Nephritic Syndrome
Glomerular inflammation with hematuria, RBC casts, hypertension, and mild-to-moderate proteinuria.
Also known as: nephritic syndrome, glomerulonephritis, GN, RPGN
Overview
Clinical syndrome resulting from glomerular inflammation, characterized by hematuria (often with dysmorphic RBCs and RBC casts), variable proteinuria (typically <3.5 g/day), hypertension, edema, and azotemia. Spans a spectrum from indolent to rapidly progressive glomerulonephritis (RPGN).
Epidemiology
Incidence varies by etiology. Post-streptococcal GN is the most common cause worldwide in children. IgA nephropathy is the most common primary glomerulonephritis globally. ANCA-associated vasculitis and lupus nephritis dominate adult RPGN.
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Nephritic Syndrome outline — plus all 514 diagnoses, 5,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Risk factors
- Recent infection: streptococcal (post-strep GN), staphylococcal, hepatitis B/C
- Autoimmune disease: SLE, ANCA vasculitis, anti-GBM (Goodpasture)
- Family history: Alport syndrome, IgA nephropathy
- Cryoglobulinemia (often hep C-related)
- Recent URI (synpharyngitic hematuria of IgA nephropathy)
Pathophysiology
Immune-mediated glomerular injury — immune complex deposition, in situ antibody formation, or pauci-immune inflammation — disrupts the filtration barrier and triggers proliferative changes. Endothelial and mesangial inflammation allow RBC passage into Bowman space, generating dysmorphic RBCs and RBC casts. Loss of nephron mass causes azotemia and sodium retention → hypertension and edema.
Clinical presentation
Symptoms
- Cola-colored, tea-colored, or smoky urine (gross hematuria)
- Periorbital and peripheral edema
- Headache, malaise (from hypertension)
- Oliguria in severe or rapidly progressive cases
- Constitutional symptoms (fever, weight loss, arthralgia) in systemic vasculitis or SLE
Signs / physical exam
- Hypertension (sometimes severe)
- Periorbital edema, peripheral edema
- Skin findings: palpable purpura (IgA vasculitis, cryoglobulinemia), malar rash (SLE)
- Respiratory: hemoptysis suggests pulmonary-renal syndrome (anti-GBM, ANCA)
- Sinusitis, saddle-nose deformity in GPA
Classic findings
Tea-colored urine plus periorbital edema and hypertension in a child 1-3 weeks after sore throat — classic for post-streptococcal GN.
Differential diagnosis
- IgA nephropathy — Synpharyngitic hematuria (within days of URI), mesangial IgA deposits; common in young adults
- Post-streptococcal GN — 1-3 weeks after group A strep pharyngitis or impetigo; low C3, normal C4; positive ASO/anti-DNase B
- Anti-GBM disease (Goodpasture) — Pulmonary hemorrhage + RPGN; linear IgG on biopsy; anti-GBM antibody positive
- ANCA-associated vasculitis (GPA, MPA, EGPA) — Pauci-immune crescentic GN; c-ANCA (PR3) in GPA; p-ANCA (MPO) in MPA/EGPA; sinopulmonary involvement
- Lupus nephritis — SLE features; ANA, anti-dsDNA, low C3/C4; biopsy classes I-VI guide therapy
- Membranoproliferative GN (MPGN) — Mixed nephritic/nephrotic; low C3; hepatitis C with cryoglobulinemia, monoclonal gammopathy
- Alport syndrome — Hereditary X-linked; hematuria, sensorineural hearing loss, lenticonus; type IV collagen mutation
- Thin basement membrane disease — Benign familial hematuria; isolated microhematuria; thin GBM on EM; preserved function
Diagnostic workup
Diagnostic criteria
Nephritic syndrome = hematuria (often gross) with RBC casts and dysmorphic RBCs + variable proteinuria + hypertension + azotemia. Kidney biopsy is the definitive test for adults and complicated pediatric cases to determine pattern and guide immunosuppression.
