Nejm 1998;339:894; 1998;338:1202; 1994;330:61

Cause:

Primary types:

• Membranous GN (Membranous Glomerulonephritis); the cause in 7% of children with nephrotic syndrome, and in 40% of adults
• Minimal change GN (Minimal Change ("Lipoid") Nephritis); the cause in 76% of children and 20% of adults
• Chronic proliferative GN (40%); in 4% of children and 7% of adults
• Focal, segmental GN; in 8% of children and 15% of adults
• Other: in 5% of children and in 18% of adults

Secondary types:

• SLE and other collagen vascular diseases
• Amyloid (esp in rheumatoid arthritis; multiple myeloma; familial Mediterranean fever; chronic infections like SBE, hepatitis B, and HIV)
• Bee stings and snake venom
• Diabetic Kimmelstiel-Wilson disease
• Heavy metal drug rx, eg, gold
• Chronic iv heroin use (Nejm 1974;290:19; Ann IM 1974;80:488)
• Cancer, eg, lung, probably by paraneoplastic antibody–antigen complexes (Nejm 1993;328:1621), colon, prostate, breast

Pathophys:Protein losses in urine lead to all si’s and sx’s and lab abnormalities. Caused by 2 types of pathologic processes: generalized uniform basement membrane thickening or damage as seen in membranous GN, and minimal lesion types caused by an elutable small protein deposited on the glomeruli (Nejm 1994;330:7); and spotty deposition of immune complexes as seen in poststreptococcal nephritis, SBE, SLE, and serum sickness

Elevated lipids; LDL is increased by slowed metabolism and an increase in apoprotein B production (Nejm 1990;323:579)

Sx:Edema, periorbital in the morning and pedal in the afternoon

Si:Edema, anasarca

Infections, if IgG loss; renal vein thrombosis (Ann IM 1976;85:310); hypercoagulable states in 50% lead to pulmonary emboli, etc; malabsorption of food and meds due to bowel wall edema; accelerated ASHD

r/o myeloma and primary renal (AL) amyloidosis w urinary immunoelectrophoresis

Lab:

Chem:LDL cholesterol is increased (Ann IM 1993;119:263); hypoalbuminemia

Path:Renal biopsy usually shows etiology, foot process fusion by electron microscopy in minimal lesion GN; “wire loops” by light microscopy in membranous GN; increased mesangial cells without polys in proliferative GN

Serol:Serum protein electrophoresis (SPEP) shows decreased IgG in membranous GN type (“big holes” let IgG leak out); decreased complement; increased ₂- and -lipoprotein

Urine:24-h protein >3-3.5 gm; “oval fat bodies” (fat-laden tubular cells in sediment). Protein/creatinine ratio on random urine as good or better than 24-h urine; <0.2 is normal, 3.5 is nephrotic

Rx:

Diuretics and severe Na restriction

Captopril and other ACE inhibitors improve lipids (Ann IM 1993;118:246) and lower protein excretion

Antihyperlipidemia rx

Anticoagulation w warfarin or at least ASA

Specific rx to etiologic diagnosis