bladder wall with trabeculation bladder emptying in some patients. Prazosin or Doxazosin 0.451 mg Br J Urol 1998;81(suppl 3):116.
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Urinary tract disease/tubulointerstitial nephropathy S. Hulton R. Adelman Dysfunctional voiding
Urinary tract disease/tubulointerstitial nephropathy J. Smith F.B. Stapleton Loin pain with hematuria
/
Loin pain with hematuria
32 History and physical examination
Urinalysis
Red blood cells White blood cells Red blood cell casts Crystals Blood tests including Renal angiogram
No casts Bacteria Protein electrolytes, calcium, BUN,
Urine culture creatinine, blood gases
Normal Abnormal
Pyelonephritis Glomerulonephritis Consider urolithiasis Renal arteriovenous fistula
Normal Abnormal Nutcracker syndrome
Ultrasound of kidneys and bladder with Doppler 0 Glomerulopathy
(e.g. IgA nephropathy)
Hypercalcemia
(e.g. hyperparathyroidism) Renal biopsy 4
Normal Abnormal Renal tubular acidosis
Urolithiasis
Obstructive uropathy
Polycystic kidney disease Normal Abnormal
Pyelonephritis Intravenous pyelogram 2 Glomerulopathy
Renal vein thrombosis (e.g. IgA nephropathy)
Tumor Thin basement membrane disease
Nutcracker syndrome
Normal Abnormal
Medullary sponge kidney
Tumor
Further urine evaluation 1 Cyst Loin pain hematuria syndrome 5
24-hour collection of calcium, protein, sodium, citrate,
cystine, oxalate, uric acid, creatinine
Cystoscopy 3
Normal Abnormal
Proteinuria
Hypercalciuria Normal Abnormal Psychiatric evaluation 6
Hypocitraturia Bladder lesion
Cystinuria
Hyperoxaluria
33
/01
Renal trauma
34
Gross hematuria or microscopic hematuria with No gross hematuria or microscopic hematuria with
RBC >20/HPF RBC <20/HPF
CT scan 2
(usually CT angio)
35
/
Tubulointerstitial nephritis
36 Renal insufficiency/ failure
Tubular dysfunction
Therapy 5
/
Single kidney (renal agenesis)
38
Association of nonurological malformations 0
Clinical evaluation 1
US 2
VCUG 3
DMSA renal scan 4
39
/
Renal hypoplasia-dysplasia
40 Assessment of renal function 0
US
VCUG
DMSA renal scan
Nephrological follow-up
41
/
Nephromegaly
42
Normal/minor anomaly Pathological Pseudoenlargement, transient nephromegaly 1
Physiological response 0
US, MAG-3 diuretic scan, US, CT, syndromic Specific labs Urinalysis, culture, CBC, smear, Radiographic study; Specific syndromes,
VCUG, CT, cystoscopy, IVP findings, tissue CBC, urine eosinophils, Hb electrophoresis, bone marrow or tissue, history, labs
Urine-pigmented casts, urinary protein, bone marrow, tissue for diagnosis
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1 Nephromegaly is noted by palpation of an abdominal/flank 5 ARPKD may present in utero with large, hyperechoic kidneys, scess). Nephromegaly is usually not palpable and resolves about 2
mass or by radiographic study. The degree of renomegaly is unrelated oligohydramnios, no bladder visualization and negative family history. weeks after starting therapy. In renal malakoplakia/xanthogranuloma-
to disease severity, histological pattern or prognosis. History and phys- Most affected children progress to renal failure in childhood, but mild tous pyelonephritis, a form of chronic interstitial nephritis, patients
ical examination with laboratory and radiological studies may allow disease can be undiagnosed for years. Neonatal ADPKD can cause have recurrent UTI, sometimes massive renomegaly and a non-func-
diagnosis without biopsy/surgery. large, hyperechoic kidneys with/without visible cysts. Cysts may ini- tioning avascular mass. Destroyed renal parenchyma is replaced by
tially be unilateral. Patients can be asymptomatic early in the disease yellowish-brown soft infiltrate of bacteria, inflammatory cells, lipid-lad-
2 Renomegaly from renal hypertrophy occurs in response to with cysts noted on US performed because a parent is affected. Cysts en histiocytes and calculi. The lesion resembles malignancy and histo-
congenital/acquired solitary kidney or unilateral reduction in renal may present as abdominal pain, mass, hematuria, hypertension or UTI. logical diagnosis is needed. ATN, toxic or hypoxic, often causes reno-
function. Hypertrophy starts minutes after loss of a healthy kidney and Extrarenal problems include mitral valve prolapse, cysts in liver, ovary, megaly. By contrast, hypoxic injury causes acute cortical necrosis and
takes months to complete. Benign nephromegaly includes duplex kid- spleen and pancreas, hernias and cerebral aneurysms. MCDK, a severe renal infarction does not. This may relate to ongoing renal arterial flow
ney seen on abdominal US or CT. Two benign conditions may resemble renal dysgenesis, is the most common cause of neonatal abdominal during tubular necrosis whereas severe arterial compromise sufficient
a mass. Palpable persistent fetal lobulation in a child is clarified by US. mass. The MCDK has an atretic or non patent ureter and no identifiable to necrose glomeruli is associated with reduced renal blood flow. Cell
A prominent Bertin column is differentiated from tumor by US (with renal sinus or functioning renal parenchyma. Contralateral anomalies, swelling and consequent renomegaly are unlikely if blood flow is insuf-
agents to enhance vascularity) or CT. e.g. VUR, UPJ obstruction, are common. VCUG and nuclear scan can ficient to deliver more fluid into the kidney.
confirm lack of VUR and function. Tuberous sclerosis (autosomal-domi-
3 Pseudo-renal enlargement may reflect splenic left renal com- nant neurocutaneous hamartomatosis) affects skin, heart, retina, cen- 8 Sickle cell disease may induce renomegaly by sickling of red
pression, posterior pararenal mass, perirenal hematoma or urinoma. tral nervous system and kidney. Renal lesions include angiomyolipo- blood cells, oxidative stress, medullary congestion and vaso-occlusive
Traumatic intra-/extrarenal hematoma and traumatic/obstructive urin- mas (~50% of patients) that are often bilateral and best evaluated with disease. A similar process may occur in thalassemia. RVT causes neph-
oma are seen by US or CT. Transient renomegaly may follow angio- CT, and large cysts (~20% of patients) resembling ADPKD. GCKD in- romegaly and gross hematuria. In older nephrotic children, CT may
plasty for renal artery stenosis or ESWL and occurs with sarcoid granu- cludes entities with glomerular (not tubular) cysts that are typically di- show renal vein or inferior vena caval thrombus, pericapsular venous
lomatous infiltration that distorts renal contour and mimics tumor. A lated Bowmans capsules with an aborted/primitive glomerulus. Cysts collaterals or opacification of renal parenchyma. In neonates or older
notable cause in neonates/older children, Tamm-Horsfall proteinuria, are cortical, not medullary, in contrast to other cystic diseases. Infants infants, look for diffusely enlarged, hyperechoic kidneys with ill-de-
may present as renal masses. US shows large, hyperechoic kidneys may have abdominal masses (cystic kidneys by US) and renal insuf- fined central-echo complexes and poor venous Doppler flow. Inferior
resembling ARPKD, RVT, dysplasia or intrarenal obstruction. Oliguria ficiency. Mild disease can present later in life with hypertension or flank vena caval or main renal vein thrombus is usually absent.
and ARF may occur, but usually reverse in a few days or weeks. pain.
9 Wilms tumor (nephroblastoma) is the most common tumor
4 Urinary tract obstruction may present as a flank/abdominal 6 In diabetes mellitus, renomegaly becomes prominent in pu- causing renomegaly in children. Work-up includes laboratory data, US,
mass or distended bladder in infancy or may be found at evaluation of berty, especially with reduced renal function. Glomerular hypertrophy, chest film, skeletal survey, abdominal/chest CT. Radiological study may
UTI, abdominal/flank pain or hematuria. UPJ obstruction, the most proximal tubular hyperplasia and hypertrophy may relate to increased miss contralateral renal tumors and renal surgical exploration may be
common cause of hydronephrosis/renomegaly in newborns, can be growth hormone and insulin-like growth factor. Careful glycemic con- needed. Nephroblastomatosis (residual metanephrogenic tissue in a
seen antenatally by US, can present as an abdominal mass and often trol reduces renal hyperfiltration and high GFR, but may not reduce mature kidney) causes renomegaly. This can regress to fibrous tissue,
resolves spontaneously in 612 months. Other causes of hydronephro- renomegaly. Glycogen storage disease type 1 can present at 34 mature to glomeruli and tubules, or become malignant (e.g. Wilms tu-
sis/renomegaly include UVJ obstruction, VUR and PUV. PUV, mucosal months of age with hepatomegaly or hypoglycemic seizures when mor), but the usual course of nephroblastomatosis is regression before
cusps that appose during voiding, can obstruct urine flow. If mild, they food intake decreases (acute illness or night feeding is stopped). Renal malignancy. Other renal tumors are usually unilateral and solid. Con-
may present after many years with incontinence, polyuria, nocturia or problems include renomegaly from accumulated glycogen, hyperfiltra- genital mesoblastic nephroma (leiomyomatous hamartoma) is usually
UTI. If severe, infants have an enlarged, trabeculated bladder, weak tion, proteinuria, FSGS, nephrocalcinosis, stones and Fanconi-like syn- benign and tends to present in infants <3 months of age. Neuroblas-
stream, renal dysplasia, severe hydronephrosis and hydroureter (not drome. Hereditary tyrosinemia type 1 causes liver and renal tubular toma is usually solid, may have calcifications or cysts and must be dif-
always bilateral) and may have urosepsis. Diagnosis is best made by dysfunction with renomegaly and uniform thickness of renal cortex. ferentiated from primary renal tumor. Clear-cell sarcoma typically pres-
VCUG. If hydroureter/nephrosis is unilateral, check for urethral obstruc- Fabrys disease shows nephromegaly in the 3rd decade from accumu- ents in a 3- to 5-year-old child, tends to metastasize to bone and brain
tion as well as high ureteral lesions with IVP or antegrade pyelogram. lation of glycosphingolipid. Acromegaly causes nephromegaly prob- and has a poor prognosis. Work-up includes brain MRI, bone scan, skel-
In Prune-Belly syndrome (mostly in males), in utero prostatic urethral ably from increased tubule mass rather than increased glomerular size. etal survey and abdominal/chest CT. Malignant rhabdoid tumor is usu-
obstruction or urethral hypoplasia may be causative in many cases. Other causes of renomegaly include Perlman, Sjogren, Beckwith- ally large, originates in the central hilar area, replaces the whole kidney,
Features include oligohydramnios, hydronephrosis, renomegaly, di- Wiedemann syndromes, renal amyloidosis, intravenous hyperalimen- metastasizes to lung, brain, liver and has median presenting age at
lated prostatic urethra and ureters, VUR, bilateral cryptorchidism, lax/ tation/protein loading (usually bilateral and reversible) and in convales- around 11 months. Abdominal and chest CT and brain MRI are needed.
wrinkled nonresistant abdominal wall (hypoplastic lower abdominal cent burn patients, perhaps from higher renal workload (high therapeu- Multilocular cystic nephroma usually presents from 3 to 24 months of
muscles) and renal dysplasia and is suspected by finding cystomegaly tic salt/fluid/protein intake and catabolism). age as benign multilocular cyst or as cystic lesion with stroma contain-
on US as early as 1214 weeks gestation. Nephrolithiasis is the most ing partially differentiated blastema cells. The latter may have Wilms
43 common acquired cause of childhood hydronephrosis/renomegaly. 7 Nephromegaly may occur with acute postinfectious or vascu- tumor nodules and is indistinguishable from cystic Wilms tumor with-
Intrarenal obstruction with no hydronephrosis occurs when pigmented litic glomerulonephritis (can be unilateral with flank pain) and with NS out biopsy. Hematologic malignancies, e.g. acute lymphoblastic leuke-
casts/crystals occlude tubule lumens. With dehydration and acidic (with no relation to histology or steroid response). Loin pain may relate mia or lymphoma, cause diffuse unilateral or bilateral nephromegaly
urine, hemoglobinuria/myoglobinuria and hyperuricosuria can cause to fluid retention and a response to diuretics often relieves pain. Pa- from renal infiltration or discrete intrarenal/hilar mass lesions. Rare
ARF and large, echoic kidneys, resembling ARPKD, RVT or dysplasia, tients with acute TIN typically have renal tenderness, pyuria, urinary causes of renomegaly include renal adenomatosis, histiocytic medul-
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Structural/congenital abnormalities M.A. Linshaw G. Rizzoni Nephromegaly
Structural/congenital abnormalities M.A. Linshaw G. Rizzoni Hyperechoic kidney
/
Hyperechoic kidney
44
Cortical 0 Medullary 0
Cystic kidney diseases Chronic renal failure Pyelonephritis Hypercalciuria Cushing syndrome 6
Interstitial nephritis Nephronophthisis Tumors Hyperoxaluria Corticosteroid therapy
Acute tubular necrosis Dysplasia with hypoplasia Xanthinuria Fat deposition
Acute glomerulonephritis Ischemia Medullary sponge kidney Renal candidiasis
Nephrotic syndrome Cortical necrosis Vascular congestion
Malignancy Chronic glomerulonephritis Urate nephropathy
Infections Tamm-Horsfall protein precipitation
Metabolic storage diseases
Renal vein thrombosis
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Structural/congenital abnormalities M.A. Linshaw G. Rizzoni Hyperechoic kidney
Structural/congenital abnormalities G. Rizzoni M.A. Linshaw Cystic kidneys
/
Cystic kidneys
46
Polycystic kidney disease 0 Glomerulocystic kidney disease 3 Hereditary Medullary cystic disease
malformation syndrome 6
Autosomal-dominant Autosomal-recessive Non syndromal 4 With malformation syndrome 5 Juvenile nephronophthisis Medullary sponge
polycystic kidney disease 1 polycystic kidney disease 2 Medullary cystic disease 7 kidney 8
/
Renal mass
48
Normal/physiological 0 Fluid collection, infection 1 Renal anomaly Renal anomaly Tumor 4 Cystic lesion 5
no hydronephrosis 2 hydronephrosis 3
Prominent fetal lobulation Abscess (intrarenal/extrarenal) Duplex kidney UPJ obstruction Wilms ARPKD
Column of Bertin Hematoma Horseshoe kidney UVJ obstruction Mesoblastic nephroma ADPKD
Renal hypertrophy Urinoma Pelvic kidney PUV Malignant rhabdoid MCDK
Xanthogranulomatous/ Crossed, ectopia Prune-belly syndrome Clear-cell sarcoma Cystic nephroma
renal malakoplakia Angiomyolipoma GCKD
Renal cell carcinoma Lymphangiectasis
Confirm: US or CT US, CT, culture, antibiotics, Abdominal CT; US, VCUG, MAG-3 diuretic Radiographic study; Abdominal CT, DMSA
surgery, fluid (creatinine), nuclide scan to confirm and DMSA scans, CT abdomen/chest, scan for function, tissue
tissue, observation as needed ectopic kidney; VCUG for UTI antegrade pyelogram; brain MRI, abdominal US, for accurate diagnosis
or later hydronephrosis cystoscopy, IVP IVP, bone scan skeletal survey;
/0
Neonatal hypertension
50 Clinical Features
Congenital Thromboembolism Coarctation of aorta Congenital adrenal Glucocorticoids Pain Wilms tumor TPN
PKD (AD, AR) Renal artery stenosis BPD hyperplasia Theophylline Elevated intracranial Mesoblastic Hypercalcemia
MCDK Mid-aortic coarctation Hyperthyroidism Caffeine pressure (intracranial nephroma Postclosure of
Obstructive uropathy RVT Gordon syndrome Vitamin D intoxication hemorrhage, Neuroblastoma abdominal wall defect
Acquired Congenital rubella syndrome Maternal drug abuse hydrocephalus, etc.) ECMO
Acute tubular necrosis (cocaine, heroin) Seizures
Hydralazine vasodilator bolus: 0.150.6 mg/kg i.v. bolus or tachycardia frequent side effect;
5 Various drugs may cause hypertension in (arteriolar) per dose infusion must administer q 4 h when given i.v. bolus
neonates, either by direct administration to the sick drip: 0.755.0 g/kg
neonate (glucocorticoids, theophylline), or due to per min
maternal drug abuse that leads to hypertension in their
Labetalol - and -blocker 1.203.0 mg/kg per h i.v. bolus or heart failure, BPD relative contraindications
infant child (e.g. heroin, cocaine).
constant infusion
51
6 A common cause of hypertension in prema- Nicardipine Ca2+ channel blocker 13 g/kg per min constant infusion may cause reflex tachycardia
ture infants is intracranial hemorrhage.
