Glomerulonephritis: A High-Yield USMLE Review

Glomerulonephritis (GN) refers to inflammatory injury of the glomerular filtration barrier that produces a nephritic picture—hematuria with dysmorphic RBCs and RBC casts, often with proteinuria and hypertension. It accounts for roughly 10% of chronic kidney disease in the United States and encompasses several distinct entities (IgA nephropathy, post-streptococcal GN, anti-GBM/Goodpasture disease, lupus nephritis) that are heavily tested through their distinguishing serologies and timing clues.

Presentation

• Hematuria, which may be gross or microscopic; glomerular origin is signaled by dysmorphic RBCs and RBC casts
• Proteinuria (glomerular type, albumin-predominant) from damage to the filtration barrier
• Hypertension
• Slowly progressive chronic kidney disease, or rapidly progressive renal failure in crescentic/aggressive forms
• Entity-specific clues: episodic gross hematuria during or within days of a URI (synpharyngitic) in IgA nephropathy; hemoptysis plus GN in Goodpasture syndrome

Diagnosis

• Urinalysis with microscopy: dysmorphic RBCs and RBC casts confirm glomerular bleeding; concurrent proteinuria supports GN
• Complement levels and serologies to narrow the cause: C3/C4, ANA, ANCA, anti-GBM, ASO, hepatitis B/C (e.g., low C3 favors PSGN, normal C3 favors IgA nephropathy; low C3 and C4 in lupus)
• Kidney biopsy—the definitive test—with light microscopy, immunofluorescence, and electron microscopy to guide treatment (e.g., mesangial IgA deposits diagnostic of IgA nephropathy; linear IgG along the GBM in anti-GBM disease)

Management

• ACE inhibitor or ARB as first-line therapy to control proteinuria and slow progression in proteinuric disease
• Immunosuppression tailored to disease: steroids for crescentic/rapidly progressive IgA nephropathy; plasmapheresis with high-dose steroids and cyclophosphamide for anti-GBM/Goodpasture disease treated early before irreversible damage
• Refer to nephrology for active sediment suggesting GN, heavy proteinuria, or declining eGFR

High-yield

• IgA nephropathy is the most common glomerulonephritis worldwide; look for synpharyngitic gross hematuria with normal C3
• Timing distinguishes look-alikes: IgA nephropathy hematuria occurs DURING/within days of a URI, whereas PSGN follows infection by 1–3 weeks with LOW C3
• Goodpasture syndrome = hemoptysis + GN from anti–type IV collagen antibodies with linear IgG on immunofluorescence; treat with plasmapheresis
• RBC casts and dysmorphic RBCs are the hallmark of glomerular (nephritic) bleeding, in contrast to muddy brown casts (ATN) or WBC casts (AIN)
• Lupus nephritis features anti-dsDNA immune complexes (wire-loop subendothelial deposits) with low C3 AND low C4

Pitfalls

• Confusing IgA nephropathy with PSGN—use timing (synpharyngitic vs. 1–3 week latency) and complement (normal vs. low C3)
• Missing the glomerular origin of hematuria: a positive dipstick can reflect myoglobin or hemoglobin, so confirm true RBCs and look for dysmorphic cells/RBC casts before labeling it GN
• Delaying treatment in anti-GBM disease—dialysis-dependent patients rarely recover renal function, so treat early
• Reflexively starting prednisone for 'presumed GN' when proteinuric CKD without active sediment simply needs an ACE inhibitor/ARB first