Professional Documents
Culture Documents
Urine analysis;
physical exam
Appearance; colour, odour.
Sp Gravity; n= 1003 1030
Chemical exam; pH, protein, glucose, ketones, bl,
urobilinogen.
Microscopic exam; crystals, casts, cells, organisms.
NB; nitrite test detect G ve Bact.
leukocyte esterase detect WBC (5-15/HPF)
RBC casts acute GN ( nephritic)
wbc cast interstitial N, pyelon.
tubular cell cast ATN.
Granular cell cast chronic GN, pyelo.
hyaline proteinuria
fatty Nephrotic
hematuria = rbcs > 3.
pyuria = wbcs > 4.
Red urine
Hematuria.
Hemoglobinuria.
Myoglobinuria.
Porphyrins.
Drugs; MD, L-dopa, desferoxamine,
metronidazol. Cyclophosphamidehgic
cystitis, Beetroot,.
Orange brown; direct bil, drugs;
phenazopyridine, nitrofurantoin, Fe, B1,
rifampicin, phenytoin.
Functional proteinuria
Causes
fever.
Exercise.
Congestive heart failure (renal ischemiaAgII).
Orthostatic proteinuria;
- young male
- Regress in 5-10 yrs.
- Diagnosed by early morning sample & by 12
hrs ambulatory & 12 hrs overnight.
Lasix renogram
Non obstructive
dilatation
Outflow
delay
+++
Parenchymal Normal
transit time
(PTT) after
IVI of 40 mg = immediate fall in time
activity curve
frusemide
Obstructive
dilatation
+++
delayed
= .fall less
.does not fall
Renal biopsy
1.
2.
3.
4.
Indications;
Nephrotic S
Unexplained RF with normal Kid size.
Failure of recovery from ARF.
Asymptomatic prot., hematuria.
1.
2.
3.
4.
5.
1.
Contra indications;
Obese, oedema.
Uncontrolled HTN.
Bleeding tendency.
Shrunken kid.
Single kid except transplanted.
Complications;
Pain, hematoma, hematuria(in 20%, severe in 1-3%, need intervension
in 1;400)
AV aneurysm in in 20% but insignificant.
Infection
Mortality 0.1%.
2.
3.
4.
Glomerulopathies
Granular mesangial
Granular
Linear Capillary
Clinical Presentations
* Asymptomatic proteinuria
* Nephrotic syndrome
* Nephritic syndrome
* Hypertension
* Hematuria which may be microscopic or macroscopic
* rapidly progressive renal failure
* chronic kidney disease.
Hematuric Syndromes
(Isolated Hematuria,
nephritic, or RPGN)
Proteinuric Syndromes
(Isolated Proteinuria,
Nephrotic)
-Mesangioproliferative GN
(eg, IgA nephropathy)
-Membranoproliferative GN
-Mesangial proliferative GN
-Fibrillary glomerulopathies
-Membranous nephropathy
-Diffuse proliferative GN
-Diabetic glomerulosclerosi
(eg, post- streptococcal GN,
lupus nephritis WHO IV)
-Amyloidosis.
-Crescentic GN ( severe IC,
pauci-immune nephritis,
anti-GBM nephritis)
-Light-chain deposition
disease
normal
IgA Nephropathy
(Berger dis)
IgA Nephropathy
40 to 50 %
hematuria
No Treatment
Monitoring
/6 -12 m.
<10 %
30 to 40 %
CKD + proteinuria,
0.5 - 1g/day
Acute
or RPGN.
6-months course
of steroids
Combined immunosuppressives ;
prednisone + cyclophosphamide for 2 yrs.
As RPGN
Slide no 11
What is the
most common
glomerular
lesion on light
microscopy of
this patient
when a biopsy
is taken
Henoch-Schnlein purpura
distinguished clinically from IgA
nephropathy by;
- prominent systemic symptoms,
- a younger age (<20 years old),
- preceding infection, and
- abdominal complaints.
C/P; skin, arthritis, abd pain, Renal.
Ttt; arthralgias NSAIDs, severe abd pain,
renal steroids.
Poststreptococcal Glomerulonephritis
acute endocapillary proliferative glomerulonephritis
ages of 2 -14 years,
throat infections with particular strains of streptococci
(nephritogenic strains); After impetigo by 26 weeks
and 13 weeks after pharyngitis.
subepithelial "humps.
C/P; acute nephritic picture
C3 with normal levels of C4.
TTT; eradication of infection.
Postinfectious glomerulonephritis can occur in
patients with Subacute Bacterial Endocarditis ,
ventriculoatrial and ventriculoperitoneal shunts;
pulmonary, intra-abdominal, pelvic, or cutaneous
infections; and infected vascular prostheses.
