What is the treatment for glomerulonephritis?

Treatment of Glomerulonephritis

The treatment of glomerulonephritis requires a targeted approach based on the specific type of glomerular disease, with supportive care including blood pressure control with ACE inhibitors or ARBs forming the foundation of management, while immunosuppressive therapy is reserved for specific cases with severe or progressive disease. 1, 2

General Management Principles

Supportive Care

• Restrict dietary sodium to <2.0 g/day to reduce edema, control blood pressure, and help manage proteinuria 1, 2
• Use diuretics as first-line agents for edema management, adding mechanistically different diuretics if response is insufficient 1
• Monitor for adverse effects of diuretics including hyponatremia, hypokalemia, GFR reduction, and volume depletion 1
• Adjust protein intake based on degree of proteinuria and kidney function:
  • For nephrotic-range proteinuria: 0.8-1 g/kg/day with additional protein to compensate for losses 1
  • For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day 1

Blood Pressure Management

• Use ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for patients with both hypertension and proteinuria 1, 3
• Target systolic blood pressure <120 mmHg in most adult patients using standardized office BP measurement 1
• 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 1

Disease-Specific Treatment Approaches

Membranous Nephropathy

• Consider observation for 6 months before initiating immunosuppressive therapy unless there are severe symptoms or declining kidney function 1
• 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) 1
• Adjust doses of cyclophosphamide or chlorambucil according to patient age and eGFR 1
• Consider cyclosporine or tacrolimus for at least 6 months in patients who cannot receive cyclical corticosteroid/alkylating-agent regimens 1

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 1
• Taper corticosteroids slowly over 6 months after achieving complete remission 1
• For steroid-resistant or steroid-intolerant cases, consider calcineurin inhibitors (cyclosporine or tacrolimus) 1

Lupus Nephritis

• Initial therapy should include corticosteroids combined with either cyclophosphamide or mycophenolate mofetil (MMF) 4
• If worsening lupus nephritis occurs during the first 3 months of treatment, change to an alternative recommended therapy or perform a repeat kidney biopsy 4
• For pure class V lupus nephritis with persistent nephrotic proteinuria, treat with corticosteroids plus an additional immunosuppressive agent: cyclophosphamide, calcineurin inhibitor, MMF, or azathioprine 4
• For relapse after complete or partial remission, use the initial therapy that was effective in inducing the original remission 4

Membranoproliferative Glomerulonephritis (MPGN)

• For presumed idiopathic MPGN with nephrotic syndrome AND progressive decline of kidney function, use oral cyclophosphamide or MMF plus low-dose alternate-day or daily corticosteroids with initial therapy limited to less than 6 months 4
• The key to optimal treatment of MPGN depends on identification of the underlying cause and may include immunosuppression, chemotherapy of monoclonal gammopathy disorders, or complement-regulatory therapies 4

Infection-Related Glomerulonephritis

• For HCV-infected patients with CKD Stages 1 or 2 and GN, use combined antiviral treatment with pegylated interferon and ribavirin 4
• For HCV-infected patients with CKD Stages 3,4, or 5 and GN not yet on dialysis, use monotherapy with pegylated interferon, with doses adjusted to kidney function 4
• For HBV infection and GN, treat with interferon-alfa or nucleoside analogues (tenofovir or entecavir preferred in Canada) 4
• For tuberculosis-related glomerulonephritis, use standard anti-tuberculosis therapy plus corticosteroids 5

Rapidly Progressive Glomerulonephritis (RPGN)

• Treat aggressively and as early as possible to prevent chronic renal failure 6, 7
• Traditional treatment relies on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions 6

Monitoring and Follow-up

• Assess proteinuria regularly - reduction in proteinuria is a marker of treatment response 1, 2
• Monitor for a ≥40% decline in eGFR from baseline over 2-3 years as a surrogate outcome measure for kidney failure 1, 2
• Perform repeat kidney biopsy only if the patient has rapidly deteriorating kidney function (doubling of serum creatinine over 1-2 months) 1

Infection Prevention

• Administer pneumococcal vaccine to patients with glomerular disease and nephrotic syndrome 1
• Ensure patients and household contacts receive influenza vaccine 1
• Provide herpes zoster vaccination (Shingrix) 1
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 1
• Screen for tuberculosis, hepatitis B, hepatitis C, HIV, and syphilis in clinically appropriate patients 1

Common Pitfalls and Caveats

• Avoid protein restriction <0.6 g/kg/day due to safety concerns and risk of malnutrition 2
• The safety of protein restriction in glomerulonephritis has not been established in children 2
• Screen for latent infections prior to initiating immunosuppression 1, 2
• Monitor therapeutic drug levels where clinically indicated 1, 2
• Review vaccination status and update as required before starting immunosuppression 1, 2
• Consider fertility preservation where indicated for patients receiving cyclophosphamide 1
• Monitor for development of cancers or infections during immunosuppressive therapy 1, 2