Sodium vasodilator 0.510 g/kg per min constant infusion thiocyanate toxicity can occur with
/0
Pediatric hypertension
Evaluation 1
52
Renal sonogram PRA Serum: aldosterone, cortisol, ECG, Echocardiogram Fundus examination Positive family Hx
Voiding cystourethrography Renal Doppler sonogram PRA, TSH, FT4 Cardiac catheterization Brain CT/MRI Normal physical examination
Renal nuclear scan CT angio./angiography Urine: cathecholamines, cortisol Lumbar puncture and workup
(DTPA/MAG-3, DMSA) Imaging: abdominal sonogram,
Renal biopsy MIBG scan
PRAM
Anatomic malformations RVT Low plasma renin Coarctation of aorta Brain trauma Glucocorticoids Positive genetic analysis
Reflux/obstructive Renal artery stenosis Cushing syndrome Brain tumor Vitamin D (in selected cases)
nephropathy (fibromuscular dysplasia, Primary hyperaldosteronism CNS bleeding Cyclosporin A
Renal trauma neurofibromatosis, etc.) Liddle syndrome Pseudotumor cerebri Oral contraceptives
Renal tumors Umbilical artery catheter Gordon syndrome Guillain-Barr syndrome Sympathomimetics
No anatomic malformations (in neonate) Apparent mineralocorticoid excess Familial dysautonomia Amphetamines
Pyelonephritis Takayasu arteritis Glucocorticoid-remediable aldosteronism Cocaine
Hemolytic-uremic syndrome Moyamoya disease Congenital adrenal hyperplasia Heavy metal poisoning
Glomerulonephritides (hypertensive forms)
Vasculitides Normal plasma renin
Pheochromcytoma
Hyperthyroidism
Hypercalcemia
/
Aminoaciduria
54
Fanconi syndrome Inborn errors of Classic cystinuria (types I, II, III) Hartnup disease Imminoglycinuria Dicarboxylic AA
Prematurity amino acid metabolism Lysinuric protein intolerance Methioninuria Isolated glycinuria
Isolated cystinuria Histidinuria
Hyperdibasic AA type I
Isolated lysinuria
/
Cystinuria
(hexagonal crystals in urine; urine cystine >100 mol/g creatinine)
56
Nephrolithiasis 2
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1 Children with cystinuria may be identified in inherited two mutant SLC3A1 genes. Both types of
Selected reading
screening programs, during evaluation of familial cystinuria have a high risk of recurrent nephrolithiasis
nephrolithiasis or when they present with renal calculi. and usually excrete cystine in the range of 2,5005,000 Goodyer PR, Saadi J, Ong P, Elkas G, Rozen R:
The incidence of cystinuria worldwide is estimated to mol/g creatinine. High fluid intake (about 2.5 l/m2) Cystinuria subtype and the rest of nephrolithiasis.
be about 1:10,000 but may be higher in specific popu- should be advised; this can be individualized by mea- Kidney Int 1998;54:5661.
lations (1:2,000 among newborns in England, 1:2,500 suring the amount of cystine excreted per day and cal- International Cystinuria Consortium: Functional
in Libyan Jews). Normally, >98% of filtered amino culating the amount of fluid needed to dilute the cys- analysis of mutations in SLC7A9, and genotype/
acids is reabsorbed by transport mechanisms in the tine to <1,200 mol/l. Patients who frequently exceed phenotype correlation in non-type I cystinuria.
luminal membrane of proximal tubular cells. However, this theoretic limit of urinary cystine solubility in acidic Hum Mol Genet 2001;10:305316.
in patients who inherit one or more of the cystinuria urine should take 0.52.0 mEq/kg/day of NaHCO3 or Palacin M, Goodyer P, Nunes V, Gasparini P:
genes, the specific transport mechanism shared by potassium citrate to bring urine pH to >7.5, especially Cystinuria; in Scriver C, Beaudet A, Sly W, Valle D
cystine, artinine, ornithine and lysine is defective. The overnight when urine is most concentrated and acidic. (eds): The Metabolic and Molecular Basis of
only clinical consequence is cystine nephrolithiasis. Yearly ulrasonography is warranted after age 5 years. Inherited Disease. New York, McGraw-Hill, 2001,
Cystinuria should be distinguished from a broader On the other hand, children who inherit one recessive vol III, pp 49094932.
Fanconi pattern of aminoaciduria, accompanied and one dominant gene from their parents have the Rogers A, Kalakish S, Desai RA, Assimos DG:
by variable degrees of glucosuria, proteinuria and mixed type of cystinuria and have much lower risk of Management of cystinuria. Urol Clin North Am
phosphaturia. stone formation, requiring less intense monitoring. 2007;34:347362.
Zelikovic I: Aminoaciduria and glycosuria; in
2 At birth, renal tubular reabsorption of amino 4 Pure cystine calculi are radio-opaque and Avner ED, Harmon WE, Niaudet P (eds): Pediatric
acids is not fully mature. There is little effect on nor- often incorporate variable amounts of calcium; they Nephrology, ed 5. Philadelphia, Lippincott
mal infants but children who are carriers of one par- may be identified by ordinary radiography or by ultra- Williams & Wilkins, 2004, pp 701728.
tially dominant (type II or type III) cystinuria gene may sonography. About 4050% of stones recovered from
excrete cystine at exaggerated levels, appearing to be cystinuria patients contain substantial amounts of
homozygotes. Final diagnosis should be delayed; calcium. Prior to starting an alkalinizing agent, hyper-
urine cystine quantification should be repeated at calciuria should be ruled out. Individual risk of nephro-
about 2 years of age. lithiasis cannot be predicted by urine cystine level
alone. If multiple or obstructive stones are identified,
3 Cystinuria has now been attributed to two cystine chelating agents such as MPG (1015 mg/kg/
principal genes. SLC 7A9 encodes the luminal cystine day) or penicillamine (30 mg/kg/day) may be intro-
transporter, itself, and is transmitted as a dominant duced, monitoring carefully for side effects such as
urinary phenotype. If both parents excrete cystine fever, rash, elevation of liver enzymes and proteinuria.
above the normal range (>100 mol/g creatinine), but Partial dissolution may allow the stone to pass, but
less than the stone-forming range (>1,200 mol/g cre- most will require lithotripsy or surgical stone removal.
atinine), the child has inherited two dominant SLC 7A9 Long-term prophylaxis with these agents (vs. high
mutations. By contrast, the SLC3A1 gene encodes a fluid intake plus urinary alkalinization) should be indi-
subunit of the transporter and is transmitted as a vidualized based on compliance, drug tolerance and
recessive urinary phenotype. If both parents excrete severity of recurrent stone disease.
cystine in the normal range, the child has most likely
57
/
Glycosuria
58
59
/
Renal tubular acidosis
60 History and physical examination 0
Serum creatinine, Na+, K+, Ca2+, P, HCO3, plasma aldosterone, renin
Urine-urinalysis, osmolarity, Cl, Na+, K+, Ca2+, pH
Renal US
Hypokalemia Hyperkalemia
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1 The kidney is the major organ responsible for acid-base transporters leading to primary isolated RTA have been recognized sterone biosynthesis called CMO deficiency types I and II. Adrenal
homeostasis. This homeostasis is maintained by the renal tubule in in the last years. Autosomal-recessive PRTA associated with ocular cortical failure is observed in Addison disease and in adrenoleuko-
two ways: (1) reabsorption of the filtered HCO 3 (mainly by the proxi- abnormalities, short stature and mental retardation is caused by a dystrophy, which is very rare in children.
mal tubule), and (2) excretion of the H+ produced by the human body genetic defect in the Na+/HCO 3 cotransporter NBC1 located in the Hyporeninemic hypoaldosteronism is observed in patients with dia-
in the distal tubule. When one of these processes is defected RTA basolateral membrane of the proximal tubular cell. An additional betic nephropathy or chronic tubolointerstitial disorders. Although
ensues. There are 3 major types of RTA: type 1 (DRTA), type 2 (PRTA) entity leading to autosomal-recessive PRTA and osteopetrosis is due considered rare in children, hyporeninemic hypoaldosteronism is
and type 4. to mutations in the gene encoding carbonic anhydrase II, a cyto- probably more common in this age group than previously thought.
plasmatic enzyme responsible for the generation of HCO 3 and H+ Gordon syndrome, also called pseudohypoaldosteronism type 2, is a
2 The evaluation of the child with RTA includes obtaining his- from H2O and CO2. The genetic defect in this enzyme, which operates hereditary, autosomal-dominant disorder caused by gain of function
tory regarding abnormal growth pattern, polyuria, recurrent vomit- in both the proximal and distal tubule, can lead to combined distal mutations in the genes encoding WNK1 or WNK4 kinases. The con-
ing, pathologic fractures, psychomental retardation, family history of and proximal RTA (previously known as RTA type 3). sequence of the mutation is increased NaCl reabsorption in the distal
genetic diseases, intrauterine fetal demise or fetal uropathy and drug convoluted tubule which results in hypervolemia, hypertension,
administration. Physical examination includes weight and height 5 RTA types 1 and 4 are characterized by a positive urinary hyporeninemic hypoaldosteronism, hyperkalemia and type 4 RTA.
measurement, signs of rickets (bowing, frontal bossing, etc.), dys- anion gap which is due to impaired tubular NH+4 production or Aldosterone resistance with elevated plasma levels of aldosterone, is
morphic features and signs of hepato-/splenomegaly. Laboratory secretion. observed in PHA 1. This hereditary disorder presents clinically with
evaluation includes serum levels of creatinine, BUN, electrolyte lev- renal sodium wasting, hyperkalemia and metabolic acidosis. There
els, calcium, inorganic phosphorus, bicarbonate as well as plasma 6 DRTA is characterized by an impaired distal H+ secretion and, are two forms of PHA 1: in the renal, autosomal-dominant form, the
aldosterone levels and PRA. Urine should be obtained for urinalysis, hence, a failure to lower urine pH in the presence of acidosis. Several aldosterone resistance is limited to the kidney and is due to muta-
pH, osmolarity, Ca2+ and electrolyte levels (Cl , Na+ and K+). In addi- different mechanisms are responsible for this type of RTA: tions in the gene encoding the mineralocorticoid receptor. In the
tion, renal US should be performed in every child with suspected Secretory defect a defect in the H+-ATPase pump of the inter- autosomal-recessive multiple-end-organ form, the aldosterone
RTA. calated cell in the CCD. This abnormality can be a primary-genetic resistance is present in many organs (kidney, colon, lung, sweat and
disorder, or secondary to autoimmune diseases (SLE, Sjogren salivary glands) and is due to mutations in one of the -, -, or -sub-
3 A primary means by which the renal tubule handles an acid syndrome). units of the epithelial Na+ channel. There is also a secondary form
load is by production of ammonia (NH3). When combined with H+ in Gradient defect an increase in membrane permeability causing of aldosterone resistance, called PHA type 3, frequently observed in
the distal tubular lumen, NH3 is converted to ammonium ion (NH4+) backleak of luminal H+ in CCD cells. This condition is observed for infants with obstructive uropathy and/or urinary tract infection.
which is lipid-insoluble and therefore cannot be reabsorbed. example in children treated with amphotericin B.
Because a direct measurement of urinary ammonium excretion is Voltage-dependent defect a reduction in CCD Na+ reabsorption
cumbersome, urinary anion gap [Na+ + K+ Cl] serves as an indirect which diminishes the luminal electronegativity, thus impairing the Selected reading
index of urinary ammonium excretion and hence of distal acidifica- ability to secrete H+. This type of DRTA is accompanied by hyperka-
tion ability. This index is based on the fact that any change in urinary lemia and is seen in markedly volume-depleted children and sec- Fry AC, Karet FE: Inherited renal acidosis. Physiology 2007;22:
ammonium excretion will be accompanied by a parallel change ondary to amiloride treatment. 202211.
in urinary chloride excretion in order to maintain electroneutrality. A cardinal feature of DRTA is nephrolithiasis/nephrocalcinosis Herrin TH: Renal tubular acidosis; in Avner ED, Harmon WE,
A negative urinary anion gap (Cl > Na+ + K+) signifies normal caused by calcium- phosphate complexes. The reason for this abnor- Niaudet P (eds): Pediatric Nephrology, ed 5. Philadelphia,
ammonium production/secretion whereas a positive urinary anion mality is the combination of the acidic urine and hypocitraturia pro- Lippincott Williams & Wilkins, 2004, pp 757776.
gap (Cl < Na+ + K+) represents decreased ammonium production/ moting Ca-phosphorus precipitation. Mutations in the gene encod- Nicoletta JA, Schwartz GJ: Distal renal tubular acidosis. Curr Opin
secretion. ing the anion exchanger AE1 located in the -intercalated cells in the Pediatr 2004;16:194198.
CCD lead to both autosomal-dominant and autosomal-recessive Rodrguez Soriano J: Renal tubular acidosis: the clinical entity.
4 HCMA accompanied by negative urinary anion gap repre- DRTA. In the milder, autosomal-dominant type, the disease can man- J Am Soc Nephrol 2002;13:21602170.
sents an intact distal acidification mechanism. Besides gastrointesti- ifest as mild metabolic acidosis in older children or even adults, Rose BD, Post TW: Clinical Physiology of Acid-Base and Electrolyte
nal bicarbonate loss due to diarrhea, PRTA, also known as RTA type whereas in the recessive type, which is seen mainly in the southeast Disorders, ed 5. New York, McGraw-Hill, 2001, pp 612627.