ANCA associated GN
pauci-immune glomerulonephritis
C-ANCA= anti-proteinase 3 (PR3) in Wegener's
P-ANCA= anti-myeloperoxidase (MPO) more common
in microscopic polyangiitis, and Churg-Strauss
syndrome.
TTT;
Induction therapy usually includes some combination
of methylprednisolone, and cycloph.
plasmapheresis in case of pulm hge.
Maintenance, steroid tapering & give
cyclophosphamide for up to 2 years after remission.
1)
Idiopathic Crescentic GN
Renal-limited glomerular capillaritis Pauci-immune
crescentic GN.
Both pANCA and cANCA +ve.
2) Microscopic Polyangiitis
Renal + systemic vasculitis.
3) Wegener's Granulomatosis
Renal + vasculitis + granulomas
nasal ulcers, sinus granuloma, hemoptysis
CXR...... nodules , cavities.
Biopsy of involved tissue small-vessel vasculitis and
noncaseating granulomas.
4) Churg-Strauss Syndrome
Renal + vasculitis + granulomas + eosinophilia.
Asthma, fleeting pulmonary infiltrates
May be associated with leukotriene receptor antagonists.
Goodpasture Syndrome:
Causes of pulmonary-renal S;
1.
2.
3.
4.
5.
6.
Microscopic Polyangiitis.
Wegener's Granulomatosis.
Good pasture $.
SLE.
Churg-Strauss Syndrome.
HSP, cryo.
Membranoproliferative GN=mesangiocapillary GN
Types;
Type I Disease (Most Common)
1ry.
2ry; SBE, SLE, HCV, cryo, HBV, solid malignancy.
Type II Disease (Dense Deposit Disease)
C3 nephritic factor-associated
Partial lipodystrophy
Type III Disease
Idiopathic
Complement receptor deficiency
Pathology;
1.
2.
3.
4.
Subendothelial deposits
mesangioproliferative changes
mesangial interposition between the capillary BM and endothelial
cellsThickening of the GBM with a double contour .
lobular segmentation
TTT;
Long term alternate day steroids (prednisone 2
mg/kg) for one year, followed by slow tapering to
a maintenance dose of 20 mg every other day
for 3 to 10 years.
The role of aspirin and dipyridamole is unclear.
DD of MPGN;
cryoglobulinemia
Lupus nephritis class IV.
Nephrotic Syndrome
1.
2.
3.
4.
Membranous
Causes;
1 ry =70-80%.
2 ry;
- Malignancy; solid, NHL.
- Infection; HBV, HCV, P malari, S, leprosy.
- syst; SLE, MCTD, sickle.
-drugs; gold, penicillamine, captopril.
Patho;
LM& EM Thick BM, supepithelial deposits. IF; granular Ig G, C3
Prognosis;
40% spont remission
30% persistant proteinuria
30% progress to RF. need cytotoxic therapy
TTT
Alternate monthly for 6-12 months;
- pulse steroid then 0.5 mg/kg/d
- chlorambucil or oral cyclophosphamide.
Membranous GN :
PAS
perihilar
Path;
LM; FSGS.
EM; 1rydiffuse efface of foot process.
2 ry patchy efface of foot process.
IF; -ve except for Ig M & C3 trapped in sclerotic lesions
TTT
2ry as any nephrotic, TTT of the cause.
1ry steroid 1mg/kg/d for 3-4 months then
- if complete responsetaper after 1-2 wks over 3 months.
- if partial response (>50%)taper over 6-9 months.
- if little response add cyclosporin & switch to alternate day
then taper over 3 wks.
Hereditary nephropathies
ALPORT'S SYNDROME & Thin GBM
Transmisson;
1) 80%XL -------------------------- Alport, Thin GBM
= mutation in type IV collagen fibrils fragile GBM.
2) 15%AR, --------------------------- homozygous Alport , heterozygous Thin GBM
mutation in type IV collagen fibrils
3) 5% AD.
Clinical picture;
Alport:
Microscopic hematuria; begins at about 5 to 7 years of age.
Nephrotic proteinuria, HTN, ESRD late adolescence.
Extrarenal manifestations;
1- sensorineural deafness, start gradually in childhood, handicap
by 20 years of age.
2- Ocular abnormalities;lenticonus, Dot-and-fleck retinopathy;
not interfere with vision.
3- esophageal leimyomas .
Thin GBM= Benign familial hematuria
represent 25% of patients with microscopic hematuria.
Nail-Patella Syndrome
AD.
