pharmacological treatment for glomerulonephritis
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Pharmacological Treatment of Glomerulonephritis
Management is highly disease-specific. Treatment must balance the risk of disease progression against the toxicity of the drugs used. Below is a drug-class overview followed by disease-specific approaches.
1. Corticosteroids
The backbone of immunosuppression in GN.
- High-dose oral prednisone (e.g., 1 mg/kg/day up to 80 mg/day) is standard induction in minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN).
- IV methylprednisolone pulses (500–1000 mg/day × 3 days) are used in rapidly progressive GN (RPGN) and crescentic GN before oral steroids.
- Toxicities: hyperglycemia, hypertension, osteoporosis, adrenal suppression, infection, weight gain, cataracts. Cumulative dose and duration must be minimized.
2. Calcineurin Inhibitors (CNIs)
- Cyclosporine and tacrolimus inhibit T-cell activation via calcineurin blockade.
- Used in: steroid-dependent/resistant MCD, FSGS, MN (especially as steroid-sparing agents), and lupus nephritis (LN).
- Tacrolimus is preferred over cyclosporine due to a better side-effect profile (less hirsutism, gingival hyperplasia).
- Key toxicities: nephrotoxicity (dose-dependent), hypertension, hyperkalemia, neurotoxicity (tacrolimus).
- Therapeutic drug monitoring (trough levels) is essential.
3. Alkylating Agents
- Cyclophosphamide (CYC) — oral or IV pulse (NIH protocol).
- First-line induction for ANCA-associated vasculitis/crescentic GN (with high-dose steroids).
- Used in severe lupus nephritis (class III/IV).
- Also used in MN and fibrillary GN.
- Toxicities: hemorrhagic cystitis (prevent with hydration ± mesna), myelosuppression, gonadal toxicity (cumulative dose-dependent), bladder cancer, opportunistic infections.
- Chlorambucil — alternative alkylating agent, largely replaced by cyclophosphamide.
4. Mycophenolic Acid (MPA) / Mycophenolate Mofetil (MMF)
- Inhibits inosine monophosphate dehydrogenase → blocks de novo purine synthesis in lymphocytes.
- Standard of care for lupus nephritis (both induction and maintenance); non-inferior to IV cyclophosphamide in many trials.
- Used in IgA nephropathy, MN (as part of combination regimens), and FSGS.
- Teratogenic — mandatory pregnancy counseling and contraception.
- Toxicities: GI (diarrhea, nausea), leukopenia, infection risk.
5. Azathioprine
- Purine analog; inhibits DNA synthesis in proliferating lymphocytes.
- Primarily a maintenance agent in ANCA vasculitis (after remission with cyclophosphamide).
- Also used in lupus nephritis maintenance.
- Toxicities: myelosuppression, hepatotoxicity, pancreatitis. TPMT/NUDT15 genotyping before use is advisable.
6. Rituximab (Anti-CD20 Monoclonal Antibody)
- Depletes B cells → reduces autoantibody production.
- ANCA-associated vasculitis: rituximab is non-inferior to cyclophosphamide for induction (RAVE and RITUXVAS trials) and is preferred in relapsing disease and for patients wishing to preserve fertility.
- Membranous nephropathy: rituximab is now a first-line option (based on MENTOR trial); produces durable remissions with favorable toxicity vs. cyclosporine.
- Lupus nephritis: used in refractory disease.
- Steroid-dependent/resistant MCD and FSGS.
- Toxicities: infusion reactions, infection (PJP prophylaxis often co-prescribed), reactivation of hepatitis B, progressive multifocal leukoencephalopathy (rare).
7. Eculizumab (Anti-C5 Complement Inhibitor)
- Blocks terminal complement activation.
- Used in C3 glomerulopathy (C3GN, dense deposit disease) and atypical HUS-associated GN.
- Prior meningococcal vaccination (ideally ≥2 weeks before) and prophylactic antibiotics (penicillin V) are mandatory due to risk of encapsulated bacterial infections, especially Neisseria meningitidis.
8. Adrenocorticotrophic Hormone (ACTH / Tetracosactide)
- Repository corticotropin injection (Acthar Gel) stimulates adrenal steroid production but also has direct melanocortin receptor effects on podocytes.
- Used in membranous nephropathy and MCD, particularly in patients intolerant of other agents.
- Still an emerging option; evidence base is smaller than for other agents.
Disease-Specific Summary
| Disease | Induction | Maintenance |
|---|---|---|
| Minimal Change Disease | High-dose prednisone | Taper; CNI or MMF if steroid-dependent/resistant |
| FSGS | High-dose prednisone | CNI (tacrolimus); MMF |
| Membranous Nephropathy | Rituximab (1st line) or CNI + MMF | CNI or MMF |
| IgA Nephropathy | Steroids if proteinuria >1 g/day with progression; fish oil (omega-3) | ACEi/ARB (anti-proteinuric); budesonide (Nefecon) |
| Lupus Nephritis (III/IV) | MMF + steroids or IV cyclophosphamide + steroids | MMF or azathioprine + low-dose steroids |
| ANCA Vasculitis / Crescentic GN | Rituximab or CYC + high-dose steroids (± plasma exchange) | Azathioprine or rituximab |
| Anti-GBM Disease (Goodpasture) | CYC + high-dose steroids + plasma exchange | Short course immunosuppression |
| C3 Glomerulopathy | Eculizumab; MMF + steroids | Eculizumab |
Adjunctive Pharmacotherapy (All Forms)
- ACE inhibitors / ARBs: reduce proteinuria and slow progression in virtually all forms of GN — first-line background therapy.
- Statins: manage dyslipidemia (especially in nephrotic GN).
