Glomerulonephritis

Two syndromes, one filter

A glomerulus filters plasma through three sheets: fenestrated endothelium (lets small things through, holds back cells), the glomerular basement membrane (size and charge barrier), and podocyte foot processes whose slit diaphragms (nephrin, podocin) are the final selectivity gate. Two ways to break it. Inflammation that tears holes — endothelial and mesangial proliferation, crescent formation — lets cells through. That's nephritic: hematuria, dysmorphic RBCs, RBC casts in tubules, mild-to-moderate proteinuria, falling GFR. Damage that specifically wrecks the podocyte/slit-diaphragm gate lets albumin pour through. That's nephrotic: proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia. The biopsy distinguishes which structural lesion is responsible.

Nephritic causes — six to know

• Post-streptococcal GN. Group A Strep pharyngitis (1–3 weeks) or impetigo (3–6 weeks) → subepithelial immune complex deposits ("humps" on EM), low C3, ASO and anti-DNase B positive. Children recover; adults often progress.
• IgA nephropathy. The most common primary GN worldwide. Synpharyngitic hematuria (red urine within days of a URI), mesangial IgA on IF. 30–40% to ESRD over decades.
• Lupus nephritis. SLE in 30–50% of patients. ISN/RPS classes I–VI on biopsy guide therapy. ANA, anti-dsDNA, low C3 and C4. "Full house" immunofluorescence (IgG, IgA, IgM, C3, C1q).
• ANCA-associated vasculitis. Pauci-immune (no immune deposits on IF). c-ANCA / anti-PR3 (GPA), p-ANCA / anti-MPO (MPA, EGPA). Sinus disease, lung nodules or hemorrhage, hematuria.
• Anti-GBM disease (Goodpasture). Anti-α3-IV collagen → linear IgG along GBM. RPGN with pulmonary hemorrhage. Days from diagnosis to dialysis if untreated.
• Membranoproliferative GN. Hepatitis C with cryoglobulinemia, monoclonal gammopathies, complement dysregulation (C3 glomerulopathy). Can be nephritic, nephrotic, or both.

Nephrotic causes — five to know

• Minimal change disease. Most common in children. Light microscopy normal; EM shows diffuse podocyte foot process effacement. Steroids work fast — most are nephrotic-resolved at 8 weeks.
• FSGS. Most common nephrotic in Black adults. Primary (idiopathic podocytopathy, often APOL1 variants) vs secondary (HIV, heroin, obesity, reflux, sickle cell). Steroid-responsive in primary; treat the cause in secondary.
• Membranous nephropathy. Anti-PLA2R antibody positive in ~70% of primary. Secondary causes: solid tumors, hepatitis B, lupus, NSAIDs. Treatment: rituximab or modified Ponticelli (steroids + alkylator).
• Diabetic nephropathy. The biggest single cause of ESRD. Kimmelstiel-Wilson nodules, GBM thickening. Treat with RAASi + SGLT2i + glycemic control + BP control.
• Amyloid nephropathy. AL (light chain) or AA (chronic inflammation). Congo red apple-green birefringence on biopsy. Serum-free light chains, SPEP, UPEP.

Worked clinical example — the post-URI teenager

A 14-year-old presents with cola-colored urine and periorbital puffiness 12 days after a sore throat that "got better on its own." BP 152/96. Labs: creatinine 1.4 mg/dL (baseline 0.7), urinalysis 3+ blood with dysmorphic RBCs and RBC casts, 1+ protein (UPCR 1.2 g/g — sub-nephrotic), C3 28 (low), C4 normal, ASO 1:680 (elevated). The story is post-streptococcal GN: classic timing, classic urine, classic low C3 with normal C4 (alternative pathway activation). Plan: sodium restriction, furosemide for volume and BP, amlodipine if BP >target, follow C3 (should normalize in 6–8 weeks). No steroids, no biopsy unless atypical course. Six months later: BP and creatinine normal; trace persistent microscopic hematuria fine. Adult presentations with this story carry worse prognosis — more often progress to CKD.

Rapidly progressive GN — the emergency

Doubling of creatinine over weeks. Crescents on >50% of glomeruli. Three immunofluorescence patterns split the differential and pick the treatment:

• Linear IgG = anti-GBM disease. Plasmapheresis daily until anti-GBM negative, plus cyclophosphamide and pulse steroids.
• Granular IgG/C3 = immune complex (lupus, post-infectious, IgA, cryoglobulinemic). Treat the underlying disease — cyclophosphamide or MMF + steroids in lupus class III/IV/V, rituximab.
• Pauci-immune = ANCA-associated vasculitis. Induction with rituximab or cyclophosphamide + pulse methylprednisolone; plasmapheresis (PEXIVAS) for severe presentations (Cr >5.7 or pulmonary hemorrhage).

Time matters: each day of delay loses nephrons that don't return. Biopsy and serologies should be in motion within 24 hours of suspicion.

Nephritic vs nephrotic — side by side

Comparing nephritic and nephrotic syndromes

Feature	Nephritic	Nephrotic
Mechanism	Inflammatory breach of filter	Podocyte / slit-diaphragm injury
Proteinuria	<3.5 g/day (sub-nephrotic)	>3.5 g/day (massive)
Hematuria	Yes, with RBC casts	Rare, microscopic if any
Edema	Mild (Na retention)	Marked (low oncotic)
Blood pressure	Hypertension	Often normal
Serum albumin	Preserved or mildly low	<3 g/dL
Lipid profile	Normal	Hypercholesterolemia
Thrombosis risk	Low	High (loses antithrombin III)
Prototype	Post-strep GN, IgA, anti-GBM	Minimal change, membranous, FSGS

Common misconceptions

• "All hematuria = stone or cancer." Dysmorphic RBCs and RBC casts argue glomerular. A urinalysis read with microscopy answers this in 5 minutes.
• "Steroids first, biopsy later." RPGN demands urgent biopsy because treatment differs sharply by immunofluorescence pattern.
• "Children with post-strep GN need biopsy." Classic presentation with ASO+ and low C3 in a child doesn't — recovery is the rule. Biopsy if atypical, persistent C3 low >8 weeks, or no improvement.
• "Nephrotic = give albumin." Infused albumin redistributes into urine within hours. Treat the cause and use loop diuretic if edema is symptomatic.
• "Diabetic kidney disease doesn't need biopsy." True for classic long-duration diabetic with retinopathy and slowly rising creatinine. Atypical features (no retinopathy, rapid decline, active sediment) demand biopsy to find a second diagnosis.