Clinical picture; appear at any age.
1) proteinuria to nephrotic syndrome.
2) nail dysplasia. (absent thumb nails)
3) Skeletal manifestations; absent patella, elbow dysplasia.
4) Eye manifestations; Heterochromia of the iris, cataracts.
FABRY'S DISEASE
diabetic nephropathy
Incidence
Microalbuminuria
30-300 mg/24h
= 20-200 Ug/min
= U alb/creat 0.03-0.3.
Progress in
- 80% of type 1 & 20% of type 2 without ttt.
Histopathology
LM;
Thick BM.
Mesangial expansion (diffuse, nodular=Kimmelstiel-Wilson lesion).
Aff & eff arteriolar hyalinosis.
EM;
-fibrin cap (esinophilic focal thickening of a peripheral cap loop)&
- capsular drop (esinophilic focal thickening of bowmans capsule).
IF; psuedolinear deposition of alb & Ig G along BM.
Antihypertensives
1) ACEI;
Acute rise of serum creatinine of up to 30-35%, stabilize after 2
months, may occur in proteinuric patients with serum creatinine
>1.4mg/dl.
greater increase of serum creatinine should raise the possibility of
RAS.
Albuminuria, serum creatinine and K should be checked monthly till 23 months.
2) DHP CCBs (nefedipine- amlodipine):
may increase proteinuria and accerelate the progression of diabetic
nephropathy.
3) NDHP CCBs (deltiazem, verapamil) may reduce proteinuria.
Lupus Nephritis
(WHO) classification & clinical presentation
INormal;-------------------Mild proteinuria
II Mesangial proliferation;---------------------asymptomatic hematuria or proteinuria
III Focal proliferative (FPGN); <50% of all glomeruli----active generalized SLE
------------------------mild-to-moderate renal disease
IV Diffuse proliferative (DPGN);-------Nephritic nephrotic + active generalized SLE
VMembranous;-----------nephrotic syndrome, usually without manifestations of
active SLE.
VI Advanced sclerosis , >90% of glomeruli------------significant renal insufficiency
Lab of lupus nephritis activity; +ve anti DNA,C3, C4 , +ve anti C1q(most
specific), antinucleosome Ab , urine (hematuria, RBCs casts).
Value of renal biopsy; poor correlation between C/P & histopath., associated
pathology e.g. drug induced AIN, TMA.
Characteristic lesions
LM;
Wire-loop lesion = massive subendothelial immune deposits
Hyaline thrombi = large intracapillary immune deposits
Fibrinoid necrosis = intimal immune and fibrin deposits
IF: full-house with IgG, IgA, IgM, C1q, C3, fibrin, and light chains.
EM:
All level dense deposits IImesangial;
III and IV mesangial,subendothelial,
Vsubepithelial
Fingerprint subtructure immune deposits ,
Tubuloreticular inclusions, present also in HIV, most diagnostic.
Therapy
Class I: no specific therapy.
Class II: if proteinuria > 1 g/dprednisone (20-40 mg/d)
for 1-3 months.
Classes III and IV;
Induction; pulse steroid +IV cyclophosphamide or MMF
Maintenance; prednisone 1 mg/kg/d gradual tapering to 5-10
mg/d for 2 years + azathioprine or MMF.
Class V: as 1ry membranous.
Renal affection in rheumatoid arthritis;
- Drug toxicity; NSAIDs AIN+nephrotic.
- 2ry amyloidosis.
Gammopathies
= diseases of globulins
=immunoglobulin overproduction
Monoclonal Gammopathy
Polyclonal Gammopathy
Due to proliferation of many
B cell clones
e.g. CLD, Chr. Inflammation,
infection.
Multiple Myeloma
= CAST NEPHROPATHY
Precipitating factors
1. Volume depletion
2. Hypercalcemia
3. NSAIDs
4. Intravenous contrast
5. Infections
Pathogenesis
A. Increased tubular concentration of light chains enhanced by
decreased urine flow and furosemide.
B. Binding and co-aggregation with Tamm- Horsfall proteintubular
cast in the distal tubule then the proximal tubule
C/P;
Acute renal failure
10% to 15% present with ESRD
> 75% have subnephrotic range proteinuria
1. Mainly Bence-Jones proteinuria
2. Often dipstick negative
V. Treatment
A. Restore intravascular volume
B. Remove offending agents and nephrotoxic drugs
1. Hypercalcemia
i. Volume repletion
ii. Bisphosphonates in refractory cases.
C. Reduce light chain levels
1. Chemotherapy
i. Thalidomide plus dexamethasone,
or
ii. Bortezomib plus dexamethasone
D. Stem cell transplantation +/- kidney transplant is an option in
selected patients.
