STEPTRACKERRENAL | PATHOLOGY + IMMUNOLOGY + ENDOCRINE | HIGH-YIELD REVIEW

Nephrotic Syndrome II — MPGN, Diabetes, Amyloid & Lupus

Glomerular diseases that deposit something in the glomerulus — immune complexes, glycated matrix, amyloid fibrils — and the lupus classes.

FOCUS ON
Diabetic nephropathy: efferent arteriole hyalinosis → hyperfiltration → GBM thickening, mesangial expansion, Kimmelstiel-Wilson nodules; ACE inhibitors/ARBs and SGLT2 inhibitors protect. Amyloid: Congo red, apple-green birefringence. MPGN: tram-track GBM, low C3, HBV/HCV. Lupus: class IV (nephritic, wire loops) vs class V (nephrotic, membranous).
DISEASE
MECHANISM
FINDINGS
CLUE
MPGN (immune complex)
Subendothelial immune complexes → mesangial cells grow into the capillary wall and lay down new GBM
"Tram-track" double-contoured GBM; nephrotic or nephritic; ↓ C3
HBV, HCV (cryoglobulinemia), SLE, chronic infection
C3 glomerulopathy / dense deposit disease
C3 nephritic factor (autoantibody) stabilizes C3 convertase → persistent complement activation
Dense intramembranous deposits; persistently low C3
Partial lipodystrophy
Diabetic nephropathy — mechanism
Nonenzymatic glycation of GBM and arteriolar walls; efferent > afferent hyalinosis → ↑ glomerular pressure
Early hyperfiltration → microalbuminuria → overt proteinuria → CKD
Most common cause of ESRD
Diabetic nephropathy — pathology
Matrix accumulates
GBM thickening, diffuse mesangial expansion, nodular sclerosis (Kimmelstiel-Wilson), hyaline arteriolosclerosis
Pink PAS⁺ round mesangial nodules
Diabetic nephropathy — management
Lower intraglomerular pressure
ACE inhibitor / ARB (dilate efferent), SGLT2 inhibitor (restores tubuloglomerular feedback → afferent constriction), glycemic and BP control
Screen yearly for albuminuria
AL amyloidosis
Misfolded immunoglobulin light chains (plasma cell dyscrasia, myeloma)
Nephrotic syndrome, restrictive cardiomyopathy, macroglossia, neuropathy, periorbital purpura
Kidney is the organ most often involved
AA amyloidosis
Serum amyloid A from chronic inflammation
RA, IBD, TB, bronchiectasis, osteomyelitis, familial Mediterranean fever
Treat the inflammation
Amyloid — pathology
β-pleated sheet fibrils in mesangium and vessels
Amorphous pink deposits; Congo red → apple-green birefringence under polarized light
Kidneys often normal or enlarged
Lupus nephritis — class IV
Diffuse subendothelial immune complexes (> 50% of glomeruli)
Wire-loop capillaries; nephritic ± nephrotic; ↓ C3/C4; full-house IF
Most common and most severe class
Lupus nephritis — class V
Subepithelial immune complexes
Membranous pattern → nephrotic syndrome
Treat with immunosuppression

Mechanism — diabetic kidney injury

Hyperglycemia
→
Efferent hyalinosis+ ↑ Na⁺ reabsorption (SGLT2)
→
↑ Intraglomerular pressureHyperfiltration
→
Mesangial expansion, thick GBM
→
Albuminuria → CKD

ACE inhibitors dilate the efferent arteriole; SGLT2 inhibitors deliver more Na⁺ to the macula densa so the afferent constricts — both lower glomerular pressure.

Complement levels in glomerular disease

LOW C3
NORMAL C3
Post-streptococcal GN
IgA nephropathy / IgA vasculitis
MPGN, C3 glomerulopathy
Anti-GBM disease
Lupus nephritis (low C4 too)
Pauci-immune (ANCA) GN
Cryoglobulinemia (low C4)
Minimal change, FSGS, membranous
Endocarditis, shunt nephritis
Diabetic nephropathy, amyloid

How it's tested

COMMON CONFUSIONKimmelstiel-Wilson nodules (diabetes) and amyloid both expand the mesangium. Amyloid is Congo red ⁺ with apple-green birefringence; diabetic nodules are PAS ⁺ and Congo red negative.
THE TRAPPersistently low C3 more than 8 weeks after a "post-strep GN" means it wasn't post-strep — think MPGN or C3 glomerulopathy.
YOUR APPROACHUnderlying disease (DM, myeloma, chronic inflammation, HCV, SLE) → deposit location (subendothelial, subepithelial, mesangial) → complement → special stain.

If you see… think…

Long-standing diabetic, microalbuminuria → early diabetic nephropathy — start ACEi/ARB
Round PAS⁺ mesangial nodules → Kimmelstiel-Wilson (diabetic)
Arteriole hyalinosis affecting efferent more than afferent → diabetes
Tram-track GBM + HCV + low complement → MPGN with cryoglobulinemia
Low C3 + C3 nephritic factor + lipodystrophy → dense deposit disease
Myeloma with nephrotic syndrome and macroglossia → AL amyloidosis
RA for 20 years, now nephrotic → AA amyloidosis
Apple-green birefringence with Congo red → amyloid
SLE, hematuria, RBC casts, wire loops → lupus class IV (diffuse proliferative)
SLE with heavy proteinuria and subepithelial deposits → lupus class V