Labs
- Urinalysis with microscopy — dysmorphic RBCs, RBC casts (diagnostic of glomerular bleed)
- Spot UPCR or 24-h urine protein
- BMP, CBC, creatinine trend
- Complement: C3 and C4 (low in post-strep, lupus, MPGN, cryoglobulinemia; normal in IgA, anti-GBM, ANCA)
- ANA, anti-dsDNA (lupus); ANCA with PR3/MPO; anti-GBM antibody
- ASO, anti-DNase B (post-strep)
- Hepatitis B/C serologies, HIV; cryoglobulins; SPEP/UPEP
Imaging
- Renal ultrasound to assess size and exclude obstruction
- Chest imaging if pulmonary symptoms or suspected pulmonary-renal syndrome
Diagnostic algorithm
| Disease | Complement | Key Serology | Biopsy IF Pattern |
|---|---|---|---|
| Post-streptococcal GN | Low C3, normal C4 | ASO, anti-DNase B | Granular IgG/C3, 'humps' |
| IgA nephropathy | Normal | (galactose-deficient IgA1) | Mesangial IgA |
| Lupus nephritis | Low C3 and C4 | ANA, anti-dsDNA, anti-Sm | 'Full house' (IgG, IgA, IgM, C3, C1q) |
| Anti-GBM (Goodpasture) | Normal | Anti-GBM antibody | Linear IgG along GBM |
| ANCA (GPA/MPA) | Normal | c-ANCA/PR3 or p-ANCA/MPO | Pauci-immune crescentic |
| MPGN | Low C3 ± low C4 | Cryoglobulins, hep C | Subendothelial deposits, 'tram-tracking' |
Treatment
First-line
- Treat underlying etiology — antibiotics for active infection, immunosuppression for autoimmune cause
- BP control: ACEi or ARB (lisinopril, losartan); avoid in acute AKI exacerbation
- Loop diuretic — furosemide, torsemide — for volume overload
- Sodium and fluid restriction
- Empiric pulse methylprednisolone (1 g IV daily × 3) for biopsy-proven or strongly suspected RPGN while definitive workup pending
Second-line / adjunct
- ANCA vasculitis: induction with rituximab or cyclophosphamide + glucocorticoids; plasma exchange for severe pulmonary hemorrhage or anti-GBM disease
- Anti-GBM disease: plasma exchange + cyclophosphamide + steroids
- Lupus nephritis: mycophenolate or cyclophosphamide + glucocorticoids; voclosporin or belimumab as add-on
- Cryoglobulinemic GN: treat underlying hep C with direct-acting antivirals; rituximab for refractory
- Hemodialysis if uremia, refractory hyperkalemia, or volume overload not responding to medical therapy
Complications
- Rapidly progressive renal failure (RPGN)
- Hypertensive emergency, posterior reversible encephalopathy syndrome (PRES)
- Pulmonary hemorrhage (anti-GBM, ANCA, lupus)
- Volume overload, heart failure
- Progression to CKD/ESRD
- Treatment-related: infection from immunosuppression, cyclophosphamide bladder toxicity, steroid morbidity
PANCE pearls
- RBC casts = glomerular bleeding until proven otherwise. Dysmorphic RBCs (especially acanthocytes) also localize to the glomerulus.
- Complement classification of GN: LOW C3 = post-strep, MPGN, lupus, cryoglobulinemia. NORMAL C3 = IgA, anti-GBM, ANCA, HSP/IgA vasculitis.
- Pulmonary-renal syndrome (hemoptysis + AKI) = anti-GBM disease, GPA, MPA, or lupus. Send anti-GBM and ANCA urgently.
- RPGN = loss of >50% kidney function in days to weeks; biopsy shows crescents in >50% of glomeruli. Treat empirically while awaiting biopsy.
- Post-strep GN has excellent prognosis in children; adults more likely to develop CKD.
References
- KDIGO 2021 — KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases
- EULAR/ERA-EDTA 2024 — EULAR Recommendations for the Management of ANCA-Associated Vasculitis: 2022 Update (Hellmich et al., 2024)
- ACR 2024 — ACR Guideline for the Treatment of Lupus Nephritis (Arthritis Rheumatol 2024)
Practice Renal/Urology questions on FirstPassPA
Turn this outline into retention. 5,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Start studying free → Browse all 514 diagnosesEducational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.