What is the initial treatment for Glomerulonephritis?

Initial Treatment of Glomerulonephritis

The initial treatment of glomerulonephritis depends entirely on the specific type diagnosed, as different forms require fundamentally different therapeutic approaches—ranging from supportive care alone for post-infectious GN to aggressive immunosuppression with corticosteroids plus cyclophosphamide or mycophenolate for lupus nephritis, or immediate plasmapheresis with cyclophosphamide for anti-GBM disease.

Treatment Algorithm by GN Type

Post-Infectious Glomerulonephritis (Post-Streptococcal)

• Antibiotic therapy: Administer penicillin (or erythromycin if penicillin-allergic) even when active infection is no longer present to decrease the streptococcal antigenic load 1, 2
• Supportive management is the cornerstone: Restrict dietary sodium to <2.0 g/day, use loop diuretics for fluid overload, and target blood pressure <130/80 mmHg 2
• Avoid routine immunosuppression: Corticosteroids should be considered ONLY for severe crescentic glomerulonephritis with rapidly progressive renal failure, based on anecdotal evidence 1, 2
• Critical distinction: Do NOT use corticosteroids for IgA-dominant post-infectious glomerulonephritis (typically staphylococcal, including MRSA), which occurs particularly in elderly and diabetic patients 1, 2

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)

For nephrotic syndrome presentation:

• First-line corticosteroid therapy: Prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose, or alternate-day dosing at 2 mg/kg (maximum 120 mg) 1
• Duration: Maintain high-dose therapy for a minimum of 4 weeks if complete remission is achieved, and for a maximum of 16 weeks if complete remission is not achieved 1
• Taper slowly: After achieving remission, taper corticosteroids over a total period of up to 6 months 1

Alternative first-line therapy (when corticosteroids contraindicated):

• Calcineurin inhibitors (CNIs): Consider as first-line therapy for patients with uncontrolled diabetes, psychiatric conditions, severe osteoporosis, or morbid obesity 1
• Cyclosporine preferred over tacrolimus in patients with strong family history of diabetes or elevated HbA1c due to lesser tendency to precipitate diabetes 1
• Dosing: Cyclosporine 3-5 mg/kg/day or tacrolimus 0.05-0.1 mg/kg/day in divided doses for 1-2 years 1

Steroid-resistant nephrotic syndrome (SRNS):

• Definition: Minimum of 8 weeks of adequate corticosteroid therapy required before declaring steroid resistance 1
• CNI as initial therapy: Use calcineurin inhibitors for a minimum of 6 months, continuing for at least 12 months if partial remission achieved by 6 months 1
• Combine with low-dose corticosteroids during CNI therapy 1

Lupus Nephritis (Class IV)

Initial aggressive immunosuppression is mandatory:

• Corticosteroids combined with either cyclophosphamide OR mycophenolate mofetil 1
• Both combinations have equivalent efficacy (1B evidence for each) 1
• Monitor closely: If worsening occurs (rising creatinine, worsening proteinuria) during first 3 months, change to alternative therapy or perform repeat biopsy 1

ANCA-Associated Vasculitis (Granulomatosis with Polyangiitis, Microscopic Polyangiitis)

Induction therapy for severe/organ-threatening disease:

• Cyclophosphamide plus corticosteroids is the standard initial approach 1
• Maintenance therapy required: After achieving remission, continue maintenance for at least 18 months with azathioprine 1-2 mg/kg/day as first choice 1
• Alternative maintenance: Mycophenolate mofetil up to 1 g twice daily for patients allergic to or intolerant of azathioprine 1

Resistant disease:

• Add rituximab if resistant to induction therapy with cyclophosphamide and corticosteroids 1

Anti-GBM Disease (Goodpasture Syndrome)

This is a medical emergency requiring immediate treatment:

• Triple therapy: Cyclophosphamide + corticosteroids + plasmapheresis 1
• Start treatment without delay once diagnosis is confirmed; if highly suspected, begin high-dose corticosteroids and plasmapheresis while awaiting confirmation 1
• Exception: Do not treat patients who are dialysis-dependent at presentation with 100% crescents on adequate biopsy and no pulmonary hemorrhage 1
• No maintenance therapy required after initial treatment 1

Membranoproliferative Glomerulonephritis (MPGN)

For children with nephrotic syndrome and/or impaired renal function:

• Alternate-day prednisone: 40 mg/m² on alternate days for 6-12 months (possibly longer if clear clinical response) 1
• Evidence: One randomized trial showed renal survival at 130 months of 61% with prednisone versus 12% with placebo (P=0.07) 3

Conservative approach for patients with:

• Normal eGFR and non-nephrotic-range proteinuria: Treat conservatively with renin-angiotensin-aldosterone system blockade and close monitoring 1

Universal Supportive Measures (All Types)

Regardless of specific GN type, initiate:

• Renin-angiotensin-aldosterone system inhibition: ACE inhibitors or ARBs for all patients with proteinuria 1
• Blood pressure control: Target <130/80 mmHg (or <125/75 mmHg if proteinuria >1 g/day) 2
• Sodium restriction: <2.0 g/day 2
• Loop diuretics: For managing fluid overload and edema 2, 4
• Statin therapy: For hyperlipidemia associated with nephrotic syndrome 1

Critical Pitfalls to Avoid

• Do not delay biopsy: Specific diagnosis is essential because treatment differs dramatically between GN types 1
• Do not declare steroid resistance prematurely: Requires minimum 8 weeks of adequate therapy 1, 4
• Do not use corticosteroids for IgA-dominant post-infectious GN: This variant (associated with staphylococcal infections) should NOT receive immunosuppression 1, 2
• Do not delay anti-GBM treatment: This is a medical emergency; start treatment immediately upon strong clinical suspicion 1
• Do not stop therapy prematurely: If partial response is occurring, continue up to 16 weeks for MCD/FSGS 1, 4

Monitoring Treatment Response

• Complete remission defined as: Urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 4
• Monitor daily: Urine protein using dipstick or spot urine protein-to-creatinine ratio 4
• For post-infectious GN: C3 complement should normalize within 8-12 weeks; if not, perform kidney biopsy to exclude C3 glomerulonephritis 2