Renal/Urology · PANCE / PANRE

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.

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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'

Differentiating glomerulonephritides by complement status, serology, and immunofluorescence pattern.

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)

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