VI. Management of ESRD
A. Survival on dialysis is significantly decreased in patients with
dysproteinemia who reached ESRD.
1. Median survival was 2 -4 years for LCDD, & AL amyloidosis and 1
year for multiple myeloma.
Slide no 12
AMYLOIDOSIS
TYPES OF AMYLOIDOSIS
1. AL amyloidosis
2. AA amyloidosis
3. Dialysis-related amyloidosis
4. Heritable amyloidoses e.g. heritable neuropathic
and/or cardiomyopathic amyloidosis due to deposition
of fibrils derived from transthyretin (also referred to as
prealbumin).
5. Organ-specific amyloid Amyloid deposition can be
isolated to a single organ, such as the skin, eye, heart,
pancreas, or genitourinary tract, resulting in specific
syndromes.
Renal Amyloidosis
1.
1.
2.
3.
2.
-
Antiphospholipid antibody
Syndrome
APA +ve & previous clinical event long term warfarin, INR=2-3.
APA +ve & pregnancy heparin.
scleroderma
Renal failure in scleroderma;
- renal crises.
- TMA
- Membranous.
Path; as TMA but affect arcuate & interlobular arteries,
onion skin appearance, hypertrophy of JGA.
Marker of Scl renal crises; anti-RNA polymerase III
C/P; diffuse systemic scl + new onset severe HTN or
RPRF.
TTT; ACEI
Prognosis; continue ACEI after dialysis as 50% may
recover over 3-18 months.
Sickle cell;
Glomerular; hematuria , FSGS.
Tubular; DI , RTA , papillary necrosis.
Renal cell carcinoma.
Sarcoidosis; Ca stones, granulomas, TIN.
Sjogren $; Membranous, RTA.
Cryglobulinemia
Type II
Type III
Monoclonal
Mixed
Mono Ig M against poly Ig
G (RF activity)
Mixed
polyclonal
causes
Waldenstrom
MM
HCV
Plasma cell dyscrasia
- Autoimmune; SLE,
hepatobiliary, GN.
- Lymphoproliferative
- Chronic infection
C/P
Gn;
LM: Marked leukocytic infiltration, intraluminal deposits,
vasculitis with fibrinoid necrosis, TI infiltration.
IF; Ig M&G, C3.
Lab; C4, C1q,+ve cryo, RF, HCV Ab.
Poor prognostic factors;
1. Old age.
2. Recurrent purpura.
3. High s creat.
4. High cryo titre; Clinical and histologic activity does not always
correlate directly with detection of circulating cryoglobulins.
5. Low C3
TTT;
- steroids (pulse then 0.5 mg/kg for 6 months) + TTT of HCV.
- If severe; add cyclophosphamide,
- plasmapharesis& Rituximab.
Hypocomplementemic GN;
- Lupus nephritis
- Post infectious.
- MPGN
- Cryoglobulinemia.
HCV associated nephropathy;
1. MPGN +/- cryoglobulin
2. Membranous GN
3. FSGS
4. Prolif, TMA, fibrillary.
Thrombotic thrombocytopenic
purpura (TTP)
Pathogenesis;activity of VWF cleaving protein to < 5%
large VWF platelet adhesion dt;
- Familial ADAMTS13 mutation.
- Acquired Ig e.g. with ticlopedine,peripartum,sepsis,malig.
C/P; pentade;
fever, hemolytic anemia, thrombocytopenia, CNS, mild renal .
TTT; FFP, plasmapharesis,.
NB: platelet transfusion & antiplatelet e.g. aspirin are
contraindicated.
FU by LDH level.
Prognosis; mortality 90% if untreated, 90% survival if ttt.
1.
2.
3.
1.
2.
3.
4.
5.
6.
Tubulointerstitial diseases
1.
2.
3.
4.
Causes;
Drugs; antibiotics, diuretics, NSAIDs.PPI.
Infections e.g.bact, viral as CMV, Hanta V, fungal.
Immune dis; SLE, Sjogren, sarcoid, cryo, acute transplant
rejection.
Idiopathic.
C/P; Fever, rash, arthralgias +/- flank pain, hematuria.
Lab; Serum.., KFTs, & electrolytes.
Urine.....RBCs , WBCs, White cell casts, eosinophiluria,
Eosinophilia, tubular defects, proteinuria<1g.
TTT; stoppage of offending agent high dose steroid for 2-3
wks for drug induced & systemic dis. not for infection.
1.
2.
3.
4.
Causes;
Drugs; analgesics, lithium, heavy metals as lead, calcinurin inhibitors.
