Idiopathic Membranous Nephropathy: Outline and Rationale of a Treatment Strategy

Outline of proposed treatment strategy in patients with IMN.

Outcome in studies of patients with IMN is dependent on the prevalence of nephrotic syndrome. Relation of the calculated percentage of patients with progressive renal insufficiency during 5-year follow-up and the percentage of patients with nephrotic syndrome in studies of membranous nephropathy.

Renal survival in patients with IMN and renal insufficiency treated with alkylating agents (treated) compared with historic controls (controls). Data adapted from du Buf-Vereijken et al⁸ (cyclophosphamide; straight lines) and Torres et al⁹ (chlorambucil; dotted lines). Data from Torres et al⁹ were recalculated to provide overall renal survival without censoring for death.

Renal survival in patients with IMN, nephrotic syndrome, and normal renal function using a restrictive treatment policy.¹⁶ Overall, 48% of patients needed immunosuppressive treatment during follow-up. For comparison, renal survival is shown for patients included in the RCT of Ponticelli et al³ comparing chlorambucil and steroids (treated) with no treatment (untreated).

Efficacy of MMF in patients with IMN. Serum creatinine levels at baseline and after 6 months are shown as reported by Miller et al⁸¹ (dotted lines) and du Buf-Vereijken and Wetzels¹⁰⁰ (straight lines). Differences are significant, likely explained by the greater dose of MMF, longer duration of therapy, and concomitant use of prednisone in all patients in the latter study. To convert creatinine in mg/dL to μmol/L, multiply by 88.4.

Urinary β2M excretion and serum albumin level predict renal survival in patients with IMN, nephrotic syndrome, and normal renal function at biopsy. Data adapted from Branten et al.¹⁸ Threshold values were 0.5 μg/min for urinary β2M and 2.2 g/dL (22 g/L) for serum albumin.