NP20 Nephrology

Parenchymal Kidney Diseases

Nephrotic

Intermediate

Essential Med Notes 2015

Nephritic
Hematuria, ! GFR

Proteinuria
FSGS
Membranous glomerulopathy
Minimal change

Membranoproliferative GN
Focal proliferative GN
IgA nephropathy
Idiopathic membranoproliferative GN
HBV, HCV
SLE
Cryoglobulinemia

Diffuse proliferative GN
Crescentic GN

Figure 11. Spectrum of glomerular pathology

PROTEINURIA
hallmark of nephrotic syndromes
24 h urine protein: gold standard to assess degree of proteinuria
urine ACR: used to screen for diabetic nephropathy
microalbuminuria
defined as ACR 25 mg/g (female) or ACR 18 mg/g (male)
marker of vascular endothelial function
an important prognostic marker for kidney disease in DM and HTN (see Diabetes, NP28)
an elevated ACR 18 or 25 mg/g is the earliest sign of diabetic nephropathy
composition of normal total urine protein
upper limit of normal daily excretion of total protein is 150 mg/d
upper limit of normal daily excretion of albumin is 30 mg/d
the other normally excreted proteins are either filtered low molecular weight proteins (such
as immunoglobulin light chains or -2 microglobulin) or proteins secreted by the tubular
epithelial cells (e.g. Tamm-Horsfall mucoprotein)
Proteinuria

Pathologic

Physiologic
Orthostatic
Absence of proteinuria overnight
Usually resolves spontaneously
Transient (exercise, fever, CHF)

Tubulointerstitial
(impaired resorption)
<2 g/d
e.g. Fanconis syndrome

Glomerular
(loss of large proteins [albumin])

Primary
Minimal change GN
Membranous GN
FSGS
Membranoproliferative GN
Poststreptococcal GN
IgA nephropathy

Overflow
(overproduction of low molecular
weight proteins)
e.g. multiple myeloma, amyloidosis,
Waldenstroms macroglobulinemia

Secondary
Systemic disease
SLE, DM, vasculitis
Infectious disease
HIV, hepatitis B and C, bacterial endocarditis
Hereditary/metabolic
Alports, Fabrys, sickle cell, PCKD
Medications
NSAIDs, gold, heavy metals
Cancer
Lymphoma, solid tumor
Others
Cryoglobulinemia, hypertensive nephrosclerosis

Figure 12. Classification of proteinuria

Table 9. Daily Excretion of Protein
Daily Excretion

Meaning

<150 mg total protein (and <30 mg albumin)

Normal

30-300 mg albumin

Microalbuminuria

>3500 mg total protein/1.73m2 BSA

Nephrotic range proteinuria

Variable amount of proteinuria

Can be seen with glomerular disease; e.g. mild glomerular disease can lead to
a mild degree of proteinuria, proliferative lesions may also be associated with
some degree of proteinuria

Up to 2,000 mg per d

Possible tubular disease because of failure to reabsorb filtered proteins

Pathologic Proteinuria
Tubulointerstitial
Normally low molecular weight
proteins (<60 kDa) pass through
glomerular filtration barrier and are
reabsorbed in proximal tubule
Proximal tubule dysfunction causes
impaired reabsorption and increased
excretion of low molecular weight
proteins
Albumin (>60 kDa) is not affected;
thus, edema is partly secondary to
salt and water retention
Glomerular
Normally, the filtration barrier is
selectively permeable to size
(<60 kDa) and charge (repels
negative particles); thus, albumin
is filtered to a very limited extent
through a normal glomerulus
Damage to any component of
the glomerular filtration barrier
results in loss of albumin and other
high molecular weight proteins;
thus, edema is secondary to
hypoalbuminemia (low oncotic
pressure), but also due to enhanced
renal tubular reabsorption of filtered
sodium and water (possibly due to
filtered proteins stimulating the action
of cortical collecting duct epithelial
sodium channel)
Overflow
Increased production of low molecular
weight proteins which exceeds the
reabsorptive capacity of the proximal
tubule
Plasma cell dyscrasias: produce
light chain Ig (multiple myeloma,
Waldenstroms macroglobulinemia,
monoclonal gammopathy of
undetermined significance)