2, is the most common cause of HCMA with a negative urinary anion Asian population, the clinical picture includes DRTA with hemolytic Scheinman SJ, Guay-Woodford LM, Thakker RV, Warnock DG:
gap. In addition to negative urinary anion gap, PRTA is characterized anemia. Autosomal-recessive DRTA coupled with sensorineural Genetic disorders of renal electrolyte transport. N Engl J Med
by hypokalemia and urinary pH < 5.5 in the face of systemic acidosis. hearing loss is caused by a genetic defect in the B1 subunit of the 1999;340:11771187.
PRTA can be isolated or can be a part of generalized proximal tubu- H+-ATPase transporter. Zelikovic I: Molecular pathophysiology of tubular transport
lopathy (Fanconi syndrome) which leads to hypophospatemic rickets, disorders. Pediatr Nephrol 2001;16:919935.
hypouricemia, glycosuria and aminoaciduria. For details on Fanconi 7 The primary pathogenic mechanism of RTA type IV is
61 aldosterone deficiency or resistance. In this type of RTA, the ability
syndrome, see appropriate algorithm. Major causes of PRTA/Fanconi
syndrome include: hereditary disorders (cystinosis, galactosemia, to acidify the urine is intact but NH+4 excretion and thus net acid
tyrosinemia, hereditary fructose intolerance, mitochondrial cytopa- excretion is reduced. Hyperkalemia is a main feature of this type of
thies and Wilson disease), drugs (aminoglycosides, ifosfamide, out- RTA. Low plasma aldosterone levels with elevated PRA is generally
/
Proximal tubulopathy (Fanconi syndrome)
62
Therapeutic strategies 4
Fluids, NaCl, KCl, NaHCO3 , PO4 , calcitrol, carnitine, specific therapy,
/
Polyuria
64
Hypouricemia
66 Serum uric acid <2 mg/dl
Medications 0 Medications 3
Ex. allopurinol Idiopathic renal hypouricemia 4
Metabolic disorders 1 Generalized proximal tubular defect 5
Xanthinuria 2 SIADH, extracellular volume expansion 6
/
Hyperuricemia
68
Elevated serum uric acid level (table 1)
Normal ECF volume Increased ECF volume Decreased ECF volume Increased uric acid excretion* Decreased uric acid excretion*
Cell lysis Acute renal failure 4 Diarrhea 5 Genetic diseases 2 Uromodulim disorders 3
Hemolysis Congestive heart failure Nephrogenic diabetes insipidus HGPRT deficiency FJHN
Polycythemia (Lesch-Nyhan syndrome) MCKD2
Leukemia/lymphoma PRPS overactivity GCKD
Tumor lysis syndrome G6P deficiency
Exercise, acidosis/alkalosis 0 (glycogen storage disease type 1)
Hypertension 1
Hereditary/metabolic conditions 23
Miscellaneous conditions
Hypothyroidism
Hypoparathyroidism
Psoriasis
Sarcoidosis
Obesity
Starvation
Down syndrome
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1 There are numerous medications that alter disease type 1) is an autosomal-recessive enzymatic
Selected reading
the metabolism of uric acid. Diuretics are the class of defect. Patients usually display hyperuricemia during
drugs most commonly associated with hyperuricemia infancy and gout later in life. In this disease there is Baldree LA, Stapleton FB: Uric acid metabolism in
(table 2). They initially cause a uricosuric response increased uric acid production due to depletion of children. Pediatr Clin N Am 1990;37:391418.
which is followed by decreased renal urate excretion. intracellular high energy phosphates and diffusion of Cameron JS, Moro F, Simmonds HA: Gout, uric acid
The antiuricosuric response is due to the extracellular adenosine out of the cell. and purine metabolism in paediatric nephrology.
fluid volume depletion induced by the diuretics and Pediatr Nephrol 1993;7:105118.
can be abolished by replacing urinary sodium losses. 5 FJHN, autosomal-dominant medullary cystic Cameron JS, Simmonds HA: Hereditary hyperurice-
kidney disease type 2 (MCKD2) and autosomal-domi- mia and renal disease. Semin Nephrol 2005;25:918.
2 The lactic acidemia induced by exercise nant GCKD constitute a group of hereditary renal dis- Scolari F, Caridi G, Rampoldi L, et al: Uromodulin
reduces uric acid excretion. Respiratory acidosis and eases that share an autosomal dominant pattern of storage diseases: clinical aspects and mechanisms.
diabetic ketoacidosis have been associated with transmission as well as hyperuricemia/gout and pro- Am J Kidney Dis 2004;44:987999.
reduced uric acid excretion. Metabolic alkalosis (espe- gressive renal damage that may cause end-stage renal Stapleton FB, Linshaw MA, Hassansein K: Uric acid
cially if associated with extracellular volume contrac- disease. Histologically, FJHN and MCKD2 are charac- excretion in normal children. J Pediatr 1978;92:911.
tion) can promote uric acid retention. terized by chronic interstitial nephritis with thickening
of the tubular basement membrane and corticomedul-
3 Hyperuricemia is a common finding in lary cysts, while GCKD is characterized by diffuse glo-
untreated hypertensive patients. It has been shown merular cysts caused by marked dilatation of Bowman
that uric acid affects vascular smooth muscle cells space in most glomeruli. These three diseases are
and endothelial cell proliferation and hyperuricemia caused by mutations in the gene encoding uromodu-
has been implicated in the pathogenesis of hyper- lim (Tamm-Horsfall protein), a protein which is exclu-
tension and vascular disease. sively expressed in the thick ascending limb of the
loop of Henle and the distal convoluted tubule. Lack of
4 These are examples of genetic diseases uromodulim function is associated with impairment of
which are associated with hyperuricemia. HGPRT defi- the urine-concentrating process, resulting in water
ciency (Lesch-Nyan syndrome) is an X-linked reces- depletion and hyperuricemia.
sive disorder in males. It is characterized by clinical
gout, hyperuricemia, nephrolithiasis, and a neurologic 6 In acute renal failure, there is a decrease in
syndrome of cerebral palsy, mental retardation, and the filtered load of uric acid presented to the renal Table 2. Selected medications associated with hyperuricemia
obsessive destructive and self-mutilating behavior. tubules. In addition, there may be increased uric acid
The disease can be diagnosed by demonstrating low synthesis secondary to catabolism. Increase uric acid production
Vitamin B12 (acute administration)
HGPRT level in erythrocytes of affected patients. PRPS Cytotoxic drugs
overactivity disorder is a heterogeneous X-linked 7 Diarrhea-induced volume contraction Ethanol
disorder associated with hyperuricemia, gout and diminishes urinary uric acid excretion and leads to 2-Ethylamoni-1,3,4-thiadiazole
nephrolithiasis frequently presenting in children less hyperuricemia. Fructose
than 10 years of age. G6P deficiency (glycogen storage Nicotinic acid
Pancreatic extract
/
Rickets
70 Serum total [Ca] 0
1,25(OH)2D 2
Vitamin D depletion 3 Chronic kidney disease 6 Pseudorickets : X-linked hypophosphatemic Disease not Vitamin D depletion 3 Lowered Elevated
Malabsorption 4 Early vitamin D treatment 7 rickets ; identified yet 8 Malabsorption 4
Liver diseases 5 Disease not identified yet 8 Autosomal dominant Liver diseases 5
hypophosphatemic rickets <
Tumor-induced osteomalacia = Chronic kidney Vitamin D-resistant
Hypophosphatemic rickets with disease 6 rickets B
hypercalciuria > 1A-Hydroxylase Dietary Ca deficiency
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1 Rickets is the clinical expression of undermineralization of 8 CKD refers to declining glomerular filtration rates, and is tions in the gene encoding NaPi IIc, a Na-P cotransporter of the proxi-
osteoid, produced at the epiphysis of growing bones, leading to disor- staged from 1 to 5. The inability to produce 1,25(OH)2D may appear in mal tubule. Any patient with hereditary hypophosphatemic rickets
dered endochondral bone formation. It represents not a single disease, CKD advanced stages (4 and 5) from the absence of sufficient kidney should be referred to an experienced center or practitioner in the nu-
but a process with wide heterogeneity. Clinical expression may occur mass, or related to hyperphosphatemia. In earlier CKD stages (2, 3) ances of its care.
in the skull, chest, pelvis, upper and lower extremities, with palpable, children may suffer metabolic acidosis that suppresses 1,25(OH)2D pro-
17 Children with idiopathic, or syndromic Fanconi syndrome
knobby-like enlargements. Skeletal deformity may result in a knock- duction also.
kneed or bowed appearance of the lower extremities. Dental develop- (see specific Algorithm chapter) commonly present with rickets. Fac-
ment may be impaired in primary and secondary dentition as well. Ra- 9 During vitamin D repletion, there are dys-synchronous tem- tors for its presence include chronic metabolic acidosis, hypophospha-
diographically, the most characteristic changes are in the epiphyses, poral changes with elevation of PTH remaining for several weeks to temia with insufficient production of 1,25(OH)2D, and/or CKD (see foot-
with widening, and an irregular, frayed, and cupped appearance. The months after restoration of circulating levels of 25(OH)D. note 14).
cortices are thin, and the bone appears with reduced density.
10 Disease not identified yet (DNIY). The clinician should be criti- 18 These diseases may resemble rickets. For details see algo-
2 Serum total calcium [Ca] is an easy differential point to begin cal in these circumstances. While new diseases, or explanations for rithm on Hypercalemia.
the evaluation of rickets. Normal ranges have been established for age. existing diseases, arise continually, it is often misleading information,
19 Autosomal-recessive, inherited absence of the proximal tu-
Its value may be lowered with concomitant hypoalbuminemia, or or misguided assays, that result in the disease not indentified yet clas-
raised with concomitant hyperproteinemia. Thus blood ionized calcium sification. bule 25-hydroxyvitamin D-1-hydroxylase has been referred to previ-
indicates if there is a real calcium disturbance. ously as vitamin D-dependent rickets, type 1. Currently this disease
11 Serum phosphorus (P) varies with age, time of day, and state entity should be referred as 1-hydroxylase deficiency. It responds to
3 Serum PTH refers to an immunometric assay measurement of acid-base balance. Normative values have been established. Re- physiologic replacement doses of the active hormone, 1,25(OH)2D.
to detect 1-84 PTH. While controversy exists as to the meaning of first duced P interpretation needs concomitant evaluation of P kidney han-
20 End-organ resistance to 1,25(OH)2D may occur in presence of
generation assays that may detect other N-terminal fragments, and dling (see algorithm for Hypophosphatemia).
thereby elevate the total PTH level, it is not clear that the newer assays mutated intracellular vitamin D receptor (VDR) resulting in a hypofunc-
offer better discrimination for rachitic diseases. PTH value must be in- 12 Pseudorickets refers to other metabolic, genetic, or structural tional or absent receptor. The disease has been called vitamin D-de-
terpreted with respect to either serum total Ca or ionized Ca. diseases in which the radiographic appearance more commonly than pendent rickets, type 2 in the past. The highest blood levels of
the clinical appearance resembles rickets. They include intrinsic bone 1,25(OH)2D in humans are seen here, with values often above 400 pg/ml
4 Measurement of circulating vitamin D metabolites is useful in disorders (chondrodysplasias), mucopolysaccharidoses, sex steroid (normal, 1580). Any patient with this disorder should be referred to an
the differential diagnosis. 25(OH)D is produced in the liver, and repre- hormonal insufficiency disorders, vitamin C deficiency, osteogenesis experienced center or practitioner in the nuances of its care.
sents the major substrate of the vitamin D. Its level defines sufficiency imperfecta, hypophosphatasia, osteopetrosis, craniometaphyseal dys-
21 Primary dietary calcium deficiency may produce a picture of
of the vitamin. Despite some ethnic differences 25(OH)D levels <5 ng/ plasia, and others.
ml are considered deficient. Values between 5 and 15 ng/ml should be rickets in the presence of adequate vitamin D. This picture has been
interpreted carefully with respect to the presence or absence of rickets. 13 X-linked hypophosphatemic rickets (XLH) is an X-linked, described in preterm neonates, and young infants and older children in
Circulating levels of 1,25(OH)2D, produced in the kidney proximal tu- dominant disease caused by Phex gene (Phosphate regulating with rural South Africa.
bule, but with some minor extrarenal production too, are often prob- Homologies to Endopeptidases on the X chromosome) mutations. The
lematic to interpret, except in the few circumstances noted in this algo- condition is associated with inappropriate phosphaturia. Levels of
rithm. The normal range is 2080 pg/ml. 1,25(OH)2D, that should be stimulated by hypophosphatemia, are often Selected reading
in the normal range, suggesting a second defect in the vitamin D
5 Vitamin D depletion is a common cause of rickets. Depletion
Cho HY, Lee BH, Kang JH, Ha IS, Cheong HI, Choi Y: A clinical and
system too. Phenotype-genotype relationships await clarification.
molecular genetic study of hypophosphatemic rickets in children.
is caused by a dietary lack of the parent compound, and/or insufficient
Pediatr Res 2005;58:329333.
sunlight exposure to have dermal conversion of precursors into vita- 14 XLH expression is mimicked by autosomal-dominant hypo-
Hochberg Z: Vitamin-D-dependent rickets type 2. Horm Res 2002;
min D. After restoration of body vitamin D stores the rachitic bone phosphatemic rickets, produced by mutations in the gene encoding
58:297302.
heals completely with no long-term consequences generally. FGF-23, a potent phosphaturic agent.
Holick MF: Resurrection of vitamin D deficiency and rickets.
6 Malabsorption may produce functional vitamin D deficiency 15 Some primitive, ectodermally derived tumors may produce a
J Clin Invest. 2006;116:20622072.
Klein GL, Soriano H, Shulman RJ, Levy M, Jones G, Langman CB:
due to its solubility. Processes that impair fat absorption (sprue, inflam- substance leading to inappropriate phosphaturia, hypophosphatemia,
Hepatic osteodystrophy in chronic cholestasis: evidence for a
matory bowel diseases, cystic fibrosis, etc.) will lead to lowered vita- and rickets (in children) or osteomalacia (in adults). Hence, tumor-in-
multifactorial etiology. Pediatr Transplant 2002;6:136140.
min D body stores and reduced conversion to the 25(OH)D substrate. duced osteomalacia denomination has been applied to both conditions.
Langman CB: Disorders of phosphorus, calcium and vitamin D;
Removal of the tumor results in complete correction of the rachitic
71 7 25(OH)D is produced in hepatocytes by a cytosolic mixed in Avner ED, Harmon WE, Niaudet P (eds): Pediatric Nephrology, ed 5.
state, although the presence of the tumor may be difficult to demon-
Philadelphia, Lippincott Williams & Wilkins, 2004, pp 237254.
function P450 enzyme, whose gene has been cloned and sequenced. Al- strate.
