What is the treatment for glomerulonephritis (inflammation of the glomeruli in the kidneys)?

Treatment of Glomerulonephritis

Treatment of glomerulonephritis requires a disease-specific approach combining supportive care measures (ACE inhibitors/ARBs, blood pressure control, dietary management) with targeted immunosuppression based on the specific type of glomerulonephritis, disease severity, and patient characteristics. 1

Initial Diagnostic and Treatment Framework

• Obtain a kidney biopsy as the gold standard for diagnosis—this guides specific treatment selection and determines whether immunosuppression is warranted 1
• Classify the glomerulonephritis mechanistically (immune-complex mediated, pauci-immune, anti-GBM, complement-mediated, or monoclonal immunoglobulin-associated) rather than by histologic pattern alone 2
• Tailor treatment intensity based on presenting symptom severity, specific glomerulonephritis type, and risk of progression 1

Universal Supportive Care Measures (All Types)

Blood Pressure and Proteinuria Management

• Use ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for all patients with hypertension and proteinuria 1
• Target systolic blood pressure <120 mmHg in most adults using standardized office BP measurement 1
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory monitoring 1
• Hold RAS inhibitors during intercurrent illnesses with volume depletion risk 1

Edema and Fluid Management

• Use diuretics as first-line agents for edema management 1
• Add mechanistically different diuretics if response is insufficient 1
• Monitor for hyponatremia, hypokalemia, GFR reduction, and volume depletion 1

Dietary Management

• For nephrotic-range proteinuria: 0.8-1 g/kg/day protein with additional protein to compensate for losses (up to 5 g/day) 1
• For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day 1
• Avoid protein restriction <0.6 g/kg/day due to malnutrition risk 1
• Restrict sodium to <2.0 g/day to control hypertension and fluid retention 3

Disease-Specific Immunosuppressive Approaches

IgA Nephropathy (High-Risk Patients)

• For patients with proteinuria >1 g/day despite ≥3 months of optimized supportive care (maximally tolerated ACE inhibitor/ARB and BP control) AND eGFR ≥30 ml/min/1.73 m²: consider glucocorticoids after individualized risk-benefit discussion 4
• Do NOT use mycophenolate mofetil in non-Chinese patients; it may be used as a glucocorticoid-sparing agent in Chinese patients only 4
• Consider tonsillectomy in Japanese patients only (insufficient data for non-Japanese patients) 4
• For rapidly progressive IgAN with extensive crescent formation (>50% of glomeruli): treat with cyclophosphamide and glucocorticoids per ANCA-associated vasculitis protocols 4
• Assess toxicity risk factors before glucocorticoids: advanced age, metabolic syndrome, obesity, latent infections (TB, HIV, HBV, HCV) 4

Post-Infectious Glomerulonephritis

• Administer penicillin (or erythromycin if penicillin-allergic) even in the absence of persistent infection to decrease antigenic load 1, 3
• First-generation cephalosporins (cephalexin) are appropriate alternatives for non-anaphylactic penicillin allergies 3
• Third-generation cephalosporins (ceftriaxone) for severe infections or resistant organisms 3
• Manage nephritic syndrome with diuretics, antihypertensives, and supportive care 1
• For severe crescentic post-streptococcal GN: consider corticosteroids based on anecdotal evidence only 1, 3
• Do NOT use corticosteroids for IgA-dominant post-infectious GN (typically staphylococcal, including MRSA) 3
• For infective endocarditis-related GN: continue antibiotics for 4-6 weeks (hematuria/proteinuria may persist for months) 1

Membranous Nephropathy

• Consider observation for 6 months before initiating immunosuppression unless severe symptoms or declining kidney function are present 1
• For patients requiring immunosuppression: use 6-month course of alternating monthly cycles of oral and IV corticosteroids with oral cyclophosphamide (preferred over chlorambucil) 1
• Consider cyclosporine or tacrolimus for ≥6 months in patients with contraindications to cyclical corticosteroid/alkylating-agent regimens 1

Focal Segmental Glomerulosclerosis (FSGS)

• For nephrotic syndrome due to FSGS: use high-dose corticosteroids for minimum 4 weeks, up to maximum 16 weeks as tolerated or until complete remission 4, 1
• Taper corticosteroids slowly over 6 months after achieving complete remission 4, 1
• For steroid-resistant or steroid-intolerant cases: use calcineurin inhibitors (cyclosporine or tacrolimus) 1

Membranoproliferative Glomerulonephritis (MPGN)

• For nephrotic syndrome with progressive decline in kidney function, active nephritic syndrome, or rapidly progressive disease: use oral cyclophosphamide or MMF plus low-dose alternate-day or daily corticosteroids for <6 months 1
• For children with MPGN and nephrotic syndrome and/or impaired renal function: consider alternate-day steroids (40 mg/m²) for 6-12 months 1
• Patients with normal eGFR and non-nephrotic-range proteinuria may be treated conservatively 1
• Avoid immunosuppression in patients with advanced CKD, severe tubulointerstitial fibrosis, small kidney size, or chronic inactive disease 1

Minimal Change Disease (MCD)

• IgA nephropathy with mesangial IgA deposition and histologic features of MCD should be treated according to MCD guidelines, not IgAN protocols 4
• Use high-dose corticosteroids for initial treatment, tapered over 4 weeks if complete remission achieved, maximum 16 weeks if not 1
• For contraindications or intolerance to high-dose corticosteroids: use oral cyclophosphamide or calcineurin inhibitors 1

Infection-Associated Glomerulonephritis

• For HCV-infected patients with CKD Stages 1-2 and GN: use combined pegylated interferon and ribavirin 1
• For HCV-infected patients with CKD Stages 3-5 (not on dialysis) and GN: use monotherapy with pegylated interferon, doses adjusted to kidney function 1
• For HBV infection and GN: treat with interferon-α or nucleoside analogues per general population recommendations 1

Immunosuppression Safety Protocol

Pre-Treatment Screening

• Screen for latent infections (TB, HIV, HBV, HCV) prior to initiating immunosuppression 1
• Review and update vaccination status before starting immunosuppression 1
• Provide pneumococcal vaccine, influenza vaccine, and herpes zoster vaccination (Shingrix) 1
• Consider fertility preservation where indicated 1

Prophylaxis and Monitoring

• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 1
• Monitor therapeutic drug levels where clinically indicated 1
• Monitor for development of cancers or infections during immunosuppressive therapy 1

Monitoring and Treatment Response

• Assess proteinuria regularly—reduction in proteinuria is the primary marker of treatment response 1
• Monitor for ≥40% decline in eGFR from baseline over 2-3 years as surrogate outcome for kidney failure 1
• For post-streptococcal GN: C3 complement should normalize within 8-12 weeks; if persistently low beyond 12 weeks, perform kidney biopsy to exclude C3 glomerulonephritis 5, 3
• Perform repeat kidney biopsy only if rapidly deteriorating kidney function or if it will potentially alter diagnosis or therapeutic plan 1

Critical Pitfalls to Avoid

• Do not confuse IgA-dominant postinfectious GN with idiopathic IgA nephropathy—the former should NOT receive corticosteroids 1, 3
• Do not use glucocorticoids in IgAN patients with eGFR <30 ml/min/1.73 m² due to unfavorable risk-benefit ratio 4
• Avoid prolonged or multiple rounds of immunosuppression due to cumulative toxic drug exposure 1
• Do not extrapolate pediatric treatment data directly to adults—adults respond more slowly and variably to steroids with higher risk of side effects 4
• Recognize that patients with advanced CKD, severe tubulointerstitial fibrosis, or chronic inactive disease should receive supportive care only, not immunosuppression 1