Five patients present to the nephrology service with varying degrees of acute kidney injur… — USMLE Step 3

Five patients present to the nephrology service with varying degrees of acute kidney injury, edema, and hematuria. Normal complement reference ranges are C3 $90-180\text{ mg/dL}$ and C4 $10-40\text{ mg/dL}$ . Based on the distinct serologic and urinalysis profiles provided, pair each laboratory pattern with its correct clinical diagnosis.

Urinalysis: dysmorphic RBCs, RBC casts. Serum: C3 $45\text{ mg/dL}$ , C4 $8\text{ mg/dL}$ , positive anti-dsDNA.Systemic lupus erythematosus nephritis
Urinalysis: dysmorphic RBCs. Serum: C3 $105\text{ mg/dL}$ , C4 $4\text{ mg/dL}$ , positive rheumatoid factor, positive cryoglobulins.Mixed cryoglobulinemic glomerulonephritis
Urinalysis: dysmorphic RBCs. Serum: C3 $35\text{ mg/dL}$ , C4 $22\text{ mg/dL}$ , positive anti-streptolysin O (ASO).Poststreptococcal glomerulonephritis
Urinalysis: $4+$ protein, oval fat bodies. Serum: C3 $115\text{ mg/dL}$ , C4 $25\text{ mg/dL}$ , positive anti-PLA2R antibodies.Primary membranous nephropathy
Urinalysis: dysmorphic RBCs, RBC casts. Serum: C3 $120\text{ mg/dL}$ , C4 $24\text{ mg/dL}$ , positive PR3-ANCA.Granulomatosis with polyangiitis

Cevap

Properly pairing the laboratory profiles requires analyzing the complement pathways. Low C3 and C4 indicates classical pathway activation (Lupus nephritis). Markedly low C4 with normal C3 is unique to mixed cryoglobulinemia. Isolated low C3 indicates alternative pathway activation (Poststreptococcal GN). Normal complements with nephrotic sediment points to primary membranous nephropathy, while normal complements with nephritic sediment and PR3-ANCA indicates granulomatosis with polyangiitis.

Each glomerulopathy has a distinct serologic signature. Lupus nephritis activates the classical pathway (low C3 and C4) and features ANA/anti-dsDNA. Cryoglobulinemia prominently lowers C4 (often normal C3) due to classical pathway activation by immune complexes with rheumatoid factor activity. Poststreptococcal glomerulonephritis activates the alternative pathway, lowering only C3, with evidence of prior strep infection (ASO). Primary membranous nephropathy is a non-inflammatory nephrotic syndrome with normal complements and anti-PLA2R antibodies. Granulomatosis with polyangiitis is a pauci-immune vasculitis causing nephritic syndrome with normal complements and positive PR3-ANCA.

Glomerulopathy	C3 Level	C4 Level	Key Autoantibody
Systemic Lupus Erythematosus Nephritis	Low	Low	Anti-dsDNA, ANA
Mixed Cryoglobulinemia	Normal	Low	Rheumatoid factor
Poststreptococcal GN	Low	Normal	ASO, Anti-DNase B
Granulomatosis with polyangiitis	Normal	Normal	PR3-ANCA
Primary Membranous Nephropathy	Normal	Normal	Anti-PLA2R

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Evaluate the complement levels for each profile.

Patient 1 has low C3/C4; Patient 2 has normal C3/low C4; Patient 3 has low C3/normal C4; Patients 4 and 5 have normal C3/C4.

Complement patterns categorize the mechanism of glomerulonephritis (classical vs. alternative vs. pauci-immune).

Analyze the urinalysis for nephritic versus nephrotic features.

Patients 1, 2, 3, and 5 have dysmorphic RBCs indicating nephritic syndrome. Patient 4 has heavy protein and oval fat bodies indicating nephrotic syndrome.

This broadens the diagnostic categories before confirming with specific autoantibodies.

Correlate specific autoantibodies with the clinical picture.

Anti-dsDNA points to lupus, PR3-ANCA to granulomatosis with polyangiitis, ASO to poststreptococcal infection, and anti-PLA2R to primary membranous nephropathy.

Specific serologies definitively establish the diagnosis when combined with complement and urinalysis data.

Anahtar Kavram

Glomerulonephritis Serologic and Complement Interpretation

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