Thacher TD, Fischer PR, Pettifor JM: Rickets: vitamin D and calcium
terations in hepatic production leading to substrate deficiency include
deficiency. J Bone Miner Res 2007;22:638.
hepatic mass reduction, alterations in P450 enzyme activity, xenobiotics 16 Two inheritance patterns, autosomal dominant or recessive,
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Tubular disease G. Ariceta B. Hoppe C.B. Langman Rickets
Fluid/electrolyte/acid base balance S. Watkins D. Okamura J. Rodrguez Soriano Hyponatremia
/
Hyponatremia
(Serum Na+ <130 mEq/l)
72
Exclude pseudohyponatremia or hypertonic hyponatremia /
Variable 8
[Na+] >20 [Na+] <20 [Na+] <20 29 [Na+] >20
Sodium and water replacement ; Water restriction ; Sodium and water restriction ;
4 Renal etiology: Kidney disease can cause both fluid reten- 11 The hyponatremia in hypervolemic/edematous states is
tion and excess sodium losses. characterized by high total body sodium content due to avid renal
sodium retention. In these conditions, the hyponatremia is primarily Table. Causes of SIADH
5 Salt-losing nephropathies include any form of renal disease due to water retention. In the setting of liver failure and nephrotic I. Increased hypothalmic production of ADH
that cause an impairment in sodium reabsorbtion and hence free wa- syndrome, intravascular volume depletion and hypoalbuminemia
Neuropsychiatric disorders
ter excretion. Etiologies include: Bartters syndrome and Gitelmans contribute to urinary sodium retention leading to hypervolemia. 1. Infections: meningitis (tuberculous or bacterial), encephalitis, abscess,
syndrome, renal tubular acidosis, TIN, pyelonephritis and hypo- or herpes zoster 2. Vascular: thrombosis, subarachnoid or subdural hemorrhage,
pseudohypoaldosteronism. Hypoaldosteronism (aldosterone defi- 12 In renal failure, the combination of water retention and de- cavernous sinus thrombosis, cerebrovascular accident 3. Neoplasm:
ciency) will result in high urine sodium and water losses and its main creased tubular ability to reabsorb sodium causes hyponatremia and primary or metastatic 4. Skull fracture, head injury 5. Psychosis, delirium
causes are immune-mediated diseases (polyglandular or isolated), elevated urinary sodium concentration. tremens 6. Other: Guillain-Barr syndrome, acute intermittent porphyria,
autonomic neuropathy, hypothalamic sarcoidosis, postpituitary surgery,
salt-losing forms of CAH and adrenoleukodystrophy. Pseudohypo- multiple sclerosis, epilepsy, hydrocephalus, lupus erythematosus, peripheral
aldosteronism is caused by primary or acquired diseases character- 13 Management of hyponatremia: In the stable patient, serum neuropathy, spinal cord lesions
ized by end organ resistance to aldosterone. Laboratory investiga- sodium levels should be normalized slowly to prevent central pon-
Drugs
tion of salt-losing nephropathies includes: Serum and urine osmolar- tine myelinolysis. The amount of sodium to be replaced in hypovole- 1. Intravenous cyclophosphamide (increased sensitivity may also
ity, serum BUN, creatinine, electrolytes, acid-base status, plasma mic hyponatremia can be assessed by the formula: contribute) 2. Carbamazepine (though increased sensitivity is probably
aldosterone levels, urinary electrolyte levels and renal sonogram. important) 3. Vincristine or vinblastine 4. Psychiatric drugs
Na+ deficit = (serum Na+ concentration desired 5. Bromocriptine 6. Clofibrate 7. General anesthesia 8. Narcotics, opiate
serum Na+ concentration present) TBW, derivatives
6 In metabolic alkalosis (as well as in some forms of RTA)
the hyponatremia is due to urinary losses of Na+ that accompany the where TBW (total body water) = 0.6 body weight (kg). Correction of Pulmonary disease
bicarbonaturia. serum Na+ levels should be done cautiously and should not exceed 1. Pneumonia: viral, bacterial, fungal 2. Tuberculosis 3. Lung abscess,
empyema 4. Acute respiratory failure 5. Positive pressure ventilation
10 mEq/l/day. Diuretics hypertonic saline should be only considered 6. Other: asthma, COPD, atelactasis, pneumothorax, cystic fibrosis
7 The features of cerebral salt wasting are similar to those of in the patient with neurologic changes (seizure, coma), and should
Miscellaneous
SIADH except for volume depletion which is a feature of the former. only be done in the pediatric intensive care unit setting. Of note, loop
Postoperative patient, severe nausea, pain, infection with HIV, idiopathic
Cerebral salt wasting is characterized by excessive urinary sodium diuretics, but not thiazides, should be used since the former augment
losses in patients with intracranial disease. The exact mechanism is excretion of electrolyte free water. In the setting of cortisol deficiency II. Ectopic (nonhypothalamic) production of ADH
73 or hypothyroidism, treatment with thyroid replacement or glucocor-
1. Ewing sarcoma 2. Hodgkin disease, leukemia 3. Pulmonary tuberculosis
unknown but it has been speculated that the Na+ loss is due to the
release of a natriuretic factor, probably from the injured brain. ticoid therapy is indicated. If true hypoaldosteronism or cerebral salt III. Potentiation of ADH effect
1. Chlorpropamide 2. Carbamazepine 3. Psychosis 4. Intravenous
wasting is diagnosed, treatment with mineralocorticoids is indicated.
cyclophosphamide 5. Prostaglandin synthesis inhibitors (salicylates,
8 Gastrointestinal Na+ losses: Gastrointestinal disease can NSAIDS)
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Fluid/electrolyte/acid base balance S. Watkins D. Okamura J. Rodrguez Soriano Hyponatremia
Fluid/electrolyte/acid base balance S. Watkins D. Okamura J. Rodrguez Soriano Hypernatremia
/
Hypernatremia
(Serum Na+ >150 mEq/l)
74
>800 <300
Yes No
CDI 5 NDI 6
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1 Serum sodium will be elevated in the setting of sodium ex- 8 NDI is a congenital or acquired disorder in which hypotha-
Selected reading
cess or water losses. A thorough clinical evaluation of the child to lamic function and ADH production and secretion are normal but
determine his volume status is therefore vital in order to proceed there is a lack of renal responsiveness to ADH. Congenital NDI is in- Avner ED: Clinical disorders of water metabolism: hyponatremia
with the work-up: (1) History: Information from patient/family on herited in an X-linked, autosomal-recessive or, rarely, autosomal- and hypernatremia. Pediatr Ann 1995;24:2330.
weight changes, intake and output (urinary, gastric, stool), medica- dominant fashion. The X-linked disease is due to different mutations Moritz ML, Ayus JC: Preventing neurological complications from
tion history. (2) Examination: Weight, skin changes (edema, turgor), in the ADH (V2) receptor gene. The autosomal-recessive and autoso- dysnatremias in children. Pediatr Nephrol 2005;20:16871700.
fontanelle changes, blood pressure/orthostatics, mucous mem- mal-dominant forms are caused by mutations in the H2O channel Rose BD, Post TW: Clinical Physiology of Acid-Base and Electrolyte
branes, cardiac gallop. Due to the fact that in hypernatremic dehydra- (AQP2) gene. Major causes of acquired NDI include lithium adminis- Disorders, ed 5. New York, McGraw-Hill, 2001, pp 750758.
tion the ECF volume may be preserved, the classic signs of dehydra- tration, hypercalcemia, hypokalemia and osmotic diuresis associated Trachtman H: Sodium and water; in Avner ED, Harmon WE,
tion (sunken eyes and fontanelle, reduced skin turgor, hypotension) with uncontrolled diabetes mellitus. Niaudet P (eds): Pediatric Nephrology, ed 5. Philadelphia,
may be absent. Lippincott Williams & Wilkins, 2004 pp 125145.
9 Sodium excess can be due to exogenous administration of
2 Once fluid status is assessed, patients work-up can be ap- sodium (improperly mixed formulas or NaCl or NaHCO3 administra-
propriately directed. Determination of urine Na+ concentration is es- tion). Infants are especially susceptible to sodium overload. For ex-
sential for narrowing the differential diagnosis. It should be empha- ample, the administration of only 1 tablespoon of NaCl to a newborn
sized that there is no correlation between urinary Na+ level (which is infant can raise the plasma Na by as much as 70 mEq/l. Sodium ex-
normally determined by the ECF volume status), and serum Na+ con- cess can also be secondary to mineralocorticoid excess. In this con-
centration. dition, the hypernatremia is usually mild or even absent, and the
main electrolyte abnormalities are hypokalemia and hypochloremia
3 In renal conditions causing hypernatremia, there are usually (see, Hypokalemia and Hypochloremia).
both water and sodium losses, but the water losses exceed the so- Table. Causes of SIADH
dium losses. The water loss is usually secondary to the reduced uri- 10 Rapid correction of hypernatremia can induce cerebral ede- I. Increased hypothalmic production of ADH
nary concentrating ability present in these patients. ma, seizures, permanent neurologic damage and death. These com-
Neuropsychiatric disorders
plications are a result of rapid reduction in ECF osmolality causing
1. Infections: meningitis (tuberculous or bacterial), encephalitis, abscess,
4 Diarrhea is the most common cause of hypernatremic de- entry of water into cells in the brain and cerebral edema. To minimize herpes zoster 2. Vascular: thrombosis, subarachnoid or subdural hemorrhage,
hydration in children, especially in infants. Other causes of extrarenal this risk, the plasma sodium level should be slowly reduced unless cavernous sinus thrombosis, cerebrovascular accident 3. Neoplasm:
hypernatremic dehydration in children such as losses from skin are the patient has symptomatic hypernatremia. The rate at which the primary or metastatic 4. Skull fracture, head injury 5. Psychosis, delirium
much less common in children. sodium concentration should be lowered is no more than 0.5 mEq/l tremens 6. Other: Guillain-Barr syndrome, acute intermittent porphyria,
autonomic neuropathy, hypothalamic sarcoidosis, postpituitary surgery,
per hour or 12 mEq/l per day. Since most cases of hypernatremia are
multiple sclerosis, epilepsy, hydrocephalus, lupus erythematosus, peripheral
5 The normal response to the elevated plasma osmolarity is due to water loss, gradual correction requires calculation of free wa- neuropathy, spinal cord lesions
secretion of ADH resulting in renal water reabsorption and hence ter deficit [Water deficit = 0.6 weight (kg) (plasma Na/140 1)]. Fre-
Drugs
elevated urine osmolality, usually above 800 mosm/kg. Thus, in the quent monitoring of electrolyte levels is necessary to assure gradual 1. Intravenous cyclophosphamide (increased sensitivity may also
hypernatremic patient, the urine osmolality determines whether reduction of hypernatremia. In CDI, treatment involves careful use of contribute) 2. Carbamazepine (though increased sensitivity is probably
there is a urinary concentrating defect. DDAVP at minimum dose needed to maintain an adequate urine out- important) 3. Vincristine or vinblastine 4. Psychiatric drugs
put. Treatment of NDI may involve use of a thiazide diuretic (which 5. Bromocriptine 6. Clofibrate 7. General anesthesia 8. Narcotics, opiate
6 Water deprivation test should be done in a hospital setting decreases ECF volume thereby increasing H2O reabsorption) and po- derivatives
with close observation of vital signs and urine output. Monitor tassium-sparing diuretic such as amiloride. Pulmonary disease
weight, blood pressure, heart rate, electrolytes, serum and urinary 1. Pneumonia: viral, bacterial, fungal 2. Tuberculosis 3. Lung abscess,
empyema 4. Acute respiratory failure 5. Positive pressure ventilation
osmolality every hour for 4 h. Give DDAVP intranasally if patient is 6. Other: asthma, COPD, atelactasis, pneumothorax, cystic fibrosis
polyuric or urine osm/serum osm <1.5. After 1 h, if patient is still
Miscellaneous
polyuric or urine osm/serum osm <1.5, replace urine output ml for ml
Postoperative patient, severe nausea, pain, infection with HIV, idiopathic
for 2 h then recheck weight and electrolyte levels. Test is completed
after 7 h. If the patient responded to ADH with increased urine osmo- II. Ectopic (nonhypothalamic) production of ADH
1. Ewing sarcoma 2. Hodgkin disease, leukemia 3. Pulmonary tuberculosis
lality, decreased urine output and decreased serum osmolality, liber-
alize fluids cautiously. Watch input closely to avoid water intoxica- III. Potentiation of ADH effect
1. Chlorpropamide 2. Carbamazepine 3. Psychosis 4. Intravenous
tion. If patient did not respond to ADH, then patient has NDI and lib-
75 cyclophosphamide 5. Prostaglandin synthesis inhibitors (salicylates,
eralize fluids ad libitum. NSAIDS)
IV. Exogenous administration of ADH
7 CDI is caused by impaired production or secretion of ADH. Vasopressin, desmopressin, oxytocin
Common causes of CDI include craniopharyngioma, trauma, malig-
/
Hypochloremia
(Serum Cl <100 mEq/l)
76
Urine Cl 1 Hypertension
Urine Cl >10 mEq/l
PRAm6
Yes 2 No
Dietary chloride deficiency Vomiting Cystic fibrosis Bartter syndrome Liddle syndrome Glucocorticoid-remediable aldosteronism
in neonates (maternal vomiting) Pyloric stenosis, psychogenic Excessive sweating Gitelman syndrome AME Primary hyperaldosteronism
Prebiliary obstruction Burns Diuretics Licorice ingestion
Intracranial hypertension Gluco- or mineralocorticoid
Gastric drainage administration
/
Hyperchloremia
(Serum Cl >110 mEq/l)
78
No Yes
Negative 2 Positive 3
79
/
Hypokalemia
(Plasma K+ <3.5 mEq/l)
80
Urine K+
PRA
Parenteral fluids
Protein-calorie malnutrition
Low 5 High 8
Associated with alkalosis Cystic fibrosis Metabolic alkalosis Postobstructive diuresis Low/normal 6 High 7
Vomiting, gastric drainage Excessive sweating Insulin administration Recovery from ARF
Congenital chloride diarrhea Burns B2-Agonists administration RTA type 1
Associated with acidosis Barium poisoning Fanconi syndrome
Profuse or prolonged diarrhea Familial hypokalemic Bartter syndrome Liddle syndrome Glucocorticoid-remediable
Malabsorption, biliary/intestinal fistula periodic paralysis Gitelman syndrome AME aldosteronism
Enterostomy losses, ureterosigmoidostomy Diuretics Licorice ingestion Primary hyperaldosteronism
Unpredictable acid-base abnormality Gluco- or mineralocorticoid
/
Hyperkalemia
(Plasma K+ >5.2 mEq/l)
82
Exclude spurious hyperkalemia or pseudohyperkalemia 0
Urine K+
PRA
High 6 Low 7
Acute hemolysis Metabolic acidosis Acute renal failure Defective renal secretion CAH Hyporeninemic hypoaldosteronism PHA type 1 and 3
GI bleeding Insulin deficiency Chronic renal failure Sickle cell disease, SLE, Salt-losing CAH Gordon syndrome (PHA type 2)
Rhabdomyolysis, exercise Drugs obstructive uropathy Adrenocortical failure
Infection B 2-Blockers therapy RTA type 1 (hyperkalemic form) CMO deficiency type 1 and 2
Burns Digoxin overdose Drugs
Surgery Succinylcholine Spironolactone, triamterene, amiloride,
Prematurity ACE inhibitors, heparin, cyclosporine A,
Hyperosmolality NSAID, trimethoprim
Diet Familial hyperkalemic
Oral or i.v. K+ load periodic paralysis
Transfusions
/
Metabolic acidosis
84 Renal failure 0
No Yes
Normal (1012 mEq/l) Blood anion gap 1 Increased < Blood lactate
Cl >Na++K+ 3 Cl <Na++K+ 4
Blood glucose
Urine ketones
>5.8 <5.8
Elevated Negative
Serum K+
RTA type 4 7
Hypoglycemic Toxicology
syndromes
Low High PRA Fasting Negative
Positive
High Low
Distal RTA Hyperkalemic
(type 1) 5 distal RTA (type 1) 6
Blood pressure
Plasma aldosterone
Diabetes mellitus Acute failure Chronic failure
High Normal Nondiabetic causes
Low High
Plasma cortisol
Renal US
Normal Low
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Acetazolamide administration (PHA type 2) Solid tumors Methanol Urine for reducing substances,
Exogenous acid administration Salicylates organic and amino acids
TPN Muscle hyperactivity
Ureterosigmoidostomy Tissue hypoperfusion
and hypoxia
Addison disease PHA type 3 Inherited and
Congenital adrenal (vesicoureteral reflux, obstructive uropathy, metabolic disorders
hyperplasia pyelonephritis) 9 Diabetes mellitus
1 MA is characterized by low blood HCO3 level as well as by drase, an enzyme which has a major role in tubular bicarbonate re- 12 Gordons syndrome, also called pseudohypoaldostreonism
low pCO2 level caused by compensatory hyperventilation. generation. Inhibition of this enzyme will cause HCMA. Other causes type 2, is a hereditary, autosomal-dominant disorder caused by gain
of HCMA with a negative urinary anion gap are rare in children. of function mutation in the genes encoding WNK1 or WNK4 kinases.
