Nephritic syndrome

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nephritic syndrome glomerulonephritis histology pathology

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glomerulonephritis post-streptococcal IgA nephropathy RPGN anti-GBM ANCA

Here is a comprehensive overview of nephritic syndrome:

Nephritic Syndrome

Definition

Nephritic syndrome is a clinical constellation resulting from glomerular inflammation that causes disruption of the capillary wall, leading to hematuria, proteinuria, oliguria, hypertension, and varying degrees of renal impairment.

Core Features (The "Nephritic Pentad")

Feature	Mechanism
Hematuria (macro or microscopic)	Disrupted GBM allows RBC passage
Proteinuria (usually < 3.5 g/day)	Inflammatory damage to filtration barrier
Oliguria	Reduced GFR from inflammation
Hypertension	Salt/water retention; ↑ RAAS
Azotemia	Impaired glomerular filtration

The nephritic urinalysis is hallmark: hematuria, RBC casts, granular casts, WBC casts, and mixed proteinuria. RBC casts are pathognomonic for glomerulonephritis. (Harrison's, p. 8381)

Pathophysiology

Glomerular inflammation involves:

Immune complex deposition (in situ or circulating) → complement activation → C3a/C5a recruitment of PMNs
Endocapillary hypercellularity → obliteration of capillary lumens → ↓ GFR
Crescent formation (in severe disease) → parietal epithelial cell proliferation + macrophage infiltration in Bowman's space → rapidly progressive GN (RPGN)
Salt/water retention → hypertension and edema (less dramatic than nephrotic)

Causes and Classification

By Pattern of Injury

Category	Prototype Diseases
Diffuse proliferative GN	Post-infectious GN (PSGN), lupus nephritis class III/IV
Mesangial proliferative GN	IgA nephropathy (Berger's disease)
RPGN / Crescentic GN	Anti-GBM (Goodpasture), ANCA vasculitis, immune complex GN
Focal proliferative GN	IgA nephropathy, lupus class III

By Immunofluorescence Pattern

IF Pattern	Diagnosis
Granular ("starry sky")	PSGN, lupus, IgA nephropathy, MPGN
Linear	Anti-GBM disease (Goodpasture syndrome)
Pauci-immune (negative/scant)	ANCA-associated vasculitis (GPA, MPA, EGPA)

Key Individual Conditions

1. Post-Streptococcal GN (PSGN)

Trigger: Group A β-hemolytic Strep (pharyngitis or impetigo), 1–3 weeks prior
Age: Children most common; can affect adults
Labs: ↓ C3, normal C4; ASO/anti-DNase B positive
Course: Self-limiting in children; adults may have persistent disease

2. IgA Nephropathy (Berger's Disease)

Most common primary GN worldwide
Gross hematuria concurrent with URI ("synpharyngitic hematuria")
Mesangial IgA deposits on IF
Prognosis variable; ~30% progress to ESRD over 20 years

3. Lupus Nephritis

WHO/ISN Class III/IV presents as nephritic syndrome
↓ C3 and C4; anti-dsDNA, ANA positive
"Full house" immunofluorescence (IgG, IgA, IgM, C3, C4, C1q)

4. RPGN / Crescentic GN

Rapid loss of renal function over days–weeks
50% crescents on biopsy
Three types:
- Type I: Anti-GBM (linear IF) — Goodpasture syndrome (pulmonary hemorrhage + nephritis)
- Type II: Immune complex (granular IF)
- Type III: Pauci-immune (ANCA+) — GPA, MPA

5. Membranoproliferative GN (MPGN)

Can present with mixed nephritic-nephrotic features
↓ C3; "tram-track" GBM on EM
Associated with hepatitis C, cryoglobulinemia, complement disorders

Histology

RPGN with crescent formation — light microscopy (H&E)

Renal biopsy showing intraglomerular hypercellularity, prominent cellular crescent in Bowman's space compressing the capillary tuft, and surrounding interstitial inflammation — consistent with RPGN/crescentic GN.

Diagnosis

Workup Algorithm

Urinalysis + microscopy — RBC casts confirm glomerulonephritis
CBC, BMP, LFTs — assess renal function, anemia
24-hour urine protein or spot PCR — quantify proteinuria
Complement (C3, C4, CH50)
Serologies:
- ANA, anti-dsDNA (lupus)
- ANCA (p-ANCA/MPO, c-ANCA/PR3)
- Anti-GBM antibodies
- ASO, anti-DNase B (PSGN)
- HBsAg, anti-HCV, cryoglobulins
- Serum protein electrophoresis
Renal biopsy — required for definitive diagnosis in most cases (except classic PSGN)

Complement Levels as a Diagnostic Aid

Condition	C3	C4
PSGN	↓	Normal
Lupus nephritis	↓	↓
MPGN	↓	↓ or normal
Anti-GBM, ANCA	Normal	Normal
IgA nephropathy	Normal	Normal

Management

General Principles

Treat underlying cause (specific therapy below)
BP control: ACE inhibitors/ARBs (also reduce proteinuria)
Salt/fluid restriction: manage hypertension and edema
Loop diuretics: for volume overload
Dialysis: if severe AKI or uremia

Disease-Specific Treatment

Disease	Treatment
PSGN	Supportive (antibiotics if active infection; steroids not routinely indicated)
IgA nephropathy	ACE/ARB; fish oil; steroids if proteinuria >1g/day; sparsentan (newer agent)
Lupus nephritis III/IV	Hydroxychloroquine + MMF or cyclophosphamide + steroids; belimumab, voclosporin (newer)
Anti-GBM disease	Urgent plasmapheresis + cyclophosphamide + steroids
ANCA vasculitis	Rituximab or cyclophosphamide + steroids; rituximab preferred for GPA/MPA
MPGN	Treat underlying cause (HCV: antivirals; complement: eculizumab)

Nephritic vs. Nephrotic Syndrome (Quick Comparison)

Feature	Nephritic	Nephrotic
Proteinuria	< 3.5 g/day	> 3.5 g/day
Hematuria	Prominent	Minimal
RBC casts	Yes	No
Edema	Mild–moderate	Severe ("pitting")
Hypertension	Common	Variable
Mechanism	Inflammation	Podocyte injury

Prognosis

PSGN in children: >95% full recovery
IgA nephropathy: 20–40% ESRD over 20 years; Oxford MEST-C score guides prognosis
Lupus nephritis class IV: renal survival ~80% at 10 years with treatment
Anti-GBM disease: poor if dialysis-dependent at presentation; aggressive early treatment critical
RPGN (ANCA): good renal recovery if treated promptly; relapse common

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