Treatment Approach for Glomerulonephritis

General Treatment Principles

• 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, 2
• 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 2

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 2, 3
• Target systolic blood pressure <120 mmHg in most adult patients using standardized office BP measurement 2, 3
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory blood pressure monitoring 2
• Hold RAS inhibitors during intercurrent illnesses with risk of volume depletion 3

Edema Management

• Use diuretics as first-line agents for edema management 2
• Add mechanistically different diuretics if response is insufficient 2
• Monitor for adverse effects of diuretics including hyponatremia, hypokalemia, GFR reduction, and volume depletion 2

Dietary Management

• Adjust protein intake based on degree of proteinuria and kidney function 3
• For nephrotic-range proteinuria: 0.8-1 g/kg/day with additional protein to compensate for losses (up to 5 g/day) 3
• For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day 3
• Avoid protein restriction <0.6 g/kg/day due to safety concerns and risk of malnutrition 4

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 5
• Manage nephritic syndrome with diuretics, antihypertensives, supportive care, and dialysis if necessary 5
• For severe crescentic post-streptococcal GN, consider corticosteroids based on anecdotal evidence 5
• For infective endocarditis-related GN: continue antibiotic treatment for 4-6 weeks, although hematuria, proteinuria, and azotemia may not resolve for months 5

Membranous Nephropathy

• Consider observation for 6 months before initiating immunosuppressive therapy unless there are severe symptoms or declining kidney function 3
• 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) 3
• Consider cyclosporine or tacrolimus for at least 6 months in patients with contraindications to cyclical corticosteroid/alkylating-agent regimens 3

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 3
• Taper corticosteroids slowly over 6 months after achieving complete remission 3
• For steroid-resistant or steroid-intolerant cases, consider calcineurin inhibitors (cyclosporine or tacrolimus) 3

Membranoproliferative Glomerulonephritis (MPGN)

• Consider immunosuppressive therapy for nephrotic syndrome with or without progressive decline in kidney function, active nephritic syndrome, or rapidly progressive disease 6
• 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 6
• Patients with normal eGFR and non-nephrotic-range proteinuria may be treated conservatively 6
• Avoid immunosuppression in patients with advanced CKD, severe tubulointerstitial fibrosis, small kidney size, or other findings consistent with chronic inactive disease 6

Immunosuppression Safety Considerations

• Screen for latent infections prior to initiating immunosuppression 3
• Monitor therapeutic drug levels where clinically indicated 3
• Review vaccination status and update as required before starting immunosuppression 3
• Consider fertility preservation where indicated 3
• Monitor for development of cancers or infections during immunosuppressive therapy 3
• Provide pneumococcal vaccine, influenza vaccine, and herpes zoster vaccination (Shingrix) 3
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 3

Monitoring and Follow-up

• Assess proteinuria regularly - reduction in proteinuria is a marker of treatment response 3, 4
• Monitor for a ≥40% decline in eGFR from baseline over 2-3 years as a surrogate outcome measure for kidney failure 3
• Perform repeat kidney biopsy only if the patient has rapidly deteriorating kidney function or if it will potentially alter the diagnosis or therapeutic plan 3, 4

Common Pitfalls and Caveats

• IgA-dominant postinfectious GN needs to be distinguished from idiopathic IgA nephropathy and HSP to avoid inappropriate corticosteroid treatment 5
• 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 4

Glomerulonephritis Treatment Approaches

Disease-Specific Treatment Approaches

• For HCV-infected patients with CKD Stages 1 or 2 and GN, the American Journal of Kidney Diseases recommends using combined antiviral treatment with pegylated interferon and ribavirin 7, 8
• For HCV-infected patients with CKD Stages 3, 4, or 5 and GN not yet on dialysis, the American Journal of Kidney Diseases recommends using monotherapy with pegylated interferon, with doses adjusted to kidney function 7, 8
• For HBV infection and GN, the American Journal of Kidney Diseases recommends treating with interferon-α or nucleoside analogues as recommended for the general population 7, 8
• For adults or children with presumed idiopathic MPGN with nephrotic syndrome AND progressive decline of kidney function, the American Journal of Kidney Diseases recommends using oral cyclophosphamide or MMF plus low-dose alternate-day or daily corticosteroids with initial therapy limited to less than 6 months 7, 8
• The American Journal of Kidney Diseases notes that the term MPGN is being replaced with a mechanistic classification based on complement (Ig+C3 and Ig-C3) 7, 8
• For MPGN, the American Journal of Kidney Diseases recommends that treatment should be based on identification of the underlying cause and may include immunosuppression, chemotherapy for monoclonal gammopathy disorders, or complement-regulatory therapies 7, 8

Management of Membranoproliferative Glomerulonephritis and Other Forms of Glomerulonephritis

Disease-Specific Treatment Approaches

• For adults or children with presumed idiopathic Membranoproliferative Glomerulonephritis (MPGN) with nephrotic syndrome AND progressive decline of kidney function, the American Journal of Kidney Diseases recommends using oral cyclophosphamide or MMF plus low-dose alternate-day or daily corticosteroids with initial therapy limited to less than 6 months 9
• The American Journal of Kidney Diseases suggests that the term MPGN is being replaced with a mechanistic classification based on complement (Ig+C3 and Ig-C3) 9
• For Minimal Change Disease (MCD), the American Journal of Kidney Diseases recommends using high-dose corticosteroids for initial treatment, tapered over a period of 4 weeks if complete remission is achieved, and for a maximum period of 16 weeks if complete remission is not achieved 10
• For patients with contraindications or intolerance to high-dose corticosteroids, the American Journal of Kidney Diseases suggests using oral cyclophosphamide or calcineurin inhibitors 10
• For HCV-infected patients with CKD Stages 1 or 2 and GN, the American Journal of Kidney Diseases recommends using combined antiviral treatment with pegylated interferon and ribavirin 9
• Vigilant monitoring for side effects is warranted, irrespective of chosen therapy, with supportive care aimed at limiting ancillary damage from both nephrotic syndrome and immunosuppressive agents 11, 10