2 MA in renal failure is usually associated with increased se- The consequence of the mutation is increased NaCl reabsorption in
rum anion gap [Na+ HCO3 CI ] due to accumulation of acids in the 6 RTA types 1 and 4 are characterized by a positive urinary the distal convoluted tubule which results in hypervolemia, hyper-
blood. However, due to tubular damage, a component of normal an- anion gap [Cl < Na+ + K+] which is due to impaired tubular NH4+ pro- tension, hyporeninemic hypoaldosteronism, hyperkalemia and type
ion gap acidosis is often added, resulting in a mixed picture. duction or secretion. 4 RTA.
3 Calculation of the serum anion gap [Na+ HCO3 Cl ] is es- 7 RTA type 1 (distal RTA) is characterized by an impaired distal 13 Hyporeninemic hypoaldosteronism can be caused by vari-
sential for the evaluation of MA. In normal anion gap MA, hyperchlo- H+ secretion and, hence, a failure to lower urine pH in the presence of ous conditions including:
remia compensates for the loss of bicarbonate. In contrast, in high acidosis. Several different mechanisms are responsible for this type interstitial nephritis, sickle cell nephropathy, amiloride administra-
anion gap MA (characterized by the presence of anions other than of RTA: tion, diabetes mellitus, obstructive uropathy and others. Although
bicarbonate), the serum chloride level remains within normal limits. Secretory defect a defect in the H+-ATPase pump of the interca- considered rare in children, hyporeninemic hypoaldosteronism is
lated cell in the CCD. This abnormality can be a primary-genetic dis- probably more common in this age group than previously thought.
4 A primary means by which the renal tubule handles an acid order, or secondary to autoimmune diseases (SLE, Sjogren syn-
load is by production of ammonia (NH3). When combined with H+ in drome). 14 Increased serum anion gap indicates that an unmeasured
the distal tubular lumen, NH3 is converted to ammonium ion (NH4+) Gradient defect an increase in membrane permeability causing anion is added to the blood, either endogenously (lactate, ketone
which is lipid-insoluble and therefore cannot be reabsorbed. Be- backleak of luminal H+ in CCD cells. This condition is observed for bodies, organic acids) or exogenously (salicylates, ethelene glycol,
cause a direct measurement of urinary ammonium excretion is cum- example in children treated with amphotericin B. methanol). For details on the various disorders leading to high anion
bersome, urinary anion gap [Na+ + K+ Cl] serves as an indirect in- gap MA in children see appropriate references.
dex of urinary ammonium excretion and hence of distal acidification 8 Hyperkalemic distal (type 1) RTA is seen mainly in associa-
ability. Any change in urinary ammonium excretion will be accompa- tion with obstructive uropathy in markedly volume-depleted children
nied by a parallel change in urinary chloride excretion in order to and secondary to amiloride treatment. In this type of distal RTA (also Selected reading
maintain electroneutrality. Anions like ketone bodies and certain an- known as voltage-type distal RTA), there is a reduction in Na+ reab-
tibiotics may interfere with calculation of the urine anion gap. Fur- sorption in the cortical collecting duct, which diminishes the tubular Batlle D, Moorthi KM, Schlueter W, Kurtzman N: Distal renal tubular
thermore, NH4+ excretion decreases in the face of hypovolemia and lumen electronegativity, thus impairing distal H+ and K+ secretion. acidosis and the potassium enigma. Semin Nephrol 2006;26:
avid tubular Na reabsorption (urine Na <20 mEq/l). 471478.
9 RTA type 4 is characterized by hyperkalemia and decreased Hanna JD, Scheinman JI, Chan JCM: The kidney in acid-base
5 HCMA accompanied by negative urinary anion gap [Cl > ability to secrete NH4+. balance. Pediatr Clin N Am 1995;42:1365.
Na+ + K+] represents an intact distal acidification mechanism. Gastro- Herrin TH: Renal tubular acidosis; in Avner ED, Harmon WE,
intestinal bicarbonate loss due to diarrhea is the most common 10 11 PHA types 1 and 3 are characterized by hyponatremia, Niaudet P (eds): Pediatric Nephrology, ed 5. Philadelphia,
cause of HCMA in children. Proximal RTA (RTA type 2) does not usu- hypernatriuria, hyperkalemia and metabolic acidosis. There are two Lippincott Williams & Wilkins, 2004, pp 757776.
ally interfere with urinary ammonium excretion. Proximal RTA can forms of PHA 1: in the renal, autosomal-dominant form, the aldoste- Krapf R, Seldin DW, Alpern RJ: Clinical syndromes of metabolic
be isolated or can be a part of generalized proximal tubulopathy rone resistance is limited to the kidney and is due to mutations in the acidosis; in Seldin DW, Giebisch G (eds): The Kidney:
(Fanconi syndrome) which leads to hypophosphatemic rickets, gene encoding the mineralocorticoid receptor. In the autosomal-re- Physiology and Pathophysiology, ed 3. Philadelphia, Lippincott
hypouricemia, glycosuria and aminoaciduria. Major causes of proxi- cessive, multiple-end-organ form, the aldosterone resistance is Williams & Wilkins, 2000, pp 20732130.
85 mal RTA/Fanconi syndrome include: hereditary disorders (cystinosis, present in many organs (kidney, colon, lung, sweat and salivary Nicoletta JA, Schwartz GJ: Distal renal tubular acidosis.
galactosemia, tyrosinemia, hereditary fructose intolerance, mito- glands) and is due to mutations in one of the -, - or -subunits of Curr Opin Pediatr 2004;16:194198.
chondrial cytopathies and Wilson disease), drugs (aminoglycosides, the epithelial Na+ channel. There is also a secondary form of aldoste- Rodrguez Soriano J: Renal tubular acidosis: the clinical entity.
ifosfamide, outdated tetracyclines), heavy metal poisoning, and ge- rone resistance called PHA type 3, frequently observed in infants J Am Soc Nephrol 2002;13:21602170.
/
Metabolic alkalosis
86 Urine chloride
No Low Cl intake
Normal High
No Loop, thiazides
Diarrhea Yes
High 3 Low 4
No Congenital CI diarrhea
Colonic adenoma
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1 Metabolic alkalosis is characterized by elevat- 5 Glucocorticoid-remediable aldosteronism is
Selected reading
ed serum HCO3 and pCO2 levels. The latter is caused an inherited, autosomal-dominant disease, which is a
by compensatory hypoventilation. Metabolic alkalosis result of formation of a chimeric gene that possesses Galla JH: Metabolic alkalosis. J Am Soc Nephrol
is usually associated with hypochloremia and it is of- the 5-11-hydroxylase and the 3-aldosterone syn- 2000;11:369375.
ten difficult to establish which of these two laboratory thase sequences. In this situation, aldosterone secre- Laski ME, Sabatini S: Metabolic alkalosis, bedside
findings is the primary phenomenon. Metabolic alkalo- tion is under the influence of ACTH instead of angio- and bench. Semin Nephrol 2006;26:404421.
sis can be accompanied by either hypovolemia or eu- tensin II and is completely suppressed by dexametha- Oh MS, Carroll HJ: Mechanism of chloride deficit in
volemia/volume excess. A thorough clinical evaluation sone administration. The diagnosis of primary hyper- the maintenance of metabolic alkalosis. Nephron
of the child to determine his volume status is therefore aldosteronism (Conn disease) is rarely made in chil- 2002;91:379382.
vital in order to proceed with the work-up: dren. Rodrguez Soriano J: Tubular disorders of electro-
I. History: Information from patient/family of weight lyte regulation; in Avner ED, Harmon WE, Niaudet P
changes, intake and output (urinary, gastric, stool), 6 Liddle syndrome is a rare hereditary autoso- (eds): Pediatric Nephrology, ed 5. Philadelphia,
medication history. mal-dominant disease characterized by low renin, vol- Lippincott Williams & Wilkins, 2004, pp 729756.
II. Examination: Weight, skin changes (edema, turgor), ume expansion and hypertension due to excessive Wesson DE, Alpern RJ, Seldin DW: Clinical
fontanelle changes, blood pressure/orthostatics, and unregulated NaCl reabsorption in the distal neph- syndromes of metabolic alkalosis; in Seldin DW,
mucous membranes, cardiac gallop. ron. This situation is due to gain of function mutation Giebisch G (eds): The Kidney: Physiology and
in the genes encoding the - or -subunits of the epi- Pathophysiology, ed 3. Philadelphia, Lippincott
2 Most conditions that lead to metabolic alkalo- thelial Na+ channel. AME is caused by inactivating mu- Williams & Wilkins, 2000, pp 20552072.
sis and are associated with high urine chloride level tations in the gene encoding renal 11-hydroxysteroid Zelikovic I: Molecular pathophysiology of tubular
and are regarded as chloride-resistant. dehydrogenase type 2. The defective enzyme does not transport disorders. Pediatr Nephrol 2001;16:
inactivate cortisol, which in turn binds to the mineralo- 919935.
3 As a rule of thumb, the earlier the age of pre- corticoid receptor to cause Na+ retention, hyperten-
sentation of hereditary potassium-losing nephropa- sion and hypokalemia. Ingestion of licorice which in-
thies, the more severe the presentation. When pre- hibits 11-hydroxysteroid dehydrogenase type 2, may
sented in early childhood, it is often associated with cause similar abnormalities.
severe urinary losses of Na and Cl and failure to thrive
(Bartter syndrome). In later childhood, presentation is 7 In the majority of these conditions urine chlo-
milder, at times with tetany due to hypomagnesemia/ ride level is expected to be low.
hypocalcemia (Gitelman syndrome). These syndromes
mimic the pictures seen when either loop diuretics or 8 The combination of metabolic alkalosis and
thiazides are used, with reduction in NaCl reabsorp- low urine Cl level is observed in conditions caused
tion in the loop of Henle (Bartter syndrome) or the dis- either by low chloride intake or extrarenal losses of
tal tubule (Gitelman syndrome), respectively. Bartter this ion, through the gastrointestinal tract or the skin.
syndrome is characterized by urinary calcium losses These disorders are characterized by volume depletion
whereas Gitelman syndrome by increased urinary and low urinary chloride concentration and are regard-
magnesium losses. ed as chloride responsive. For details on these condi-
tions, see sections on Hypokalemia and Hypochlore-
4 The combination of hyperkaliuric hypokale- mia.
mia, metabolic alkalosis, elevated blood pressure and
elevated plasma renin and aldosterone levels in chil-
dren is almost always due to renovascular disease.
Major etiologies include: renovascular changes sec-
ondary to umbilical artery catheter in newborn infants,
arteritis secondary to Takayasu or Moyamoya disease,
fibromuscular dysplasia (idiopathic or secondary to
neurofibromatosis type 1), or extrinsic compression of
87 the renal artery due to a tumor, hematoma or fibrosis.
Although the gold standard for the diagnosis of renal
artery stenosis is selective renal angiogram, currently
CT angiography is the preferred mode of imaging. Re-
/
Hypovolemia
88 Trauma, bleeding Normal/high 9
Environmentally induced hypovolemia
Serum Na
No
Response to ADH
Yes No
CNS Respiratory GI tract losses 3 Skin Third spacing
Pharmacotherapy Yes No
Toxicology
Serum albumin
Metabolic Metabolic Central Renal
alkalosis acidosis
Yes No
Ascites
Anasarca Acute Vascular Normal Low
abdomen 8 pathology
High Negative
Serum
1 Hypovolemia is characterized by rapid heart rate, decreased 8 Although massive proteinuria often results in hypovolemia, Selected reading
tissue perfusion and at times lowered blood pressure. A thorough some patients remain euvolemic. The volume status can be assessed
clinical evaluation of the hypovolemic child is vital in order to pro- by measuring FENa, which is very low in hypovolemic states, or in Bockenkamp B, Vyas H: Understanding and managing acute fluid
ceed with the work-up: conditions characterized by low effective circulatory volume (e.g. NS, and electrolyte disturbances. Curr Paediatr 2003;13:520528.
I. History: Information from patient/family on weight changes, intake congestive heart failure, etc.). Boluyt N, Bollen CW, Bos AP, Kok JH, Offringa M: Fluid resuscita-
and output (urinary, gastric, stool), medication history. tion in neonatal and pediatric hypovolemic shock: a Dutch
II. Examination: Weight, skin changes (edema, turgor), fontanelle 9 A large pleural effusion, especially when continuously Pediatric Society evidence-based clinical practice guideline.
changes, heart rate, blood pressure/orthostatics, mucous mem- drained, can result in hypovolemia. Intens Care Med 2006;32:9951003.
branes, cardiac gallop, capillary refill time. Finberg L: Dehydration in infancy and childhood. Pediatr Rev
10 Some of these conditions, if becoming long-standing, can 2002;23:277282.
2 Hypovolemia accompanied by low urine volume (below 1 result in hypoalbuminemia. Nicholls MG: Unilateral renal ischemia causing
ml/kg/h) usually indicates that the ability of the kidneys to conserve the hyponatremic hypertensive syndrome in children more
water is intact and that the cause of the hypovolemia is extrarenal. 11 The combination of hypovolemia with high urine output common than we think? Pediatr Nephrol 2006;21:887890.
indicates that there is an impairment in renal water reabsorption, Rose BD, Post TW: Clinical Physiology of
3 Patients with adipsia/hypodipsia often have additional CNS either due to an intrinsic renal defect or secondary to an osmotic Acid-Base and Electrolyte Disorders, ed 5.
manifestations. As some of them may also have partial ADH defi- substance in the urine that interferes with normal renal concentrat- New York, McGraw-Hill, 2001, pp 415446.
ciency, urine volume may vary. Typically, these patients are at risk to ing mechanisms. Trachtman H: Sodium and water homeostasis. Pediatr Clin N Am
develop hyperosmolar dehydration. 1995;42:1343.
