Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy
Raja Ramachandran, Vinod Kumar, Joyita Bharati, Brad H. Rovin, Ritambhra Nada, Vivek Kumar, Manish Rathi, Vivekanand Jha, Krishan Lal Gupta, Harbir Singh Kohli
Abstract
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.