- Anticoagulation: consider in membranous nephropathy with serum albumin <2.5 g/dL (high thrombosis risk).
- PJP prophylaxis (trimethoprim-sulfamethoxazole): whenever high-dose steroids + another immunosuppressant are combined.
- Calcium/vitamin D + bisphosphonates: for steroid-induced osteoporosis.
Sources: Brenner and Rector's The Kidney, 2-Volume Set (chapters on GN treatment, ANCA vasculitis, fibrillary GN, membranous nephropathy); Harrison's Principles of Internal Medicine 22E; Murray & Nadel's Textbook of Respiratory Medicine
surgical interventional to this diease
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I now have detailed content on plasma exchange and renal replacement from Brenner and Rector's. I have enough to give a comprehensive answer.
Surgical/Interventional Treatments for Glomerulonephritis
Glomerulonephritis is primarily a medical disease, but several procedural and surgical interventions play important roles — particularly when immunosuppression is insufficient or when the kidneys fail.
1. Plasma Exchange (Plasmapheresis)
The most important acute intervention in GN.
Mechanism: Removes circulating pathogenic antibodies (anti-GBM antibodies, ANCA, immune complexes) and replaces plasma with fresh frozen plasma (FFP) or albumin.
Indications:
| Condition | Role |
|---|---|
| Anti-GBM Disease (Goodpasture syndrome) | Mandatory — removes anti-GBM IgG rapidly; combined with cyclophosphamide + steroids. Must be started urgently. Early plasmapheresis can recover renal function even in dialysis-dependent patients if initiated before 100% crescents on biopsy. |
| ANCA-associated crescentic GN | Used when presenting with dialysis dependence or severe pulmonary hemorrhage. Three RCTs showed no benefit over immunosuppression alone in patients not requiring dialysis (PEXIVAS trial confirmed this), but it remains an option in dialysis-dependent patients. |
| Rapidly Progressive GN (RPGN) | Adjunct in idiopathic crescentic GN, especially anti-GBM type. |
| MPGN / Cryoglobulinemic GN | Occasionally used in refractory cases. |
| Recurrent GN post-transplant (e.g., FSGS) | Plasmapheresis can reduce recurrence of primary FSGS in the allograft. |
Protocol: Typically 4-litre exchanges daily or alternate days for 2–3 weeks (10–14 sessions).
Risks: Bleeding (if FFP not used), hypocalcemia, infection, line complications (central venous access required).
2. Renal Biopsy
Not therapeutic but an essential diagnostic procedure that directly guides all treatment decisions.
- Percutaneous ultrasound-guided needle biopsy of the native kidney.
- Classifies GN type (e.g., crescentic, membranous, IgA, minimal change) and grades activity vs. chronicity.
- Performed under local anesthesia; major complications (significant bleeding requiring intervention) occur in ~1–2% of cases.
- Without biopsy, appropriate pharmacological or interventional therapy cannot be selected.
3. Renal Replacement Therapy (RRT)
When GN progresses to end-stage kidney disease (ESKD) or causes acute, severe kidney failure:
a. Haemodialysis (HD)
- Acute HD: Used as a bridge in severe RPGN/crescentic GN while awaiting immunosuppression to take effect.
- Chronic HD: Long-term option if GN leads to ESKD. Involves creation of an arteriovenous (AV) fistula or AV graft (surgical procedure) for vascular access, or tunnelled central venous catheter.
b. Peritoneal Dialysis (PD)
- An alternative to HD; a surgical tunnelled PD catheter is inserted into the peritoneal cavity.
- Less haemodynamically stressful; suitable for selected patients with GN-related ESKD.
4. Kidney Transplantation
The definitive surgical treatment for ESKD secondary to GN.
- Living donor (laparoscopic donor nephrectomy) or deceased donor transplant.
- Offers superior outcomes vs. long-term dialysis.
Disease-specific considerations:
| GN Type | Recurrence Risk in Allograft | Notes |
|---|---|---|
| Primary FSGS | 20–40% (high) | Recurs immediately post-transplant; plasmapheresis used prophylactically/therapeutically |
| IgA Nephropathy | ~50% histologically, but slow progression | Generally favourable graft survival |
| Membranous Nephropathy | ~30% | Monitor for recurrence with anti-PLA2R antibody levels |
| Anti-GBM Disease | Very low — but must wait ≥6–12 months post-remission and confirm anti-GBM antibody negativity before transplantation | |
| ANCA Vasculitis | Low recurrence | Monitor ANCA titres post-transplant |
| MPGN / C3 Glomerulopathy | High (especially C3GN with complement dysregulation) | Consider eculizumab peri-transplant |
| Lupus Nephritis | Rare — SLE tends to be quiescent post-transplant | Favourable outcomes |
Bilateral native nephrectomy is occasionally performed before transplant in patients with refractory hypertension, recurrent infections, or massive proteinuria from native kidneys.
5. Central Venous Access / Vascular Access Procedures
- Required for plasmapheresis (temporary HD catheter) and acute haemodialysis.
- AV fistula creation (surgical anastomosis of artery and vein, usually radiocephalic or brachiocephalic) is the gold standard for permanent HD access — preferred over grafts or catheters.
Key Principle
Glomerulonephritis has no direct surgical cure — all surgical interventions are either supportive (dialysis access, transplantation) or adjunctive (plasma exchange, biopsy). Immunosuppression remains the cornerstone of treatment, with procedural interventions reserved for acute crises, renal failure, or when pharmacological therapy has been exhausted.
Sources: Brenner and Rector's The Kidney, 2-Volume Set (ANCA vasculitis/crescentic GN treatment, plasma exchange, transplant recurrence); Robbins & Cotran Pathologic Basis of Disease; Harrison's Principles of Internal Medicine 22E
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