Nephritic syndrome and glomerulonephritis

Definition

Nephritic syndrome is the clinical expression of glomerular inflammation (glomerulonephritis). Its hallmarks are hematuria with usually dysmorphic red blood cells and often red blood cell casts, together with variable proteinuria. Edema, hypertension, a rise in creatinine and oliguria are often present as well.

Classification

Types

• Acute glomerulonephritis: creatinine rises over days to weeks; the prototype is postinfectious glomerulonephritis
• Rapidly progressive glomerulonephritis: kidney failure within weeks to months with crescent formation
• Chronic glomerulonephritis: slow course over years with mild to moderate proteinuria, e.g. IgA nephropathy, Alport syndrome
• In addition, primary (kidney-limited) and secondary forms due to infections or systemic diseases are distinguished.

Aetiopathogenesis

• Primary: IgA nephropathy, membranoproliferative glomerulonephritis, idiopathic crescentic glomerulonephritis
• Infection-related: group A streptococci, staphylococci (especially endocarditis), hepatitis B and C, visceral abscesses, malaria
• Systemic diseases: systemic lupus erythematosus, IgA vasculitis, ANCA-associated vasculitides, anti-GBM disease, cryoglobulinemia, hemolytic uremic syndrome
• Hereditary: Alport syndrome, thin basement membrane disease

Postinfectious glomerulonephritis is the most common acute glomerulonephritis in children aged 3 to 15 years. It typically follows pharyngitis or impetigo due to nephritogenic group A streptococci after 6–21 days (up to 6 weeks). Microbial antigens and immune complexes deposit in the glomeruli and activate mainly the alternative complement pathway.

Clinical features

The spectrum ranges from asymptomatic microscopic hematuria to the full picture with cola- or smoke-colored urine, oliguria, edema, hypertension and acute kidney injury. Systemic diseases additionally present with skin lesions, joint symptoms, hemoptysis or constitutional symptoms. Fever is unusual in the postinfectious form and suggests persistent infection.

Histology

In postinfectious glomerulonephritis, the glomeruli are enlarged and hypercellular, with initial neutrophilic infiltration, proliferation of endothelial and mesangial cells and subepithelial electron-dense deposits; crescents form in severe cases.

Diagnosis

• Urine sediment: glomerular red cells are smaller and dysmorphic (spicules, folding, blebs); red blood cell casts and dysmorphic red cells indicate glomerulonephritis or vasculitis.
• Quantify proteinuria (protein-to-creatinine ratio); in the postinfectious form usually 0.2–2, occasionally in the nephrotic range
• Kidney function: creatinine, urea, electrolytes
• Complement: low C3 (and CH50) in postinfectious glomerulonephritis, usually normalizing within 6–8 weeks; low C3 and C4 also in active lupus nephritis
• Serology: antistreptolysin O, anti-DNase B, antinuclear and anti-dsDNA antibodies, ANCA, anti-GBM antibodies, hepatitis serology
• Kidney biopsy with light microscopy, immunofluorescence and electron microscopy to determine the cause

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Overview of Nephritic Syndrome
2. MSD Manual Professional: Postinfectious Glomerulonephritis (PIGN)
3. MSD Manual Professional: Evaluation of the Patient With Renal Issues
4. MSD Manual Professional: Acute Kidney Injury (AKI)
5. MSD Manual Professional: Lupus Nephritis

Cross-references