What is the treatment approach for Glomerulonephritis (inflammation of the glomeruli)?

Treatment Approach for Glomerulonephritis

The treatment of glomerulonephritis requires a disease-specific approach that addresses both the underlying cause and kidney manifestations, with therapy tailored to the specific type of glomerulonephritis, disease severity, and patient characteristics. 1

General Treatment Principles

• Choose a treatment regimen that addresses immediate disease morbidity, with intensity of induction therapy based on presenting symptom severity and glomerulonephritis type 1
• Select therapy that prevents disease progression, recognizing that complete clinical remission may not be possible in all forms of chronic glomerulonephritis 1
• Minimize harmful side effects from immunosuppression through careful monitoring and prophylactic measures 1
• Kidney biopsy remains the gold standard for diagnosis and guides specific treatment selection 1

Supportive Care Measures

Blood Pressure and Proteinuria Management

• Use ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for patients with both hypertension and proteinuria 1, 2
• Target systolic blood pressure <120 mmHg in most adult patients using standardized office BP measurement 1, 2
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory blood pressure monitoring 1
• Hold RAS inhibitors during intercurrent illnesses with risk of volume depletion 2

Edema Management

• Restrict dietary sodium to <2.0 g/day to reduce edema, control blood pressure, and manage proteinuria 2
• Use diuretics as first-line agents for edema management 1
• Add mechanistically different diuretics if response is insufficient 1
• Monitor for adverse effects of diuretics including hyponatremia, hypokalemia, GFR reduction, and volume depletion 1

Dietary Management

• Adjust protein intake based on degree of proteinuria and kidney function 2:
  • For nephrotic-range proteinuria: 0.8-1 g/kg/day with additional protein to compensate for losses (up to 5 g/day) 2
  • For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day 2
• Avoid protein restriction <0.6 g/kg/day due to safety concerns and risk of malnutrition 3

Disease-Specific Treatment Approaches

Infection-Related Glomerulonephritis

• For post-streptococcal GN: treat with penicillin (or erythromycin if penicillin-allergic) even in absence of persistent infection 1
• Manage nephritic syndrome with diuretics, antihypertensives, supportive care, and dialysis if necessary 1
• For severe crescentic post-streptococcal GN, consider corticosteroids based on anecdotal evidence 1
• For infective endocarditis-related GN: continue antibiotic treatment for 4-6 weeks, although hematuria, proteinuria, and azotemia may not resolve for months 1

Membranous Nephropathy

• Consider observation for 6 months before initiating immunosuppressive therapy unless there are severe symptoms or declining kidney function 2
• For patients requiring immunosuppression, use a 6-month course of alternating monthly cycles of oral and IV corticosteroids with oral alkylating agents (cyclophosphamide preferred over chlorambucil) 2
• Consider cyclosporine or tacrolimus for at least 6 months in patients with contraindications to cyclical corticosteroid/alkylating-agent regimens 2

Focal Segmental Glomerulosclerosis (FSGS)

• For nephrotic syndrome due to FSGS, consider high-dose corticosteroids for a minimum of 4 weeks, up to 16 weeks as tolerated 2
• Taper corticosteroids slowly over 6 months after achieving complete remission 2
• For steroid-resistant or steroid-intolerant cases, consider calcineurin inhibitors (cyclosporine or tacrolimus) 2

Membranoproliferative Glomerulonephritis (MPGN)

• Consider immunosuppressive therapy for nephrotic syndrome with or without progressive decline in kidney function, active nephritic syndrome, or rapidly progressive disease 1
• For children with MPGN and nephrotic syndrome and/or impaired renal function, consider a trial of 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 other findings consistent with chronic inactive disease 1

Rapidly Progressive Glomerulonephritis (RPGN)

• Standard treatment includes glucocorticoids, cyclophosphamide, or rituximab 4
• Plasma exchange is especially important for anti-glomerular basement membrane disease and select cases of ANCA-associated vasculitis 4
• Early diagnosis and prompt treatment are critical to prevent progression to end-stage renal disease 4

Immunosuppression Safety Considerations

• Screen for latent infections prior to initiating immunosuppression 2
• Monitor therapeutic drug levels where clinically indicated 2
• Review vaccination status and update as required before starting immunosuppression 2
• Consider fertility preservation where indicated 2
• Monitor for development of cancers or infections during immunosuppressive therapy 2
• Provide pneumococcal vaccine, influenza vaccine, and herpes zoster vaccination (Shingrix) 2
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 2

Monitoring and Follow-up

• Assess proteinuria regularly - reduction in proteinuria is a marker of treatment response 2, 3
• Monitor for a ≥40% decline in eGFR from baseline over 2-3 years as a surrogate outcome measure for kidney failure 2
• Perform repeat kidney biopsy only if the patient has rapidly deteriorating kidney function or if it will potentially alter the diagnosis or therapeutic plan 2, 3

Common Pitfalls and Caveats

• Avoid delaying treatment in rapidly progressive forms of glomerulonephritis 4
• IgA-dominant postinfectious GN needs to be distinguished from idiopathic IgA nephropathy and HSP to avoid inappropriate corticosteroid treatment 1
• Prolonged immunosuppression or multiple rounds of immunosuppression is associated with more toxic drug exposure over time 1
• The safety of protein restriction in glomerulonephritis has not been established in children 3