Glomerular disease
Nephrotic: ≥3.5 g/day + albumin <3. Loop diuretics, salt restriction, statin, ACE/ARB, VTE ppx if albumin <2 (especially membranous).
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Nephrotic vs nephritic
Nephrotic
- ↓ podocyte integrity → glomerular proteinuria, mostly albumin.
- 24h UPr >3.5 g/day or spot PCR >3.5 g/g AND albumin <3.0 (that pair is the syndrome; nephrotic-range protein without hypoalbuminemia is not).
- Edema / anasarca, HLD + premature atherosclerosis, foamy urine.
- Hypercoagulability (10–40% VTE from loss of antithrombin and plasminogen).
- Vitamin D deficiency (loss of binding protein), infection risk (↓IgG / opsonins), protein malnutrition.
Nephritic
- Immune-mediated endothelial and podocyte injury → hematuria with an active sediment.
- AKI (azotemia → oliguria), HTN, often periorbital edema, proteinuria, hematuria, hypercoagulability.
- Systemic vasculitis extras: fatigue, fever, weight loss, palpable purpura, DAH, mononeuritis multiplex, SLE features.
- RPGN: renal failure in weeks–months, ↓GFR >50% in ~3 months, >50% crescents, typically sub-nephrotic protein, dysmorphic RBCs.
| Complement | Think |
|---|---|
| Low (↓C3 ± ↓C4) | PSGN, SLE, cryoglobulinemia, MPGN / C3GN, endocarditis. Complements split the nephritic differential in half. |
| Normal | IgA / HSP, ANCA, anti-GBM, fibrillary (DNAJB9). IgA does not fix complement. |
Nephrotic syndrome
Workup: UA, HbA1c, ANA, anti-dsDNA, anti-PLA2R, THSD7A, SPEP/SFLC, HBV, HCV, HIV, syphilis, cryoglobulins, C3/C4, renal biopsy. Low muscle mass overestimates proteinuria on spot ratios; high muscle mass underestimates them.
- Edema: loop diuretics first-line, augment with thiazides if resistant, plus Na <2 g/day.
- HLD: statin.
- VTE prophylaxis: consider especially if membranous, serum albumin <2 g/dL, proteinuria >10 g/day, or BMI >35.
- ACE inhibitor / ARB to ↓ glomerular pressure.
- Steroids or other immunosuppression depends on disease — typically high-dose glucocorticoids. See .
| Disease | Associations / treatment | Biopsy |
|---|---|---|
| Diabetes | T1DM and T2DM, retinopathy / neuropathy. The most common adult nephrotic picture — still exclude other GNs if atypical. | Nodular glomerulosclerosis |
| FSGS | Primary: toxin or circulating permeability factor → podocyte effacement / loss. Secondary: viral (HIV, parvo, EBV, CMV); drugs (NSAIDs, pamidronate, interferon, rapamycin, heroin, lithium, anabolic steroids, mTOR inhibitors); adaptive (nephrectomy, CKD, obesity, reflux, HTN); chronic hypoxemia (OSA, sickle cell). | Focal / segmental sclerosis on LM. Collapsing variant (HIV, SLE, APOL1) races to ESRD. |
| Membranous | Primary: anti-PLA2R (75%), highly specific (), or THSD7A. Secondary: SLE, HBV, syphilis, drugs (NSAIDs, penicillamine, gold), solid tumors. Tx: rituximab, or cyclophosphamide + steroids (, Figures 30–31). | Thick BM with dense subepithelial deposits (IF, EM); no cellular infiltrates. |
| Minimal change | Idiopathic; associated with NSAIDs, lymphoma (Hodgkin most commonly), children > adults, anti-nephrin autoantibodies (). | Podocyte foot-process effacement on EM. LM is normal. |
| Amyloidosis | AL (myeloma) and AA (systemic inflammation — RA, IBD). | Diffuse amorphous hyaline deposits; Congo-red positive. IF light-chain restriction in AL. |
Glomerulonephritis
Workup: UA/sediment (dysmorphic RBCs — specific, less sensitive), RBC casts (rare, very specific), sub-nephrotic proteinuria (<3.5 g/day, but 10–30% spill >3 g/day). Serologies below. Early renal consult for biopsy and steroids.