Infections e.g. EBV.
Immune dis; SLE, Sjogren, sarcoid, cryo, chronic transplant rejection.
Obstructive uropathy.
Effect of NSAIDS
Vasomotor ARF.
Acute interstitial nephritis + nephrotic S.
Acute papillary necrosis.
Nacl retension.
K in low RAA as DM, ACEI.
CKD; either NSAIDS- induced CKD.
analgesic nephropathy
Mixture; aspirin,
paracetamol, caffeine ( 2-3)
Kg).
age> 60
40-50
less
Diagnosed by non-contrast
CT papillary necrosis &
medullary calcification, small
kidneys, irregular contour.
Papillary necrosis
Vesicoureteric reflux
Not inherited.
Most common cause of ESRD in children.
Child with UTI 30% VUR.
NB;
Most common inherited cause of ESRD ADPKD.
Most common inherited cause of ESRD in
childrennephronophthisis (as medullary cystic dis).
Reflux nephropathy=VUR + CIN.
Grades; I ureter
II ureter & pelvis ( without dilatation).
III pelvic dilatation, preserved forniceal angles.
IV blunting of forniceal angles.
V clubbing of forniceal angles.
Diagnosis;
- early micturating cystography, dynamic renal scan.
- late U/S, DMSA scan.
Screening for VUR in:
: 1st attack of UTI at any age.
: 2nd attack or- 1st with family history,
- abn. Voiding,
- HTN,
- poor growth,
TTT;
Grade I nothing.
Grade II, III till puberty antibiotics TMP-SMX or nitrofurantoin,
cephalexin.
Grade IV, V Long-term antibiotics or surgery.
NB: Surgical correction of VUR in children have failed to show significant
benefit in terms of renal function & progressive scarring. Surgical
correction is reserved for the child who, in a 2- to 4-year period, appears
to be not responding to medical therapy.
Hereditary;
ADPKD.
ARPKD.
Tuberous sclerosis
Von Hippel-Lindau disease (VHL)
Juvenile nephronophthisis and medullary cystic disease.
Acquired renal cysts;
Medullary Sponge Kidney.
acquired cystic disease.
Simple cysts.
Mode of
Inheritance
Renal
Abnormalities
Extra-Renal
Abnormalities
ADPKD
AD
Cortical and
medullary cysts
Nephronophthisis
AR
Small fibrotic
kidneys; medullary
cysts
Retinitis pigmentosa
Medullary cystic
kidney disease
AD
Small fibrotic
kidneys; medullary
cysts
None
Tuberous sclerosis
AD
Renal cysts;
angiomyolipomas;
Von Hippel-Lindau
disease
AD
1.
TTT;
1. ACEI, ARBs
2. If Hge; analgesics, rest, hydration.
3. If infected; bl culture not urine,sutrim, cipro, vanco not ceph nor aminogly.
4. Recently V2 receptor blockersprogression.
5. Sirolimus.
APKD
Tuberous sclerosis
AD, hamartin (tumor suppressor)multiple hamartomas.
Clinical Picture;
CNS epilepsy in 80%, Mental retardation.
SkinFacial adenoma sebaceum, Shagreen patches
(lower back), Ash leaf (Hypomelanotic macules).
Periungual fibromas.
Renal (60%) cysts, Angiomyolipomas.
Retinal hamartoma (50%), is almost always
asymptomatic.
Liver ( 40% ), angiomyolipomas and cysts.
Heart (rhabdomyoma).
Lung (lymphangiomyomatosis; affects females)
Renovascular HTN
Clues;
- abrupt onset, accelerated HTN.
- recurrent flash pulmonary edema.
- Deterioration in renal function with BP reduction
and/or ACE inhibitor therapy.
- Generalized atherosclerosis obliterans.
- asymmetrical kidneys.
Causes;
- RAS (narrowing > 50%)
- vasculitis
- TMA.
114
FMD
Hypertensive Nephrosclerosis
27% of ESRD patients.
risk factors for progression to ESRD include age,
sex, race, smoking, hypercholesterolemia,
duration of hypertension, and preexisting renal
injury.
Kidney biopsies (not needed); arteriolosclerosis,
chronic nephrosclerosis, and interstitial fibrosis
in the absence of immune deposits .
TTT; Treating hypertension <130/80 mmHg if
there is preexisting diabetes or kidney disease,
most patients begin therapy with two drugs,
classically a thiazide diuretic and an ACE
inhibitor.
Atheroembolic disease
Def; separation of cholesterol crystals from atheromatous
plaques to small renal arteries.
