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BASICS

Description

  • Acute GN is an inflammatory or immune-mediated process involving the kidney glomerulus.
  • Clinical presentation: sudden hematuria, proteinuria, renal insufficiency.
  • Can be primary or secondary to systemic diseases.
  • Severity varies from asymptomatic hematuria to rapidly progressive loss of kidney function.

Alert: Urgent investigation and treatment needed to prevent irreversible kidney damage and chronic kidney disease (CKD).

Epidemiology

  • Postinfectious GN: common in children; occurs 1-3 weeks post-group A β-hemolytic streptococcus infection.
  • Other infectious causes: bacterial (endocarditis, VP shunt nephritis), viral, helminthic, parasitic.
  • IgA nephropathy: most common primary GN worldwide; mostly in 2nd and 3rd decades; higher incidence in Asia.
  • Henoch-Schönlein purpura (HSP): typically in children <10 years.
  • Anti-GBM disease (Goodpasture syndrome): peaks in 3rd and 6th decades.
  • ANCA-associated GN: relapsing-remitting course with several clinical phenotypes.
  • Membranoproliferative GN (MPGN): primary or secondary; often subacute or chronic.
  • Lupus nephritis: affects ~60% of SLE patients; higher incidence in Black and Hispanic populations.
  • Cryoglobulin-associated vasculitis: linked with hepatitis C infection (~80% of cases).
  • Prevalence: 1.2% in >65 years old; 0.12% in 37-65 years; incidence in children unknown but postinfectious GN is common.

Etiology and Pathophysiology

  • Immune activation causes glomerular injury.
  • Immune complex-mediated: antigen-antibody deposition (e.g., postinfectious GN, IgA nephropathy, MPGN, lupus nephritis, cryoglobulinemic GN).
  • Direct antibody-mediated (linear staining): anti-GBM disease.
  • Pauci-immune GN (no immune complex staining): ANCA-associated GN.
  • Alternative complement pathway dysregulation: C3 glomerulopathy.

Risk Factors

  • Epidemics of nephritogenic streptococci (postinfectious GN).
  • Pulmonary injury and exposure to hydrocarbons (anti-GBM disease).
  • Drugs (hydralazine, levamisole-contaminated cocaine) and silica exposure (ANCA-associated GN).
  • Hepatitis B (MPGN), hepatitis C (MPGN, cryoglobulinemic GN).

DIAGNOSIS

History

  • Symptoms: cola/tea-colored urine, oliguria, blurred vision, dizziness, headache, altered mental status, edema, dyspnea, malaise.
  • Timing: poststreptococcal GN 1-3 weeks after pharyngitis, 2-6 weeks after skin infection.
  • Disease-specific symptoms:
  • Lupus nephritis: joint pain, rash.
  • Pulmonary-renal syndromes: hemoptysis.
  • ANCA GN: sinusitis, pulmonary infiltrates, arthralgias.
  • IgA-HSP: abdominal/joint pain, purpura.
  • Cryoglobulinemic GN: purpura, vasculitis.

Physical Exam

  • Often normal; may have hypertension, fluid overload signs.
  • Sinus disease in ANCA/GPA.
  • Pharyngitis/impetigo in postinfectious GN or IgA nephropathy.
  • Pulmonary hemorrhage in anti-GBM, ANCA GN, lupus nephritis.
  • Hepatomegaly in cryoglobulinemic GN or IgA nephropathy.
  • Purpura in ANCA GN or HSP.

Differential Diagnosis

  • Non-glomerular hematuria: trauma, prostate disease, urologic cancer, cystitis, nephrolithiasis, renal cysts, thrombotic microangiopathy.

Diagnostic Tests & Interpretation

Initial Tests

  • Urinalysis: dysmorphic RBCs and RBC casts indicate glomerular hematuria.
  • Proteinuria: 24-hour or urine protein-to-creatinine ratio.
  • Blood tests: electrolytes, BUN, creatinine, CBC.
  • Serologies:
  • Antistreptolysin O titer, streptozyme (postinfectious GN).
  • Complement (C3, C4).
  • ANA (lupus nephritis).
  • ANCA screen (MPO, PR3 antibodies).
  • Anti-GBM antibody.
  • Hepatitis B/C serology.
  • Cryoglobulins.
  • Rheumatoid factor.
  • HIV test.
  • Serum free light chain (monoclonal gammopathy).
  • Imaging:
  • Renal ultrasound to exclude structural causes.
  • Chest X-ray if hemoptysis or lung infiltrates.

Definitive Diagnosis

  • Renal biopsy:
  • Light microscopy: diffuse hypercellularity, crescents (RPGN).
  • Immunofluorescence: pattern of immunoglobulin/complement deposition.
    • Lupus: full house (IgG, IgA, IgM, C3, C4).
    • IgA nephropathy: isolated mesangial IgA.
    • Pauci-immune: absent immune deposits.
    • Anti-GBM: linear IgG staining.
  • Electron microscopy: location of deposits guides diagnosis.

TREATMENT

General Measures

  • Treat underlying condition where possible.

Medications

  • First-line: diuretics, calcium channel blockers.
  • Avoid ACE inhibitors/ARBs if acute renal dysfunction present.
  • Postinfectious GN usually requires supportive care.
  • Crescentic GN: corticosteroids often indicated, sometimes prior to biopsy.
  • Additional immunosuppressives: cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors, rituximab.
  • Antiviral therapy for HCV or HBV-associated nephritic syndromes.
  • Plasmapheresis: RPGN or ANCA-associated GN with pulmonary hemorrhage.
  • Dialysis if uremic or refractory complications.

Referral

  • Nephrology for biopsy and management.
  • Rheumatology for systemic disease involvement.

Admission Considerations

  • Indicated for anuria, rapidly worsening renal function, uncontrolled hypertension, pulmonary hemorrhage, or fluid overload.

Ongoing Care and Follow-up

  • Monitor BP, urinalysis, renal function.
  • Regular clinical assessments for recurrence symptoms.
  • Repeat serologies as needed.
  • Salt restriction (<2 g/day) and fluid restriction during edema/hypertension.
  • Avoid potassium/phosphorus-rich foods if renal function severely impaired.

PATIENT EDUCATION

  • Refer to National Kidney Foundation resources.
  • Explain disease variability and importance of follow-up.
  • Recognize signs of recurrence or worsening.

PROGNOSIS

  • Variable: self-limited or chronic progressive.
  • Some forms require long-term immunosuppression to prevent relapse.
  • Potential progression to CKD.

COMPLICATIONS

  • Hypertensive retinopathy/encephalopathy.
  • Persistent microscopic hematuria.
  • Chronic kidney disease.
  • Nephrotic syndrome (~10%).

CLINICAL PEARLS

  • Dysmorphic RBCs and RBC casts strongly indicate glomerular source of hematuria.
  • Postinfectious GN in children is typically self-limited.
  • Look for systemic organ involvement to aid diagnosis.
  • Frequent renal function monitoring is key to identify RPGN.

REFERENCES

  1. Wetmore JB, Guo H, Liu J, et al. The incidence, prevalence, and outcomes of glomerulonephritis derived from a large retrospective analysis. Kidney Int. 2016;90(4):853-860.
  2. Beck L, Bomback AS, Choi MJ, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. Am J Kidney Dis. 2013;62(3):403-441.
  3. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2008;(3):CD003232.
  4. Jayne DRW, Gaskin G, Rasmussen N, et al; for European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180-2188.