- Treat the cause (antibiotics, antivirals, stop the drug), BP, diuresis, low-Na diet.
- Biopsy guides immunosuppression. If the pretest for ANCA vasculitis is high, consider empiric IV methylprednisolone pulse 0.5–1 g × 3 days while awaiting biopsy, then cyclophosphamide (CYC) or rituximab (RTX).
- ANCA RPGN induction: steroids + RTX or CYC (RAVE, ). Maintenance: RTX > AZA ().
- Induction without PLEX and with reduced-dose steroids appears non-inferior and lowers infection risk (PEXIVAS, ) — PLEX still for anti-GBM, selected ANCA with DAH or dialysis dependence, and CAPS.
| Disease | Clues and treatment | Labs |
|---|---|---|
| Post-infectious / infection-related GN | ~1–2 weeks after pharyngitis, 3–6 weeks after cellulitis, or ongoing infection in adults. ↓C3 for >12 weeks may warrant biopsy to exclude C3GN. No benefit to steroids. | ↑ASO, anti-DNase B, anti-hyaluronidase; ↓C3 ± ↓C4 |
| Fibrillary GN | Idiopathic; cancer; autoimmune (Crohn, SLE, Graves, ITP). | Normal C3 (IF/EM +DNAJB9) |
| IgA nephropathy | Primary: ~1–2 days after URI, GI infection, or none. Secondary: liver disease, celiac, HIV. Tx: nefecon, sparsentan, iptacopan, atrasentan, sibeprenlimab. | ± ↑IgA, normal C3; biopsy for diagnosis |
| SLE (classes III, IV) | Photosensitivity, malar rash, sicca, pleuritis, cytopenias, arthralgias. See . | ↑ANA, ↑anti-dsDNA, ↑anti-Sm, ↓C3, ↓C4 |
| Cryoglobulinemia (type II) | HCV > HBV, ESLD, myeloma. | ↑cryos (↑↑RF), ↑HCV, ↓C3, ↓↓C4 |
| MPGN | Immune-complex: chronic infection (HCV > HBV, endocarditis, abscess); AI (SLE > Sjögren, RA); monoclonal gammopathies; lymphoma, solid tumors. Complement: dense-deposit disease or C3/C4 glomerulonephritis. | Thick BM, mesangial proliferation, subendothelial ± subepithelial deposits |
| Infective endocarditis | Fever, valve disease, emboli. MPGN or pauci-immune pattern. | ↑blood cultures, ↓C3, ANCA (can be induced) |
| IgA vasculitis (HSP) | Nephropathy, purpura, arthritis, GI bleed; typically children. | ↑IgA, normal C3 (IgA does not fix complement) |
| GPA | Granulomatous sinusitis/otitis, other ENT, lung (DAH, granuloma), arthritis, palpable purpura, RPGN. | c-ANCA / anti-PR3 (80%); p-ANCA / anti-MPO (10%) |
| EGPA | Multisystem, new-onset asthma, allergic rhinitis/sinusitis, mononeuritis multiplex. | p-ANCA / anti-MPO (50%), eos ≥1,500 |
| Microscopic polyangiitis | Multisystem, non-granulomatous. | Anti-MPO (60–70%) |
| Drug-induced vasculitis | Hydralazine, PTU, allopurinol, adulterated cocaine (levamisole → ear necrosis). | High-titer p-ANCA (95% of drug-induced; MPO, HNE); c-ANCA (50%; anti-histone) |
| Anti-GBM / Goodpasture | Crescentic RPGN; DAH (Goodpasture = hematuria + hemoptysis). Pulse steroids + CYC + plasmapheresis. | Linear IgG along BM, ↑anti-GBM IgG |
| Alport syndrome | Mutant COL4A (kidney, hearing, eye); familial. | EM with split GBM; COL4A3–5 testing |