Etiology; Vascular disease; classically occurs within days
weeks of manipulation of the aorta or other large vessels as
coronary angio, or in the setting of anticoagulation.
Urinary tracts
Complicated UTI;
- In structural or functional abn e.g. anatomic
abnormality, Instrumentation, Medical condition; as
Pregnant, Diabetic CKD,
transplant,Nosocomial,Childhood UTI, symp.> 7d, Drugs;
antibiotics, immunosup.
- Elderly, men & children.
diagnosis; bact count >105.
TTT; 7 days for lower & 14 days for upper UTI with broader
spectrum Ab covering pseudomonas e.g.
Piperazin/tazobactam, Cefepime, Imipenem, Meronem,.
if recurrentlong term suppressive therapy ie full dose
then dose when culture ve.
Catheter-Associated UTI
Asymptomatic patient
no therapy is indicated. (as relapse is very
common).
In symptomatic patient
antibiotics is based on the Gram's stain of urine
or the antimicrobial sensitivity patterns.
Prophylactic antimicrobial therapy
In case the time of catheterization is clearly
limited (e.g., in gynecologic , vascular surgery,
kidney transplantation).
UTI in Men
In men > 50 years with UTI,
- Intensive therapy for at least 4 to 6 weeks
up to 12 weeks is recommended due to deep
tissue invasion of the prostate & the kidneys
even in the absence of overt signs of
infection at these sites.
Treat Relapse
(1) long-term antimicrobial suppression
(2) surgical removal of the infected prostate.
1.
2.
Etiology of Urolithiasis
Anatomical causes
- ureteropelvic junction (UPJ) obstruction,
- Horseshoe or ectopic kidney
- vesicoureteral reflux,
- calyceal diverticula
- medullary sponge kidney
Metabolic causes
- low urinary volume,
- hypercalcuria (25%40%),
- hyperoxaluria (10%50%),
- hyperuricosuria(8%30%) and
- hypocitraturia (5%30%)
Etiology
Diagnosis
Treatment
Alkali supplements +
Idiopathic hypercalciuria
50%
Hereditary (?)
Normocalcemia, unexplained
hypercalciuria ( > 300
mg / 24 hrs ).
diet; thiazide
1ry hyperPTH
Neoplasia
Unexplained hypercalcemia
Surgery
Distal RTA
Hereditary
Hyperchloremic acidosis,
minimum urine pH >5.5
Alkali replacement
hyperoxaluria
Hypocitraturia
Alkali supplements
%Occurrence
Etiology
Diagnosis
Treatment
Clinical diagnosis
Uric acid stones,
Urine uric acid
>750 mg /d (women),
>800 mg /d (men)
Cystine stones 1%
Hereditary
Struvite stones
5-10%
Infection
Stone type
Antimicrobial agents
Hyperuricosuria
50% Gout
50% Idiopathic
Dehydration
Acetohydroxamic acid
judicious surgery
Dietary modification
Increase fluid intake to maintain urine output of 2-3 l/day:
Decrease intake of animal protein
Restrict salt intake
Normal calcium intake.
Decrease dietary oxalate;
RENAL STONES
Calcium oxalate stones are the commonest kind of stones.
Calcium phosphate stones are the second commonest and
associated with 1ry hyperpara, d RTA, CAI (alkaline urine(.
Uric acid stones (5% of all stones) are associated with high
purine metabolism, chronic diarrhoea, gout.
cystine stones associated with amino aciduria; a disorder of
proximal tubular cells. (COAL cystine, ornithine, arginine,
lysine) .
Proteus splits urea into ammonia, causing alkaline urine
struvite stones (magnesium ammonium phosphate).
Radiopaque stones are: Calcium oxalate, calcium phosphate,
triple phosphate, cystine stones.
Radiolucent stones are: Uric acid, xanthine stones.
Beverage type
risk
Decreased
Alcohol
Decreased
Milk
Decreased
Lemon juice
Decreased
Grapefruit juice
Increased
Cranberry juice
Increased
Carbonated
beverages
Cola
Increased
Increased
Proposed mechanism(s)
Promotors
Oxalate
Sodium
Animal protein
Vitamin C
Dietary calcium
Potassium
Phytate
calcium excretion
Inhibition of calcium oxalate crystal formation
Magnesium
Urinary citrate
Vitamin B6
Hyperoxaluria
Retroperitoneal fibrosis
1.
2.
3.
4.
5.
Prerenal ARF;
- High BUN/CR ratio>20.
- FENa < 1 %
-UNa <10 mmol/L
- high urine osmolarity > 500 mosm/l.
- SG >1.018.
