Early versus late start of immunosuppressive therapy in idiopathic membranous nephropathy : a randomized controlled trial

Background. Immunosuppressive therapy in idiopathic membranous nephropathy (iMN) is debated. Accurate identification of patients at high risk for end-stage renal disease (ESRD) allows early start of therapy in these patients. It is unknown if early start of therapy is more effective and/or less toxic than late start (i.e. when GFR deteriorates). Methods. We conducted a randomized open-label study in patients with iMN, a normal renal function and a high risk for ESRD (urinary β2m >0.5 μg/min, UIgG >125 mg/ day). Patients started with immunosuppressive therapy (cyclophosphamide for 12 months, and steroids) either immediately after randomization or when renal function deteriorated ( sCr ≥+25% and sCr >135 μmol/l or sCr ≥+50%). End points were remission rates, duration of the nephrotic syndrome (NS), renal function and complications. Results. The study included 26 patients (24 M/2 F), age 48 ± 12 years; sCr 96 μmol/l (range 68–126) and median proteinuria 10.0 g/10 mmol Cr. Early treatment resulted in a more rapid onset of remission (P = 0.003) and a shorter duration of the NS (P = 0.009). However, at the end of the follow-up (72 ± 22 m), there were no differences in overall remission rate, sCr (93 versus 105 μmol/l), proteinuria, relapse rate and adverse events. Conclusions. In high-risk patients with iMN, immunosuppressive treatment is effective in inducing a remission. Early treatment shortens the duration of the nephrotic phase, but does not result in better preservation of renal function. Our study indicates that treatment decisions must be based on risk and benefit assessment in the individual patient.