Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy

INTRODUCTION: Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known. METHODS: We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system–resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years. RESULTS: At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy. CONCLUSIONS: To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN.