Glomerulonephritis (GN): Complete Clinical Overview

1. Definition

2. Pathophysiology

A. Immune Complex Deposition (most common)

1. Deposit in the glomerular capillary walls (subendothelial, mesangial, or subepithelial locations)
2. Activate the complement cascade (particularly C3)
3. Trigger an intense inflammatory response with cellular proliferation
4. Reduce filtering surface area, causing oliguria and salt/water retention
5. Cause "bloodless capillaries" - disruption of capillary blood flow by proliferating cells

B. Anti-GBM Antibody Disease

C. ANCA-Associated Vasculitis (Pauci-Immune)

The RPGN Classification

• Type I - Anti-GBM antibody (Goodpasture syndrome, renal-limited)
• Type II - Immune complex (Low C3: postinfectious, SBE, hepatitis B/C, SLE, cryoglobulinemia, syphilis, schistosomiasis, tumors)
• Type III - ANCA-positive pauci-immune vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis)

3. Causes / Etiology

Primary (Idiopathic / Renal-Limited)

Secondary (Systemic Disease)

4. Clinical Presentation

Nephritic Syndrome (typical GN presentation)

• Hematuria - microscopic (dysmorphic RBCs) or macroscopic ("cola-colored" / "tea-colored" urine due to hematin formation in acid urine)
• Proteinuria (usually sub-nephrotic, <3.5 g/day)
• Oliguria / anuria - from reduced filtering surface area and prerenal Na+/water retention
• Hypertension - from volume expansion
• Edema - from salt and water retention; ascites in children; pulmonary edema in elderly
• Urinary sediment - RBC casts, dysmorphic RBCs, WBC casts (pathognomonic of GN)

Rapidly Progressive GN (RPGN) - Medical Emergency

• Days to weeks of declining renal function
• Crescents on biopsy (proliferating parietal epithelial cells + monocytes filling Bowman's space)
• Can lead to dialysis-dependent renal failure within weeks if untreated

Chronic GN

• Slow, irreversible progression to CKD and ESRD over years
• Third leading cause of CKD; accounts for ~10% of dialysis patients

5. Investigations

6. Treatment and Management

A. General / Supportive Management (all forms)

• Blood pressure control: ACE inhibitors (ACEi) or ARBs are first-line; they reduce intraglomerular pressure and proteinuria via anti-angiotensin II inhibition
• Dietary sodium restriction and diuretics for edema and hypertension
• Fluid management: Monitor fluid balance carefully given oliguria
• Treatment of underlying infection: Antibiotics for PSGN (if infection still present); drainage for abscesses
• Lipid management and cardioprotection in nephrotic-range proteinuria

B. Post-Infectious GN (PSGN)

• Mostly self-limiting - supportive care is the mainstay
• Penicillin/amoxicillin if active streptococcal infection persists
• Antihypertensives, diuretics for volume overload
• Full complement recovery expected within 6-8 weeks; prognosis is generally excellent in children

C. IgA Nephropathy

• ACEi/ARBs for proteinuria and hypertension
• Corticosteroids if proteinuria >1 g/day despite RAAS blockade
• Fish oil (omega-3): modest benefit in some patients
• Tonsillectomy historically used (limited evidence)
• Novel targeted therapies: complement pathway inhibitors (sparsentan, iptacopan) based on recent trials

D. ANCA-Associated Vasculitis (GPA, MPA)

• Rituximab (anti-CD20) + high-dose glucocorticoids (preferred, especially for severe/relapsing disease)
• OR Cyclophosphamide (IV pulse preferred over oral) + glucocorticoids

• Rituximab every 6 months for 18-24 months, OR
• Azathioprine or mycophenolate mofetil
• Gradual glucocorticoid taper

E. Anti-GBM Disease (Goodpasture)

• Plasmapheresis (daily for 14 days or until anti-GBM undetectable) - removes circulating antibody
• High-dose IV methylprednisolone → oral prednisone taper
• Cyclophosphamide (oral or IV) to suppress antibody production
• Dialysis if severe renal failure; kidney recovery unlikely if oligoanuric at presentation

F. Lupus Nephritis (Class III/IV)

• Mycophenolate mofetil (MMF) 2-3 g/day + glucocorticoids (preferred in most patients)
• OR IV cyclophosphamide + glucocorticoids
• Belimumab (add-on to MMF) has shown improved renal outcomes in recent trials
• Voclosporin (calcineurin inhibitor) + MMF is another approved induction regimen

• MMF 1-2 g/day + low-dose glucocorticoids (preferred over azathioprine in high-risk groups)
• Hydroxychloroquine in all SLE patients

G. Crescentic / RPGN (any etiology)

• IV methylprednisolone pulse (500-1000 mg/day x 3 days) → oral prednisone
• Immunosuppression (cyclophosphamide or rituximab depending on etiology)
• Plasma exchange for anti-GBM disease and severe ANCA vasculitis
• Dialysis support as needed

H. End-Stage Management

• If progression to ESRD despite treatment:
  • Hemodialysis or peritoneal dialysis
  • Kidney transplantation (wait for anti-GBM levels to normalize before transplant in Goodpasture; >12 months of seronegativity recommended)

7. Summary Table