Diagnosis
cause
serum
urine
ttt
Rhabdomyolysis
(Myoglobinuria)
Physical
Metabolic &
elect.
Drugs.
infections
Increased
U/A positive for
myoglobin,
heme but no
CPK,creatinine, RBCs
P, K, uric acid,
high AG MA,
Ca.
BUN/creat<10
Hemolysis:
recent blood
transfusion,
G6PD, PNH,
cold Ab
Fever,
other evidence
of transfusion
reaction
Pink plasma,
Increased LDH
Tumor lysis
recent
chemotherapy
Hyperuricemia,
increased LDH
Urate crystals
urine uric
acid/u creat>1
Fluid therapy
forced alkaline
diuresis with
HCO3,
mannitol in
dextrose
alkalinization
of urine,
allopurinol,
uricase,
fuboxostat
Hepatorenal syndrome
1.
2.
3.
4.
5.
1.
2.
3.
4.
Contrast nephropathy
Non oliguric ATN acute rise of serum creatinine 24-48 hrs
after administration of IV contrast, peak = 3-5 days, baseline =
7-10 days.
Risk factors; DM, CKD, MM, ACEI, NSAIDS, prerenal failure,
high dose.
Pathophysiology; VC & tubular toxicity.
Prevention;
1. Use of low osmolality, non ionic contrast agent e.g. gadopentate
dimeglumine (ultravest).
2. Least dose.
3. IV infusion of NS 1-2 hrs before to 24 hrs after at a rate of 1
ml/kg/hr.
4. Acetylcysteine 600 mg sachet/12 hr 2 days before.
5. +/- theo 2 ds before, nefidipine 10 mg subluigual before.
6. # mannitol, frusemide, dopamine, ANP.
TTT; fluid chart, electrolytes, HD.
NB; Gadolinium in MRInephrogenic systemic fibrosis.
> 90b
6089
3059
1529
< 15
Neuromuscular disturbances
Fatigue, Sleep disorders
Headache, Impaired mentation
Lethargy, Asterixis
Muscular irritability PN,
Myoclonus, Myopathy
Restless legs syndrome
Seizures, Coma
Muscle cramps
Dialysis disequilibrium
Cardiovascular and
pulmonary disturbances
Arterial hypertension CHF
Pericarditis,Hypertrophic or
dilated cardiomyopathy ,
Accelerated atherosclerosis
Hypotension and arrhythmias
Vascular calcification)
Dermatologic disturbances
Pallor, Hyperpigmentation
Pruritus Ecchymoses
Nephrogenic fibrosing
dermopathy ,Uremic frost
Gastrointestinal
disturbances
Anorexia, Nausea and
vomiting, Peptic ulcer
Gastrointestinal bleeding
Idiopathic ascites.
Hematologic and
immunologic disturbances
Anemia
Bleeding diathesis
Increased susceptibility to
infection
Leukopenia
Thromboathenia
Treatment
* Slowing the Progression of CKD
1.
2.
3.
4.
5.
6.
1.
2.
3.
4.
Hypotension.
Muscle cramps.
Anaphylactoid reactions to the dialyzer.
Disequilibrium S.
Peritoneal Dialysis
In peritoneal dialysis, 1.53 L of a dextrosecontaining solution is infused into the peritoneal
cavity and allowed to dwell for a set period of
time, usually 24 h.
As with hemodialysis, toxic materials are
removed through a combination of ultrafiltration
and down a concentration gradient.
The major complications of peritoneal dialysis
are peritonitis, catheter-associated infections,
weight gain and other metabolic disturbances,
and residual uremia.
Anemia of CKD
2.
3.
4.
1.
TTT
1.
1.
2.
1.
2.
Correct Fe deficiency
if ferritin <200 ng/ml & TSAT<20%.
Target ferritin 200-500 ng/ml & TSAT=20- 50%.
For predialysis oral 200mg elemental Fe/d or IV 200mg/1-3
months.
for HDIVI, 100mg for 10 sessions then /wk.
Side effects;
free Fe reaction; N,V,BP, back pain.
Anaphylaxis (Fe dextran due to anti-dextran Ab).
Contraindications;
Active inflammation.
Fe overload.
2) Erythropoietin
1.
2.
3.
4.
Renal Osteodystrophy
A systemic disorder of mineral and bone
metabolism due to CKD manifested by either
one or a combination of the following:
- Abnormalities of calcium, phosphorus, PTH,
or vitamin D metabolism
- Abnormalities in bone turnover,
mineralization, volume, linear growth, or
strength
-Vascular or other soft tissue calcification
Renal Osteodystrophy
A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
- Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism
- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
-Vascular or other soft tissue calcification
Pathogenesis;
1.
