Comprehensive Guide to Nephritic and Nephrotic Syndromes
Comprehensive guide featuring the latest treatment advances including voclosporin (Lupkynis), emerging biologics, and evidence-based protocols for young women
RPGN is a nephrology emergency! Any patient with β₯50% decline in GFR over days to weeks needs immediate nephrology consultation and urgent evaluation for rapidly progressive glomerulonephritis.
Glomerular diseases represent a complex group of disorders affecting the kidney's filtering units. This comprehensive chapter covers both nephritic and nephrotic syndromes, their pathophysiology, diagnostic approaches, and evidence-based treatments essential for PA practice.
Most important finding in nephritic syndrome
Measuring C3 and C4 simultaneously provides insight into which complement pathway is activated and helps narrow the differential diagnosis.
| Complement Pattern | Pathway | Renal-Limited Diseases | Systemic Diseases | % of Cases |
|---|---|---|---|---|
| Low C3 & C4 | Classical Pathway Activation |
β’ Idiopathic MPGN Type I β’ Dense deposit disease (rare) |
β’ SLE nephritis β’ Cryoglobulinemia β’ Subacute bacterial endocarditis β’ Shunt nephritis β’ Hepatitis C-associated GN |
~30% |
| Low C3, Normal C4 | Alternative Pathway Activation |
β’ Post-infectious GN β’ C3 glomerulopathy β’ Dense deposit disease |
β’ Atypical HUS β’ Partial lipodystrophy |
~25% |
| Normal C3 & C4 | No Complement Consumption |
β’ IgA nephropathy β’ Thin basement membrane β’ Renal-limited vasculitis β’ Anti-GBM nephritis |
β’ ANCA-associated vasculitis β’ Goodpasture syndrome β’ Henoch-SchΓΆnlein purpura β’ Alport syndrome β’ Polyarteritis nodosa |
~45% |
C-ANCA with sinusitis + pulmonary infiltrates + active urinary sediment = 98% PPV for GPA
However, C-ANCA with sinusitis alone has only 7-16% PPV
Use both immunofluorescence pattern AND antigen-specific ELISA (MPO/PR3) for optimal sensitivity and specificity
ANCA results must always be interpreted in the clinical context. PPV >95% in patients with classic RPGN features
Microscopic Polyangiitis (MPA)
Granulomatosis with Polyangiitis (GPA)
Note: African Americans and patients with collapsing FSGS are generally unresponsive to treatment and progress to kidney failure.
| Risk Category | Criteria | Management |
|---|---|---|
| Low Risk | Normal eGFR, Proteinuria <3.5 g/day, Serum albumin >3.0 g/dL | Supportive care only |
| Moderate Risk | Proteinuria 3.5-8 g/day, Stable eGFR, Albumin 2.5-3.0 g/dL | Rituximab or calcineurin inhibitors |
| High/Very High Risk | Proteinuria >8 g/day, Declining eGFR, High anti-PLA2R levels (>150 RU/mL) | Immunosuppressive treatment required |
Pathophysiology: Loss of antithrombin III and protein S, increased fibrinogen and platelets, hemoconcentration from diuretic use
Management: Consider prophylactic anticoagulation if albumin <2.0 g/dL
Pathophysiology: Loss of immunoglobulins in urine, complement factor losses, immunosuppressive medications
RPGN is a clinical syndrome characterized by rapid decline in glomerular filtration rate of at least 50% over days to 3 months, often progressing to kidney failure without prompt treatment.
Greater than or equal to 50% decline over days to 3 months
Hematuria, dysmorphic RBCs, RBC casts, proteinuria
Greater than 50% of glomeruli on biopsy
Constitutional symptoms, fever, malaise, arthralgias
Pathophysiology: Autoantibodies against NC1 domain of Ξ±3 chain of type IV collagen in glomerular and alveolar basement membranes
| Type | Pattern | Main Causes | % of RPGN | Treatment Priority |
|---|---|---|---|---|
| Type I | Linear (Anti-GBM) | Goodpasture's, Anti-GBM nephritis | 10% | Plasmapheresis + Immunosuppression |
| Type II | Granular (IC) | Lupus, Post-infectious, IgA | 40% | Treat underlying cause |
| Type III | Pauci-immune | ANCA-associated vasculitis | 50% | Steroids + Cyclophosphamide/Rituximab |
RPGN Emergency: Any patient with rapid decline in kidney function (>50% over weeks) needs immediate nephrology consultation. Don't wait for urine microscopy results.
RBC casts indicate glomerulonephritis and mandate immediate glomerular disease workup. Fresh urine examination within 2 hours is critical for detection.
Normal C3/C4: Think ANCA-associated, IgA nephropathy, or anti-GBM. Low C3 only: Post-infectious or C3 glomerulopathy. Low C3/C4: SLE or endocarditis.
C-ANCA with sinusitis + lung nodules + active urine sediment = 98% PPV for GPA. Always correlate ANCA results with clinical presentation.
Watch for thromboembolism (hypercoagulable state), infections (immunoglobulin loss), and protein malnutrition. Consider prophylactic anticoagulation.
Positive anti-PLA2R with nephrotic syndrome can diagnose membranous nephropathy without biopsy (78% sensitivity, 99% specificity).
Serial determinations are always a better guide to disease activity than single measurements. Monitor C3/C4 levels over time.
RBC casts may dissolve in older urine specimens. Examine fresh urine (<2 hours) when possible for accurate diagnosis.
Consider prophylactic anticoagulation if serum albumin <2.0 g/dL due to high thromboembolism risk.
In PLA2R-positive membranous nephropathy, the goal should be complete disappearance of anti-PLA2R antibodies.
Always screen adults with new nephrotic syndrome for secondary causes, especially malignancy and systemic disease.
Hemoptysis plus rapidly declining kidney function = medical emergency. Consider anti-GBM disease, ANCA vasculitis, or SLE.
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