12 Salt-losing nephropathies include any form of renal disease
4 Loss of water through the respiratory system may be in- that causes an impairment in sodium reabsorption and hence free
creased especially during mechanical ventilation. water excretion. For further details, see Hyponatremia.
5 GI tract losses may result in hypo-, iso- or hyperosmolar 13 The hyponatremic hypertensive syndrome is a rare disor-
dehydration. der seen mainly in infants and young children. It is caused by severe
primary or secondary hyperreninemia, severe hypertension and
6 In a patient with excessive sweating, one needs to rule out consequently pressure diuresis. Once the patient becomes severely
89
cystic fibrosis. dehydrated, urine volume declines. Losses of sodium and water stop
when the hypertension is corrected.
7 Insensible losses of water through the skin are more com-
mon in the newborn due to the higher skin surface area to body mass
/
Edema
90
Symmetrical Localized/unilateral
Hypoalbuminemia
Angioedema A Venous B Lymphatic C Infectious C
Yes No
Albuminuria TSHMT4m
No Yes No Yes
Serum creatinineM
No Yes
Hematuria
No Yes
No Yes
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Fluid/electrolyte/acid base balance W. Proesmans U.S. Alon Edema
Divalent ion metabolism G. Ariceta B. Hoppe C.B. Langman Hypocalcemia
/
Hypocalcemia Symptoms 0
92 mSerum PO4
MSerum alkaline phosphase
Yes No
Calcipenic rickets 1 No
Serum PTH
Serum 25(OH)D3
Elevated Low
Absent/low Normal
Serum creatinineM
PHP type 1 =
Gs A-protein reduced in
red blood cells
Yes No
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1 When serum albumin is normal, hypocalcemia is defined as 7 Hypocalcemia (usually associated with hyperphosphate- 14 To accurately define the types of PHP, urinary cAMP levels
a decrease in serum Ca concentration <2.1 mmol/l or 8.4 mg/dl, or as mia) may be due to transient or permanent hypoparathyroidism. following a PTH infusion test should be measured. In normal sub-
a decrease in ionized [Ca2+] <1.1 mmol/ or 4.4 mg/dl. If serum albumin Transient hypoparathyroidism is seen in neonates and is typically jects, cAMP levels obtained it this test will be elevated.
levels are low, serum total calcium might be low as well, but ionized categorized to early and late forms. The early form appears in the
Ca2+ values will still be in the normal range. Ionized Ca2+ levels are first few days of life, it usually presents with asymptomatic hypocal- 15 In PHP type 1, urinary cAMP elevation after PTH infusion is
dependent on the blood pH, with a decrease in [Ca2+] in alkalosis and cemia, and is seen most commonly in preterm and low-birth-weight reduced compared to normal. Three subtypes are further differenti-
an increase in acidosis (0.21 mmol/l change per 0.1 unit pH change). infants or in children of diabetic mothers. The late form is seen after ated. Types 1a and 1c appear phenotypically as McCune-Albright
the 1st week of life, it may present with seizures and tetany, and it is osteodystrophy with hypothyroidism and hypogonadotropism. The
2 Clinical symptoms of hypocalcemia are protean and in- caused most commonly by high phosphate content in milk. difference between the two forms is in Gs- protein levels in red
clude: neuromuscular changes (tetany), central nervous system blood which is reduced in type 1a and normal in type 1c. Type 1b is
manifestations (generalized or focal seizures, psychological distur- 8 Familial hypoparathyroidism may be autosomal recessive, characterized by a normal phenotype and abnormal biochemical
bances, intracranial Ca deposits), bradyarrthmias, ocular involve- autosomal dominant or x-linked. In the autosomal-dominant type, tests.
ment (cataracts), dental abnormalities as well as skin changes (xero- there is a gain of function mutation in the CaSR, leading to hypocal-
dermatosis, alopecia). cemic hypercalciuria. Although serum PTH levels can be within the 16 PHP type 2 is characterized by markedly increased PTH
normal range, they are inappropriate for the degree of hypocalcemia. levels with urinary cAMP levels elevated both before and after PTH
3 In patients with calcipenic rickets, additional biochemical infusion.
findings are hypophosphatemia, elevated levels of serum alkaline 9 Aplasia/hypoplasia of the parathyroid glands is often found
phosphatase and secondary hyperparathyroidism. Examining serum in DiGeorge anomaly, which includes, in addition to parathyroid hy-
levels of vitamin D metabolites [25(OH)D and 1,25(OH)2D3] are impor- poplasia, thymic hypoplasia, cardiac abnormalities (all of which are Selected reading
tant in the work-up of the child with hypocalcemic rickets. Hereditary related to the structures arising from the 3rd and 4th brachial arches),
forms of hypophosphatemic rickets are not associated with distur- facial dysmorphism, and often, a gene deletion in 22 q11. Velocardio- Al-Jenaidi F, Makitie O, Grunebaum E, Sochett E: Parathyroid gland
bances in serum calcium levels. facial syndrome, or other isolated 22q11 gene mutations may pro- dysfunction in 22q11.2 deletion syndrome. Horm Res 2007;67:
duce hypoparathyroidism as well. The hypocalcemia in these syn- 117122.
4 If serum 25(OH)D levels are low, vitamin D-deficient rickets dromes may disappear spontaneously in young children, although it Gelfand IM, Eugster EA, DiMeglio LA: Presentation and clinical
is suspected. The differential diagnosis includes vitamin D-poor diet, may return later in life. progression of pseudohypoparathyroidism with multi-hormone
insufficient exposure to sunlight (especially in dark-skinned infants), resistance and Albright hereditary osteodystrophy: a case series.
malabsorption secondary to gastrointestinal or hepatobiliary dis- 10 Hypoparathyroidism may occur in various syndromes in- J Pediatr 2006;149:877880.
eases and due to medications that alter normal 25(OH)D metabolism. cluding Kerns Sayre syndrome and other mitochondrial cytopathies, Hochberg Z: Vitamin-D-dependent rickets type 2. Horm Res 2002;
auto-immune endocrinopathy type 1 (associated with systemic can- 58:297302.
5 When serum 25(OH)D levels are normal, genetic disorders didiasis and Addison disease), Kenney-Caffey syndrome (small stat- Holick MF: Resurrection of vitamin D deficiency and rickets.
in vitamin D metabolism are suspected. This form of rickets [previ- ure, tubular long bones, osteosclerosis) and others. J Clin Invest 2006;116:20622072.
ously known as vitamin D-dependent rickets (VDDR)] can be further Langman CB: Disorders of phosphorus, calcium and vitamin D; in
differentiated by measuring serum levels of 1,25(OH)2D3. In 1- hy- 11 Secondary hypoparathyroidism is seen most commonly Avner ED, Harmon WE, Niaudet P (eds): Pediatric Nephrology, ed 5.
droxylase deficiency (called in the past VDDR type 1) serum levels of after (para)-thyroidectomy. Other reasons of secondary hypopara- Philadelphia, Lippincott Williams & Wilkins, 2004, pp 237254.
1,25(OH)2D3 are low or absent due to a mutation in the gene encoding thyroidism include infiltrative lesions such as tumors, hemosiderosis Thacher TD, Fischer PR, Pettifor JM: Rickets: vitamin D and calcium
the enzyme 1-hydroxylase which converts 25(OH)D to 1,25(OH)2D3 (thalassemia) and copper deposition (Wilson disease). deficiency. J Bone Miner Res 2007;22:638.
in the kidney. Administration of an active vitamin D analogue is the
therapy of choice. In vitamin D-resistant rickets (originally termed 12 The combination of hypocalcemia, hyperphosphatemia and
VDDR type 2) serum levels of 1,25(OH)2D3 are high. This rare entity is elevated serum creatinine concentration suggests the presence of
caused by end-organ resistance (often associated with alopecia) to secondary hyperparathyroidism secondary to chronic kidney dis-
vitamin D actions due to mutations in the vitamin D receptor gene. ease. For details see Renal osteodystrophy.
Therapy consists of high dose of 1,25(OH)2D3 as well as calcium sup-
plements. 13 PHP also known as Albright hereditary osteodystrophy is
characterized by hypocalcemia and hyperphosphatemia despite a
6 Severe hypomagnesemia, via its effect on the Ca2+/Mg2+ normal or even elevated serum levels of PTH. There are several
sensing receptor (CaSR), can lead to hypocalcemia through both a types of this genetic disorder which are caused by defects in the ad-
93
decrease in PTH production or secretion and end organ resistance to enylate cyclase system necessary for the PTH-receptor normal func-
this hormone. tion in end organs. PHP is usually a part of the McCune-Albright he-
reditary osteodystrophy the main clinical features of which are short
stature, psychomotoric and mental retardation, brachydactyly and
/
Hypercalcemia Symptoms 0
94 Serum PTH 1
Low Normal/increased
No Increased
Tumor
PTHrpM
No Yes
Syndromatic features
No Yes
Phosphate depletion 2 Jansen osseous dysplasia : Tumor hypercalcemia ; Vitamin D intoxication < Primary/tertiary Familial hypocalciuric
Vitamin A intoxication 3 Williams syndrome hyperparathyroidism = hypercalcemia >
High-dose hydrochlorothiazide therapy 4 Infantile idiopathic hypercalcemia
Adrenal insufficiency 5
Hypo-/hyperthyroidism 5
Immobilization 6
Hypophosphatasia 7
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Divalent ion metabolism B. Hoppe G. Ariceta C.B. Langman Hypercalcemia
Divalent ion metabolism C.B. Langman G. Ariceta B. Hoppe Hypophosphatemia
/
Hypophosphatemia Symptoms 0
96
P depletion
Urine P 2
Increased Reduced
PTH
Normal/low High
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1 Serum P level is continuously declining with 5 In generalized proximal tubulopathy (termed 7 For details on hyperparathyroidism, see Hy-
age, and thus the definition of hypophosphatemia is Fanconi syndrome), excessive phosphaturia may be percalcemia and Renal osteodystrophy. Of note, after
age-dependent. Hypophosphatemia in adolescents associated with glycosuria, aminoaciduria, and bicar- long-standing hyperparathyroidism is resolved there
and adults is defined as a serum P level <2.5 mg/dl. bonaturia. For details, see Faconi syndrome and Meta- is an increased avidity of bone for Ca and P, termed
Normal values in other age groups include: infants: bolic Acidosis. After the relief of obstructed kidneys, hungry bone syndrome (see below).
mean 6.5 mg/dl, range 4.87.4; toddlers: mean excessive urinary losses of water and minerals includ-
5.0 mg/dl, range 4.55.8 mg/dl; children: mean 4.4 mg/ ing P, can be observed (postobstructive diuresis). A 8 Any condition leading to P deprivation may
dl, range 3.55.5 mg/dl. similar phenomenon might be seen during the diuretic lead to hypophosphatemia with low urinary P concen-
phase of acute tubular necrosis. High P excretion in tration. In addition, intestinal disorders leading to mal-
2 Hypophosphatemia may be asymptomatic or urine can also be observed after the administration of absorption will show the same abnormalities in P level.
associated with various symptoms. Symptoms result drugs such as glucocorticoids and diuretics (acetazol- Calcium carbonate and other drugs that can bind to
from decreased intracellular ATP level and impaired amide, thiazides). the P in the diet, may lead to hypophosphatemia.
oxygen delivery to tissues, and may include anorexia, After long-standing hyperparathyroidism (primary or
vomiting, muscle dysfunction (paraesthesias, hypore- 6 Selective urinary P wasting is seen in several secondary) has resolved, increased avidity of bone for
flexia, proximal myopathy), rickets or osteomalacia as genetic disorders collectively called hypophospha- Ca and P may lead to hypophosphatemia and hypocal-
well as hematologic disorders. Severe P deficit associ- temic rickets. XLH is characterized by reduced recla- cemia. This disorder is termed hungry-bone syn-
ated with acute shift of P into the cells can lead to life- mation of filtered phosphorus by the proximal tubule, drome and it is usually transient in nature.
threatening events: cardiac failure with ventricular ar- and normal levels of 1,25(OH)2D which are inappropri-
rhythmias, hypotension, rhabdomyolysis, respiratory ate for the degree of hypophosphatemia. XLH is
failure, or coma. caused by mutations in the PHEX gene. Autosomal Selected reading
dominant hypophosphatemic rickets result from muta-
3 More than 99% of P is found in the intracel- tions in the gene encoding FGF-23, a potent phospha- Cho HY, Lee BH, Kang JH, Ha IS, Cheong HI, Choi Y:
lular compartment and only less than 1% is extracel- turic agent. This mutation renders the FGF-23 resistant A clinical and molecular genetic study of hypophos-
lular. Most P content in the body is in bone. Acute to normal proteolytic cleavage and hence, exagger- phatemic rickets in children. Pediatr Res 2005;58:
shifts from extra- to intracellular space may reduce ates its phosphaturic action, and that of reducing the 329333.
serum P leading to hypophosphatemia. Increased 25(OH)D-1--OHase activity in the proximal nephron Hochberg Z: Vitamin-D-dependent rickets type 2.
carbohydrate intake stimulates insulin release which, mitochondria, too. Autosomal recessive XLH has re- Horm Res 2002;58:297302.
in turn, leads to P shift into cells. Thus, infusion of glu- cently been described to be due to mutations in DMP-1, Holick MF: Resurrection of vitamin D deficiency and
cose, fructose, lactate or amino acid salts (especially and seemingly, elevations in FGF23 level as well. In rickets. J Clin Invest 2006;116:20622072.
during refeeding malnourished patients or in diabetic HHH, the genetic abnormality is due to mutations in Kollars J, Zarroug AE, van Heerden J, Lteif A,
ketoacidosis) may lead to hypophosphatemia. Respira- the gene encoding NaPi IIc, a Na-P cotransporter of Stavlo P, Suarez L, Moir C, Ishitani M, Rodeberg D:
tory alkalosis, as a result of acute hyperventilation (e.g. the proximal tubule. In contrast to XLH and autosomal- Primary hyperparathyroidism in pediatric patients.
anxiety) or in a variety of respiratory disorders, may dominant or -recessive hypophosphatemic rickets, se- Pediatrics 2005;115:974980.
lead to hypophosphatemia. Various drugs such as in- rum levels of 1,25(OH)2D in HHH are elevated, leading Langman CB: Disorders of phosphorus, calcium and
sulin, glucagon, androgens and -adrenergic agonists to hypercalciuria. All of these disorders, if left untreat- vitamin D; in Avner ED, Harmon WE, Niaudet P (eds):
have a similar effect. ed in children, will lead to rickets and short stature. Pediatric Nephrology, ed 5. Philadelphia, Lippincott
Various forms of vitamin D related rickets lead to hypo- Williams & Wilkins, 2004, pp 237254.
