What is the treatment plan for glomerulonephritis according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines?

Glomerulonephritis and KDIGO Treatment Guidelines

Glomerulonephritis is inflammation of the glomeruli, the filtering units of the kidneys, requiring disease-specific treatment approaches based on the underlying cause, severity, and patient characteristics according to KDIGO guidelines.

Definition and Pathophysiology

• Glomerulonephritis (GN) refers to inflammation of the glomeruli, which are the filtering units of the kidneys, leading to hematuria, proteinuria, and potentially declining kidney function 1
• Diagnosis requires kidney biopsy as the gold standard to determine the specific type of glomerulonephritis and guide appropriate treatment 1, 2
• Glomerulonephritis can present as acute nephritis, nephrotic syndrome, or with minor proteinuria or hematuria 3

General Treatment Principles

• Treatment should address both the underlying cause and kidney manifestations, with therapy tailored to the specific type of glomerulonephritis, disease severity, and patient characteristics 1
• Choose treatment regimens that address immediate disease morbidity, with intensity of induction therapy based on presenting symptom severity 1
• Select therapy that prevents disease progression, recognizing that complete clinical remission may not be possible in all forms of chronic glomerulonephritis 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, 4
• Target systolic blood pressure <120 mmHg in most adult patients using standardized office BP measurement 1, 4
• 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

Edema Management

• Restrict dietary sodium to <2.0 g/day to reduce edema, control blood pressure, and help manage proteinuria 4, 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 1
• For nephrotic-range proteinuria: 0.8-1 g/kg/day 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 safety concerns and risk of malnutrition 1, 2

Disease-Specific Treatment Approaches

Infection-Related Glomerulonephritis

• For HCV-infected patients with CKD Stages 1 or 2 and GN, use combined antiviral treatment with pegylated interferon and ribavirin 5
• 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 5
• For HBV infection and GN, treat with interferon-α or nucleoside analogues as recommended for the general population 5

Membranoproliferative Glomerulonephritis (MPGN)

• For adults or children with 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 5
• The term MPGN is being replaced with a mechanistic classification based on complement (Ig+C3 and Ig-C3) 5
• Treatment should be based on identification of the underlying cause and may include immunosuppression, chemotherapy for monoclonal gammopathy disorders, or complement-regulatory therapies 5

Membranous Nephropathy

• Consider observation for 6 months before initiating immunosuppressive therapy unless there are severe symptoms or declining kidney function 1, 4
• 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, 4
• Consider cyclosporine or tacrolimus for at least 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 a minimum of 4 weeks, up to 16 weeks as tolerated 1, 4
• 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

Immunosuppression Safety Considerations

• Screen for latent infections prior to initiating immunosuppression 1, 4
• Monitor therapeutic drug levels where clinically indicated 1, 4
• Review vaccination status and update as required before starting immunosuppression 1, 4
• Consider fertility preservation where indicated 1
• Monitor for development of cancers or infections during immunosuppressive therapy 1
• Provide pneumococcal vaccine, influenza vaccine, and herpes zoster vaccination (Shingrix) 1, 4
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 1, 4

Monitoring and Follow-up

• Assess proteinuria regularly - reduction in proteinuria is a marker of treatment response 1, 4
• Monitor for a ≥40% decline in eGFR from baseline over 2-3 years as a surrogate outcome measure for kidney failure 1, 4
• Perform repeat kidney biopsy only if the patient has rapidly deteriorating kidney function or if it will potentially alter the diagnosis or therapeutic plan 1, 2

Common Pitfalls and Caveats

• IgA-dominant postinfectious GN needs to be distinguished from idiopathic IgA nephropathy 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 1, 2
• Avoid immunosuppression in patients with advanced CKD, severe tubulointerstitial fibrosis, small kidney size, or other findings consistent with chronic inactive disease 1