Nephritic Syndromes
A board-focused walk through nephritic syndromes — inflammatory glomerular injury presenting with hematuria/RBC casts, hypertension, and azotemia — organized around the two exam discriminators (complement level and disease tempo) with classic buzzwords, RPGN emergencies, and next-best-step management.
What nephritic syndrome is
Nephritic syndrome is the clinical face of glomerular inflammation: immune-mediated injury to the glomerular capillary wall (endothelium + GBM) lets red cells and protein leak, while the inflamed, hypercellular tuft loses filtration surface.
The result is the nephritic picture plus renal impairment:
- Hematuria — smoky/cola/tea-colored urine with dysmorphic RBCs (acanthocytes) and RBC casts (proof the bleeding is glomerular, not urologic)
- Hypertension and edema (periorbital), from Na⁺/water retention
- Azotemia / oliguria — rising BUN and creatinine as GFR falls
Proteinuria is present but sub-nephrotic (<3.5 g/day) — the key split from nephrotic syndrome, where the podocyte barrier fails and >3.5 g/day is lost with little inflammation. A few entities (diffuse proliferative lupus, MPGN) straddle both. On boards, once you recognize nephritis, two questions crack most vignettes: Is serum complement low or normal? and How fast is renal function falling?
- RBC casts + dysmorphic RBCs (acanthocytes) = glomerular bleeding → nephritic until proven otherwise.
- Branch 1 — serum complement:
- Low C3: PSGN, MPGN, lupus nephritis (↓C3 and ↓C4), cryoglobulinemia, endocarditis-associated GN.
- Normal complement: IgA nephropathy/HSP, anti-GBM, ANCA (pauci-immune) vasculitis, Alport.
- Branch 2 — tempo: creatinine climbing over days–weeks = RPGN → crescents on biopsy → renal emergency.
- Timing of hematuria after infection separates the two commonest:
- 1–3 weeks after strep pharyngitis → PSGN.
- Concurrent with a URI (synpharyngitic, "same-day") → IgA nephropathy.
- Send early: C3/C4, ASO/anti-DNase B, ANA/anti-dsDNA, ANCA, anti-GBM, plus urine microscopy.
Major nephritic diseases at a glance
| Disease | Classic clue | C3/C4 | IF / EM buzzword |
|---|---|---|---|
| PSGN | Cola urine 1–3 wk after strep pharyngitis (or 3–6 wk post-impetigo); child | ↓C3 | Granular "starry-sky"/lumpy-bumpy IgG+C3; subepithelial humps (EM) |
| IgA nephropathy (Berger) | Recurrent gross hematuria with a URI/GI infection; ± HSP purpura | Normal | Mesangial IgA deposits |
| Anti-GBM (Goodpasture) | Hematuria + hemoptysis, young man | Normal | Linear IgG along GBM; crescents |
| ANCA (pauci-immune) | RPGN ± sinus/lung (GPA), asthma+eosinophils (EGPA) | Normal | Pauci-immune (scant deposits); crescents |
| Lupus (class IV, DPGN) | SLE, young woman | ↓C3 & ↓C4 | "Full-house" IF; wire-loop subendothelial deposits |
| MPGN | Hepatitis C / cryoglobulinemia | ↓C3 | "Tram-track" GBM double contour |
| Alport | Hematuria + sensorineural deafness + eye findings | Normal | "Basket-weave" GBM splitting (EM) |
Vignette: An 8-year-old boy develops cola-colored urine, puffy eyelids, and BP 140/95 two weeks after a sore throat. Labs: ↑creatinine, ↓C3, ↑ASO titer; UA shows RBC casts and 1+ protein.
- Diagnosis: Post-streptococcal glomerulonephritis (PSGN) — immune-complex GN; EM would show subepithelial humps.
- Next best step: Supportive care — sodium/water restriction, loop diuretic, BP control. C3 normalizes in 6–8 weeks; children have an excellent prognosis (biopsy only if the course is atypical, e.g., persistent low C3 >8 wk).
Contrast trap: If instead the hematuria appeared during the URI (no 1–2-week lag) with normal complement, the answer is IgA nephropathy, not PSGN.
- Definition: nephritic syndrome + GFR falling over days–weeks; light microscopy shows crescents (macrophages, fibrin, and proliferating parietal cells filling Bowman space).
- Three patterns by immunofluorescence:
- Linear → anti-GBM disease (Goodpasture when lung + kidney); antibody vs type IV collagen α3.
- Granular ("lumpy-bumpy") → immune-complex GN (PSGN, lupus, IgA/HSP).
- Pauci-immune (scant/negative) → ANCA vasculitis: c-ANCA/PR3 → GPA; p-ANCA/MPO → MPA (EGPA is the third ANCA-associated vasculitis).
- Next best step: urgent renal biopsy + serologies (anti-GBM, ANCA, ANA/dsDNA, C3/C4). In fulminant disease, do not delay empiric high-dose steroids while awaiting results — every day of active crescents is nephrons lost.
Vignette: A 24-year-old man has hemoptysis and dark urine; creatinine rose from 1.0 to 3.2 mg/dL over 10 days. Biopsy IF shows linear IgG along the GBM; serum anti-GBM antibodies are positive.
- Diagnosis: Anti-GBM (Goodpasture) disease — antibodies against the α3 chain of type IV collagen shared by alveolar and glomerular basement membrane.
- Next best step: Plasmapheresis (removes circulating antibody) plus high-dose corticosteroids + cyclophosphamide.
- Board pearl: smoking / hydrocarbon exposure unmasks the alveolar hemorrhage. Linear IF = anti-GBM is the single most testable image cue here.
- PSGN: supportive only — Na⁺/water restriction, loop diuretic, antihypertensives; treat any residual strep. Excellent recovery in children.
- IgA nephropathy: ACEi/ARB for proteinuria + BP; add corticosteroids if progressive despite optimized supportive care.
- Anti-GBM: plasmapheresis + steroids + cyclophosphamide, urgently.
- ANCA vasculitis: induction with steroids + rituximab or cyclophosphamide; consider plasmapheresis for severe renal failure or pulmonary hemorrhage.
- Lupus nephritis (class III/IV): corticosteroids + mycophenolate (MMF) or cyclophosphamide.
- Universal RPGN rule: biopsy + serologies, then immunosuppress early — outcome tracks how fast you treat.
"Low-complement" nephritis (↓C3) — immune complexes are being consumed:
- PSGN, MPGN, Lupus (↓C3 and ↓C4), cryoglobulinemia, sub-acute endocarditis.
- Everything else — IgA, anti-GBM, ANCA, Alport — has normal complement.
Biopsy image = diagnosis (real classics):
- Subepithelial humps / lumpy-bumpy "starry sky" → PSGN
- Linear IF → anti-GBM (Linear = Lungs + kidney)
- Wire-loop (subendothelial) → Lupus (both start with L)
- Tram-track (double contour) → MPGN
- Basket-weave GBM → Alport (can't see, can't hear, can't pee)
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