4 With a normal dietary intake of P, 1520% of phosphatemia. In oncogenic osteomalacia, there is
the filtered P is excreted in the final urine. Total body P excessive production of FGF-23 by various tumors
deficit, in the presence of a normal functioning kidney, leading to hypophosphatemia. Phosphaturia and hy-
will maximally increase tubular reabsorption of this pophosphatemia may occur in 70% of patients follow-
mineral and will reduce P excretion to nil. ing renal transplantation within the first year, and be
either transient or permanent. Persistent secondary
hyperparathyroidism, corticosteroid therapy and in-
trinsic tubular dysfunction of the graft are possible
factors involved in this abnormality. Persistence of el-
97 evated levels of FGF23 after kidney transplantation
may be responsible for persistent hypophosphatemia.
/
Hyperphosphatemia Symptoms 0
98 Urine P 1
Reduced Increased
Serum creatinine
Increased Normal
Plasma Ca
Normal Low
PTH
Normal/high Low
/
Hypomagnesemia Symptoms 0
100 FEMg2+ 1
Renal losses
Decreased intake 2 Altered Mg2+ distribution 3 Gastrointestinal losses 4
Acquired 5 Genetic 6
Malnutrition Hungry bone syndrome Malabsorptive syndromes (celiac, IBD) Postobstructive diuresis Gitelman syndrome
Alcoholism Refeeding Diarrhea Recovery from ATN Familial hypomagnesemia,
Low-magnesium food Diabetic ketoacidosis Short bowel syndrome Renal transplantation hypercalciuria and nephrocalcinosis
Parenteral fluids Bowel resection Drugs Isolated hypomagnesemia
Laxative abuse Loop/thiazide diuretics (autosomal-dominant, autosomal-recessive)
Primary intestinal hypomagnesemia Aminoglycosides Autosomal-dominant hypoparathyrodism
Amphotericin B
Cisplatinum
Hypercalciuria
102 Urolithiasis, hematuria, dysuria
Normal Urolithiasis
History and physical examination 0 Nephrocalcinosis
Family history 1
Dietary history 2
Medication history 3
Defer evaluation if patient has urinary tract infection 4
Blood tests
Electrolytes, bicarbonate, pH, calcium, phosphorus,
magnesium, PTH and vitamin D metabolites
Repeat urinary testing including 24-hour collection for
calcium, sodium, citrate, creatinine:
onsider testing uric acid and oxalate levels 5
Nephrolithiasis/urolithiasis
104 Symptoms/signs of urinary stone /
Imaging 2
Stone passed and Stone identified in No stone identified but High fluid intake 5
recovered urinary tract history suggestive of stone Reduced sodium intake 5
+ + + + +
Urologic or Complete metabolic evaluation 3
surgical consultation Serum creatinine, calcium, bicarbonate, Hypercalciuria Hyperoxaluria Uric acid Cystinuria Struvite
uric acid, potassium, phosphorus, lithiasis
magnesium, PTH and vitamin D metabolites,
if indicated
24-hour urine volume, calcium, creatinine,
oxalate, uric acid, sodium, citrate, High K+ and Bicarbonate/citrate Prevent/treat
Options include
or random urine calcium/creatinine, low oxalate diet (urine pH 7.07.5) infection
observation, ESWL,
oxalate and uric acid Citrate when Allopurinol
surgical removal
indicated Avoid excessive
Consider thiazides purines
Stone analysis 4
Avoid oxalate-rich foods Bicarbonate/citrate
Supplemental citrate, (urine pH 7.07.5)
Mg2+ and orthophosphate MPG
Consider thiazides
Consider pyridoxine
Calcium oxalate Cystine Struvite Uric acid Avoid vitamin C supplements
Calcium phosphate
Complete metabolic Urine cystine Urine culture Urine and serum uric Evaluation positive for
evaluation 3 acid and creatinine stone disease
/
Oliguria/anuria
106
Oliguria Anuria
Rehydration 1 Furosemide 4
15 mg/kg
Fluid challenge 2
furosemide
Prerenal failure No diuresis Oliguric intrinsic Non-oliguric intrinsic Anuric intrinsic Postrenal failure
acute renal failure acute renal failure acute renal failure
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1 Oliguria is defined as the excretion of less 6 In some cases of oliguric acute renal failure,
Selected reading
than 400 ml/m2 body surface area of urine. Anuria is high-dose furosemide (up to 5 mg/kg) may initiate di-
the complete cessation of urine output. Oligouria/an- uresis. Patients with nonoliguric renal failure have a Andreoli SP: Clinical evaluation and management
uria may be one of the first signs of impaired renal generally better prognosis and the management of of acute renal failure; in Avner ED, Harmon WE,
function. The purpose of this algorithm is to give the these patients in terms of drug and nutrition adminis- Niaudet P (eds): Pediatric Nephrology, ed 5.
clinical approach to the oligo-anuric child. The differ- tration is easier. If the child remains oligoanuric, fluid Philadelphia, Lippincott/Williams & Wilkins, 2004,
ential diagnosis of the conditions leading to oligo-an- intake should be restricted to 400 ml/m2 + ongoing pp 12331252.
uria are described in the algorithms on Neonatal losses (urine, vomiting, gastric drainage, etc.) of hypo- Bailey D, Phan V, Litalien C, Ducruet T, Merouani A,
acute renal failure and Acute renal failure (child/ado- tonic fluids. Lacroix J, Gauvin F: Risk factors of acute renal failure
lescent). in critically ill children: A prospective descriptive
7 In cases of intrinsic renal failure, apart from epidemiological study. Pediatr Crit Care Med 2007;8:
2 In the child with oliguria, assessment of treating the specific condition, fluids, electrolytes and 2935.
volume status is vital in order to proceed with the acid-base abnormalities should be addressed. If pos- Hui-Stickle S, Brewer ED, Goldstein SL: Pediatric
work-up. sible, nephrotoxic drugs should be discontinued. ARF epidemiology at a tertiary care center from
These include agents such as NSAIDs, ACE inhibitors, 1999 to 2001. Am J Kidney Dis 2005;45:96101.
3 4 When dehydration is present: the fluid angiotensin II AT1 receptors blockers, amphotericin B, Krause I, Cleper R, Eisenstein B, Davidovits M:
deficit should be corrected initially by administration aminoglycoside antibiotics and vancomycin. If the Acute renal failure, associated with non-steroidal
of 2040 ml/kg of isotonic fluid over 2 h. The use of conservative measures mentioned above fail to re- anti-inflammatory drugs in healthy children.
isotonic saline is a safe method of rehydration. If diure- store renal function or if complications of severely re- Pediatr Nephrol 2005;20:12951298.
sis does not ensue, consider the administration of a duced GFR occur (hyperkalemia, metabolic acidosis, Mannix R, Tan ML, Wright R, Baskin M: Acute
colloid such as plasma or albumin at a rate of 20 ml/kg pulmonary edema, pericarditis, hypertension) RRT pediatric rhabdomyolysis: causes and rates of renal
over 2 h. If the above measures do not initiate diuresis, must be started. The choice of RRT to be used (perito- failure. Pediatrics 2006;118:21192125.
furosemide at a dose of 25 mg/kg may be attempted. neal dialysis, hemodialysis or hemofiltration) depends
on a variety of factors.
5 Once normal urine output has been achieved,
maintenance fluid therapy should begin either intrave- 8 Whenever urinary tract obstruction is diag-
nously or orally: for the first 10 kg bodyweight, 100 ml/ nosed, the obstruction should be promptly relieved.
kg. For the next 10 kg body weight, 50 ml/kg. For each Of note, polyuria (postobstructive diuresis) and elec-
kg above 20 kg, 20 ml/kg. trolyte abnormalities are common after the relief of
obstruction.
107
/
Neonatal acute renal failure
108 Assess volume status 1 Gestational/postnatal history 0
Clinical manifestations
Blood chemistry
Urinalysis and urine indices
Renal US
Hypovolemia Euvolemia Hypervolemia
Rehydration 2
Replacement of blood loss Consider furosemide 4
Restoration of cardiac output
Diuresis No diuresis
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1 Acute renal failure is observed in 824% of attempted. In hypotensive neonates, dopamine may
Selected reading
neonates admitted to neonatal intensive care units. be used at a dose of 24 g/kg/min. Higher doses
Although acute renal failure in a neonate is a serious (<10 g /kg min) may produce renal vasoconstriction Andreoli SP: Acute renal failure in the newborn.
and life-threatening condition, prognosis in neonates by an -adrenergic agonist effect. Semin Perinatol 2004;28:112123.
with nonoliguric acute renal failure is excellent. In con- Cuzzolin L, Fanos V, Pinna B, di Marzio M, Perin M,
trast, mortality rates in neonates with oliguric acute 5 Any condition that causes hypovolemia, hy- Tramontozzi P, Tonetto P, Cataldi L: Postnatal renal
renal failure are high, ranging from 25 to 80%. potension or hypoxemia may decrease renal perfusion function in preterm newborns: a role of diseases,
and lead to prerenal failure. If severe and of long dura- drugs and therapeutic interventions. Pediatr
2 Detailed history (pre- and postnatal) and tion, prerenal failure may lead eventually to intrinsic Nephrol 2006;21:931938.
physical examination are mandatory in the work-up of renal damage. Gouyon JB, Guignard JP: Management of acute
the neonate with acute renal failure. Pre- and postnatal renal failure in newborns. Pediatr Nephrol 2000;14:
history should include information regarding: abnor- 6 In some cases of oliguric acute renal failure, 10371044.
mal perinatal sonogram findings (oligohydroamnios, high-dose furosemide (up to 5 mg/kg) may initiate di- Guignard JP, Drukker A: Why do newborn infants
hydronephrosis, kidneys size, kidneys location, ap- uresis. have a high plasma creatinine? Pediatrics 1999;
pearance of the parenchyma and appearance of the 103:e49.
urinary bladder), maternal or neonatal drug use (ACE 7 The main conditions leading to intrinsic renal Toth-Heyn P, Drukker A, Guignard JP: The stressed
inhibitors, angiotensin II AT1 receptor antagonists, failure in the neonatal period are congenital renal neonatal kidney: from pathophysiology to clinical
NSAIDs, aminoglycosides, amphotericin B, etc.), previ- anomalies and acute tubular necrosis. The most com- management of neonatal vasomotor nephropathy.
ous intrauterine fetal demise or stillbirth or congenital mon congenital kidney malformation leading to renal Pediatr Nephrol 2000;14:227239.
kidney malformations in family relatives. failure is bilateral renal agenesis/dysgenesis. This ab-
Physical examination should include: vital signs normality is commonly associated with Potter syn-
(tachypnea/dyspnea, hypotension/hypertension, drome (oligohydroamnios, pulmonary hypoplasia and
tachycardia/irregular pulse), cardiac murmur or gallop, distinctive facies). The manifestations of PKD (either
palpation of femoral pulses, signs of dehydration/hy- autosomal-dominant or autosomal-recessive) can
pervolemia, abnormal neurologic findings or abdomi- range from intrauterine fetal demise or neonatal ESRD,
nal masses. The initial evaluation of the neonate with to slowly deteriorating kidney function leading to
acute renal failure includes the following tests: serum ESRD later in life. For further details see Cystic kid-
levels of creatinine, BUN, electrolytes (potassium, so- neys. Renal ischemia (usually due to birth asphyxia,
dium, magnesium, calcium, phosphorus), albumin and septic shock, massive bleeding or heart failure) can
bicarbonate. Urine sample for sediment examination, lead to either medullary, papillary or most commonly
electrolytes and creatinine levels, osmolality and cul- cortical necrosis. Although prognosis is generally
ture. The urine sodium level and osmolality are very poor, the extent of necrosis, duration of oliguria, and
helpful in the differential diagnosis of acute renal fail- severity of associated conditions determine the ulti-
ure (table). In addition to the laboratory tests men- mate prognosis. The most common drugs causing re-
tioned above, a renal sonogram is mandatory in every nal impairment in the newborn period are aminoglyco-
neonate with acute renal failure. Additional tests sides and NSAIDs.
should be reserved for the subsequent evaluation de-
pending on the suspected condition (as outlined in the 8 The most common obstructive congenital
algorithm). malformations leading to neonatal acute renal failure
are bilateral UPJ obstruction, bilateral uretero-vesicle
3 Assessment of the volume status of the junction obstruction and posterior urethral valves.
neonate with acute renal failure according to the For details, see Fetal hydronephrosis.
physical examination and laboratory work-up
mentioned above is vital in order to proceed with
the work-up.
Table. Diagnostic urinary indices
109 4 When dehydration is present: the fluid deficit Prerenal Intrinsic
should be corrected initially by administration of
Urinalysis normal >5 RBC/HPF
2040 ml/kg of isotonic fluid over 2 h. The use of an Uosm, mosm/kg H2O >400 <400
isotonic saline is a safe method of rehydration. If UNa, mmol/l <30 >60
/
Acute renal failure (child/adolescent)
110 Assess volume status 1 History 0
Clinical manifestations
Blood chemistry
Urinalysis and urine indices
Renal US
Hypovolemia Euvolemia Hypervolemia
CBC, Serum: CBC, CPK, LDH, albumin, C3, C4, ANA, ANCA, Metabolic stones profile
Liver function tests anti-GBM ab, hepatitis serology, myoglobin Abdominal US/CT
Chest X-ray Urine: eosinophils, myoglobin
ECG Renal US + Doppler
Echocardiogram Kidney biopsy
/
Chronic renal failure
112 Etiology 0
Reduce proteinuria 1
Control blood pressure
Metabolic control
Optimize nutrition
Treat ESRD 2
Control hypertension Adequate nutrition Iron/folic acid supplements Identify bone disorder Treat blood-borne Physiotherapy
Prevent fluid overload Vitamin supplements Treat carnitine deficiency Control P, Ca2+, PTH levels infections Treat learning disabilities
Treat hyperlipidemia Correct acidosis and rHuEpo treatment Correct acidosis and Immunizations Treat speech/hearing
Treat carnitine deficiency sodium depletion sodium repletion impairments
Prevent renal bone disease Sociofamilial support
rhGH treatment
Dialysis
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1 Chronic renal failure is defined as an irreversible reduction should include careful monitoring of weight and height, anthropo- 11 When ESRD (GFR <510 ml/min/1.73 m2) has been reached,
in GFR. When the chronic renal failure is severe enough to mandate metric measurements and monitoring of the daily intake of calories, RRT is indicated. The choice of the mode of RRT (hemodialysis or
the initiation of dialysis, it is termed ESRD. The prevalence of chronic protein, electrolytes, minerals, vitamins and trace elements recom- peritoneal dialysis) depends on a variety of disease-, patient- and
renal failure in children is approximately 18 per million children. The mended for the child with ESRD. Recombinant human growth hor- family-related factors. Hemodialysis is performed in the hospital 36
purpose of this algorithm is to discuss the major treatment strategies mone (rhGH) therapy should be considered when indicated. times per week depending on the childs age and condition. Perito-
and complications of chronic renal failure in children. For details on neal dialysis is usually performed at home using an automated ma-
the various disorders leading to chronic renal failure and ESRD, see 7 In children with chronic renal failure, hemoglobin levels de- chine (automated peritoneal dialysis).
appropriate algorithms. crease when the GFR is below 35 ml/min/1.73 m2 body surface area.