2.
3.
4.
Classification;
High turnover disease (2 ry PTH > 300 pg/ml or osteitis fibrosa).
low turnover (adynamic) bone disease ( PTH<150 pg/ml ) due to Ca load= overtreated.
Osteomalacia ( defective mineralization) due to Alm. Toxicity, Vit D, metabolic acidosis, P.
Mixed uremic osteodystrophy; 2 ry PTH + Osteomalacia
PO4
Vit D
Ca
Bone
PTH
1.
2.
1.
2.
3.
4.
5.
6.
C/P;
Bony aches, reccurent pathological fractures.
Soft tissue calcifications; vascular, valvular, skin.
calcifications in atherosclerotic plaques, arteriosclerosis,
calciphylaxis.
Diagnosis;
Intact PTH= full length PTH (1-84)(active) + PTH
fragment (7-84)( inactive accumulate in RF).
Bone specific ALK P (osteoblastic act).
Bone biopsy.
X rays.
DEXA.
Desferoxamine test for Alm tox.
C
7
PTH
84
TTT
1.
2.
3.
Slide no 9
Transplantation
1.
2.
3.
4.
Tissue Typing;
ABO(O) blood groups
human leukocyte antigen (HLA) class I
(A, B, C) or class II (DR) antigens
Punnel of reactive antibodies (PRA)
cross-match of recipient serum with
donor T lymphocytes
Hyperacute
Accelerated
acute
Acute
Chronic
immediate
5 days
5 d-4 m
> 4m
Mechanism Humoral
cellular &
humoral
cellular
cellular &
humoral
Effector
memory T
cells
T cytotoxic
T helper & B
lymphocytes
Interstitial
tissue
mononuclear
& neutrophyl
infiltration &
vasculitis
Interstitial
tissue
mononuclear
infiltration
Chronic
interstitial
nephritis &
fibrosis
onset
preformed Ab
Pathology Intravascular
thrombosis
Immunosuppressive Treatment
1. Induction therapy with Antibodies to Lymphocytes;
Depleting Ab e.g.
- ATGAM, OKT3
- Thymoglobulin is the most common
agent currently in use.
- Alemtuzumab
non- Depleting Ab e.g.
- anti CD25 (IL2 receptors); Basiliximab &
Daclizumab.
- Belatacept (costimulatory pathway blockade)
2. Maintenance Immunosuppressive Drugs
Agent
Mechanisms
Side Effects
Glucocorticoids
Cyclosporine CsA
Tacrolimus (FK506)
Azathioprine
Mycophenolate
mofetil (MMF)
Diarrhea/cramps; dose-related
liver and marrow suppression is
uncommon
Sirolimus
Hyperlipidemia, thrombocytopenia
BK virus
BK virus nephropathy & ureteral stenosis.
Urothelial carcinoma,vasculopathy.
Biopsy; patchy interstitial infiltration, IF; Ab to
simian v. 40.
Urine cytology +ve for decoy cells(tubular cells
appear malignant due to viral inclusions.
PCR.
TTT; reduce IS, leflunamide, cidofovir.
Malignancy
The incidence of tumors in patients on
immunosuppressive therapy is 56%, or approximately
100 times greater than that in the general population of
the same age range.
The most common lesions are cancer of the skin and lips
and carcinoma in situ of the cervix, as well as
lymphomas such as non-Hodgkin's lymphoma.
The risks are increased in proportion to the total
immunosuppressive load administered and time elapsed
since transplantation.
Surveillance for skin and cervical cancers is necessary.
Slide no 2
This skin lesion
appeared 2 months
after a successful
renal transplant
What is the most
likely diagnosis
recurrence
15%
10%
50%
50%
graft loss
50%
50%
15%
anti-GBM
TTP
HELLP
Acute fatty
liver
HUS
Cortical
necosis
timing
3rd trimester
3rd trimester
(more common)
postpartum
postpartum
Hge e.g.
abruptio
placentae
C/p
Fever
neuro
-Mild renal
failure
-Proteinuria
-HTN
-Severe
renal failure
- Poor renal
prognosis
Oliguria
Hematuria
Flank pain
Lab
-plat, Hb
-uncong. bilirubin
-shistocytes
-liver enz
-uric acid
-Hypocalcuria
-PT, PTT,
plat
-liver enz
-PT, PTT, plat
-fibrinogen
-congugated bil
- hypoglycemia
ttt
plasmapharesis
termination
termination
Hypo or
hyper echoic
areas in US
Supportive
dialysis
dialysis