The most important cause for anemia in these children is inadequate 12 The ultimate goal of therapy in the child with ESRD is renal
2 The most common causes of chronic renal failure in chil- erythropoiesis secondary to low erythropoietin levels normally pro- transplantation. The options of donations for transplantation include
dren are congenital malformations (including aplastic/hypolastic/ duced by the kidneys. Other causes of anemia in ESRD include poor living-related, living-nonrelated and deceased donors. Renal trans-
dysplastic kidneys, reflux nephropathy and obstructive uropathies), iron intake, blood loss in children treated with hemodialysis, carni- plantation in children has become a well-established therapy. The
which account for 3540% of the cases. FSGS and other chronic glo- tine deficiency and hyperparathyroidism. The follow-up of anemia in graft survival rates have improved dramatically with current 5-year
merulopathies account for approximately 20% and metabolic/genetic children with ESRD includes blood testing for CBC, iron, ferritin and graft survival rates of 83% and 73% for living-related and deceased
diseases for an additional 10% of cases. transferrin levels checked at regular intervals. The recommended donors, respectively.
hemoglobin levels in children with ESRD are 1112 g/dl. Treatment
3 In the child with chronic renal failure who has not reached strategies of the anemia include iron, folic acid and, when indicated,
ESRD the goal is to halt the deterioration in renal function. Antipro- carnitine supplements. Recombinant erytheropoietin administration
Selected reading
teinuric agents such as ACE inhibitors and angiotensin II receptor has become the mainstay of the management of anemia in these
blockers have been shown to reduce the proteinuria in chronic renal children. Transfusion of RBCs is occasionally required. It should be Bakr A, Amr M, Sarhan A, Hammad A, Ragab M, El-Refaey A,
failure and thereby slow the progression of renal disease. In a child emphasized, however, that multiple transfusions of RBCs increase El-Mougy A: Psychiatric disorders in children with chronic renal
treated with these agents, it is important to monitor serum creatinine the risk of renal graft rejection following transplantation. failure. Pediatr Nephrol 2007;22:128131.
and potassium levels. Hypertension in children with chronic renal Filler G: Renal transplantation: literature review 2004-2005.
failure is caused by various factors including sodium and water re- 8 For details on Renal Bone Disease, see appropriate Pediatr Transplant 2006;10: 418428.
tention, activation of the renin-angiotensin-aldosterone system and algorithm. Fine RN, Whyte DA, Boydstun II: Conservative management of
sympathetic overactivity. Hypertension is a major pathogenic factor chronic renal insufficiency; in Avner ED, Harmon WE, Niaudet P
in the progression of chronic renal failure. For treatment of hyperten- 9 Children with ESRD are prone to develop infections. Rea- (eds): Pediatric Nephrology, ed 5. Philadelphia, Lippincott
sion, see Pediatric Hypertension. Metabolic control and adequate sons for this tendency include immune system dysregulation, in- Williams & Wilkins, 2004, pp 12911312.
nutrition are very important measures in the care of the child with dwelling catheters and treatment with immunomodulatory drugs. Mahan JD, Warady BA, the Consensus Committee: Assessment
chronic renal failure (see below). Meticulous handling of catheter and dialysis equipment as well as and treatment of short stature in pediatric patients with chronic
high index of suspicion for signs of infection should be exercised. kidney disease: a consensus statement. Pediatr Nephrol 2006;21:
4 ESRD has major adverse effects on the child afflicted with Follow-up of children with ESRD should include serological blood 917930.
this condition. A multidisciplinary approach is mandatory in the tests performed periodically to check the immunological status of Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury
management of these children in order to treat the variety of physical these children and to exclude viral infections such as HIV, hepatitis B PR, Daniels SR: Progression of left ventricular hypertrophy in
and developmental complications of ESRD and to maintain normal and C, varicella zoster, CMV and EBV. In addition, immunization ac- children with early chronic kidney disease: 2-year follow-up study.
lifestyle in these children. cording to the specific recommendations for children with chronic J Pediatr 2006;149:671675.
renal failure should be pursued. Schroder CH, European Pediatric Peritoneal Dialysis Working
5 The main cardiovascular complication in children with Group: The management of anemia in pediatric peritoneal
ESRD is left ventricular failure secondary to hypertension. Other car- 10 ESRD in children and its complications can lead to severe dialysis patients: guidelines by an ad hoc European committee.
diovascular complications include nonhypertrophic cardiomyopathy developmental handicaps, hearing and language disturbances as Pediatr Nephrol 2003;18:805809.
secondary to carnitine deficiency, hyperlipidemia, and, rarely, car- well as psychological and emotional disorders. Academic achieve-
diac arrhythmias. There is accumulating evidence that morbidity ments in children with ESRD are often less than optimal.
from cardiovascular complications in children with ESRD is higher They also have more neurologic deficits, microcephaly, seizures and
than previously recognized and may have serious, long-term effects hypotonicity than their normal peers. Untreated uremia, hearing im-
on the health of these children. pairments (secondary to adverse reactions of drugs), prolonged hos-
pitalization periods and, in the past, aluminum toxicity are important
113 6 Growth retardation is very common in children with chronic causative factors in these impairments. To prevent or minimize these
renal failure and ESRD. Growth failure in these children is caused by impairments, aggressive control of uremia, adequate nutrition and
metabolic acidosis, sodium depletion, inadequate nutrition, bone avoidance of ESRD-related complications as well as a team work of
disease and abnormalities in the growth hormone axis. Dietary con- the pediatric nephrologist, family physician, social worker, physio-
/
Renal osteodystrophy
114 Clinical manifestations 0
Blood chemistry
Bone films
Bone biopsy
Bone pain, calcifications Bone pain, pathologic fractures Bone deformities, bone pain
PhosphorusMCa2+mN, PTHM Ca2+Malkaline phosphatasemPTHm Phosphorusmalkaline phosphataseM
Subperiosteal erosions Metaphyseal widening
Dietary phosphate restriction 2 Reduce PTH suppression 4 Phosphate and calcium supplements 6
Phosphate binders Active vitamin D analogues
Active vitamin D analogues
Calcium-sensing-receptor agonist
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Fanconi-Bickel glycogenosis 60, 62 High-dose hydrochlorothiazide therapy 94 Intracranial hypertension 76
Fanconi-Bickel syndrome 58 Histidinuria 54 Intrinsic renal failure 108, 110
Fat deposition 44 HIV nephropathy 20 Ischemia 44
Fetal lobulation 42, 48 Hodgkin/non-Hodgkin lymphoma 42 Isolated cystinuria 54
Fever 74 Horseshoe kidney 48 Isolated glycinuria 54
Fibrosis 110 Human immunodeficiency syndrome 10 Isolated hereditary renal glycosuria 58
Focal segmental glomerulosclerosis 10, 12, 90, 112 Hungry bone syndrome 96, 100 Isolated hypomagnesemia 100
Fractures 114 Hydronephrosis 4 Isolated lysinuria 54
Fungal ball 110 Hydrops fetalis 90
Fungal bezoar 108 1--Hydroxylase deficiency 70 Jansen chondrodysplasia 96
Hypercalcemia 50, 52, 64, 102
J Jansen osseous dysplasia 94
G Galactosemia 60, 62 Hypercalciuria 44, 104 Jansen syndrome 70
Gastric drainage 76, 80 Hyperdibasic AA type I 54 Juvenile nephronophthisis 46
Gastrocystoplasty 86 Hyperkalemia 60
Gastrointestinal bleeding 82 Hyperkalemic distal renal tubular acidosis 84 K Kawasaki syndrome 18
Genetic cobalamin C defect 20 Hyperosmolality 82 Ketonuria 72
Giggle/stress incontinence 30 Hyperostosis 98
Gitelman syndrome 64, 76, 80, 86, 100
Glomerulocystic kidney disease 42
Hyperoxaluria 36, 44, 104, 112
Hyperparathyroidism 62, 96
L Laceration 34
Laxative abuse 100
Glomerulonephritides 52, 110 Hypertension 76 Laxatives 98
Glomerulonephritis 32, 42, 44 Hyperthyroidism 50, 52, 94, 98 Lazy bladder 30
Glucocorticoid deficiency 72 Hypertrophy 42 Lesch-Nyhan syndrome 68
Glucocorticoid-remediable aldosteronism 52, 76, 80 Hypervolemia 106, 108, 110 Leukemia 68, 84
Glucocorticoids 52, 96 Hypoadrenalism 88 Leukocyte esterase 22
Glucose infusion 96 Hypoaldosteronism 88 Licorice ingestion 76, 80, 86
Glucose-6-phosphatase deficiency 68 Hypocalcemia 64 Liddle syndrome 52, 76, 80, 86
Glucose-galactose malabsorption 58 Hypocomplementemic urticarial vasculitis 18 Liver disease 70, 88
Glucosuria 62 Hypokalemia 60 Liver failure 84
Glue sniffing 60, 62 Hypomagnesemia 92, 102 Loaded colon 30
Glycogen storage disease type 1 42, 60, 68 Hyponatremic hypertensive syndrome 88 Loin pain hematuria syndrome 4
Goodpasture syndrome 4, 14 Hypoparathyroidism 68, 86, 92, 98 Loop 86
Gordon syndrome 50, 52, 60, 82, 84 Hypophosphatasia 94 Lowe syndrome 60, 62
Guillain-Barr syndrome 52 Hypophosphatemia 102 Lower limb reflexes 30
Hypophosphatemic rickets 62, 70, 96 Low-magnesium food 100
H Hartnup disease 54
Heart failure 72, 108
Hypoplasia/dysplasia 40, 112
Hyporeninemic hypoaldosteronism 60, 82, 84
Lung hemorrhage 14
Lupus nephritis 4, 6
Heavy metal poisoning 52, 60, 62 Hypothyroidism 72, 94 Lymphangiectasis 48
Hematoma 48, 110 Hypovolemia 76, 106, 108, 110 Lymphoma 68
Hematuria 4 Lysinuric protein intolerance 54
Hemoglobinuria 42, 108 I Idiopathic crescentic glomerulonephritis 90
Hemolytic-uremic syndrome 4, 20, 52, 90,
110, 112
Idiopathic Fanconi syndrome 62
Idiopathic hypercalciuria 102
M Malabsorption 88
Malabsorptive syndromes 100
Hemophilia 42 Idiopathic nephrotic syndrome 90 Malnutrition 88, 90, 100
Henoch-Schnlein purpura 6, 18 Idiopathic renal hypouricemia 66, 72 Marfan syndrome 60
Hepatic failure 90 IgA nephropathy 4 Marked volume depletion 60
Hepatitis B glomerulonephritis 12 Imperforated prepuce 108 Maternal drug abuse 50
117 Hepatitis C glomerulonephritis 12 Inadequate fluid intake 108, 110 Medullary sponge kidney 44, 46
Hepatorenal syndrome 16, 110 Infantile idiopathic hypercalcemia 94 Melena 88
Hereditary fructose intolerance 60, 62 Insensible losses 74, 88 Membranoproliferative glomerulonephritis 6, 14,
Hereditary malformation syndrome 46 Insulin deficiency 82 16, 90
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Renin-secreting tumor 80, 86 T Takayasu arteritis 18, 52 V Vascular congestion 44
Renovascular disease 80 Tamm-Horsfall protein 42, 44 Vascular disorders 108
Respiratory alkalosis 96 Tertiary hyperparathyroidism 94 Vascular pathology 88
Retroperitoneal hematoma 34 Thalassemia 42 Vasculitides 52
Retroperitoneal process 110 Thiazides 86 Vasculitis 18, 36, 90, 110
Rhabdomyolysis 82 Thick-walled bladder 24 Vesicoureteral reflux 24, 26, 28, 42
Rhabdomyosarcoma 4 Thin basement membrane disease 16, 32 Vitamin A intoxication 94
Rheumatoid arthritis 60 Thromboembolism 50 Vitamin D 52
Rickets 114 Thrombotic thrombocytopenic purpura 20 Vitamin D depletion 70
Rubella 10 Tissue hypoperfusion and hypoxia 84 Vitamin D intoxication 50, 70, 94, 98
Total parenteral nutrition 50, 78, 96 Vitamin D-deficient rickets 92
S Salicylates 84
Salt-losing CAH 82
Transient neonatal hypercalcemia 94
Transluminal angioplasty 18
Vitamin D-related rickets 96
Vitamin D-resistant rickets 70, 92
Salt-losing nephropathy 72, 88 Tuberous sclerosis 42 Vomiting 72, 76, 80, 86, 108, 110
Salt-wasting (renal/adrenal disease) 110 Tubular disorders 8
Sarcoidosis 68, 94 Tubulointerstitial nephritis 4, 36, 110 W Water deprivation test 74
Sepsis 110 Tumor hypercalcemia 94 Wegeners granulomatosis 4, 12, 14, 18
Serum aldosterone 88 Tumor lysis syndrome 68 Williams syndrome 94
Severe loin pain 28 Tyrosinemia 60, 62 Wilms tumor 4, 42, 48, 50
Severe respiratory distress 108 Wilson disease 36, 60, 62
Short bowel syndrome 100 Umbilical artery catheter 52
Sickle cell disease 36, 42, 60, 82
U Urate nephropathy 44 Xanthinuria 44, 66
Sjogren disease 42 Ureteropelvic avulsion 34
X Xanthogranulomatous malakoplakia 48
Sjogren syndrome 60 Ureteropelvic junction obstruction 42 X-linked hypophosphatemic rickets 70
Skin nodules 18 Ureterosigmoidostomy 78, 80
Solid tumors 84 Uric acid excretion 66
Splenic compression 42 Uric acid lithiasis 104
Starvation 68 Urinary stone 104
Strenuous exercise 4 Urinary tract abnormalities 38
Struvite 104 Urinary tract obstruction 64
Subperiosteal erosions 114 Urine anion gap 60, 78, 84
Sweat test 86 Urine chloride 86
Sweating 74 Urinoma 48
Syndrome of inappropriate antidiuretic hormone Urolithiasis 102
secretion 66 Uromodulim disorders 68
Systemic lupus erythematosus 10, 12, 14, 16, 36,
60, 83, 90
Systemic manifestations 90
119
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SBE Subacute bacterial endocarditis
SCFE Slipped capital femoral epiphysis
S-Hcys Serum homocysteine
SIADH Syndrome of inappropriate antidiuretic
hormone secretion
SLE Systemic lupus erythematosus
SMX Sulfamethoxazole
Stx Shiga toxin
T4 Tyroxine
TAP Transluminal angioplasty
TBI Total body irradiation
TFA Thomsen-Friedenreich cryptantigen
TIN Tubulointerstitial nephritis
TINU Tubulointerstitial nephritis with uveitis
TMP Trimethoprim
TPN Total parenteral nutrition
TSH Thyroid-stimulating hormone
TTKG Transtubular potassium gradient
TTP Thrombotic thrombocytopenic purpura
121