SUN-027 TACROLIMUS WITH ORAL PREDNISOLONE VERSUS CYCLICAL CYCLOPHOSPHAMIDE AND STEROIDS IN PRIMARY MEMBRANOUS NEPHROPATHY: 5-YEAR OUTCOME OF THE RANDOMISED TRIAL

Abstract

KDIGO recommends Cyclical cyclophosphamide/steroids (cCTX/GC) and calcineurin inhibitors (tacrolimus or cyclosporine)/steroids as the 1st line agent in the management of antiproteinuric resistant primary membranous nephropathy (PMN). Long-term outcome of cCTX/GC is available. However, the long-term outcome of patients treated with tacrolimus/steroids (TAC/GC) is not known. We report the 5-year outcome of patients who were randomised to receive cCTX/GC or TAC/GC. Seventy patients were randomised in 1:1 ratio to receive either cCTX/GC or TAC/GC for antiproteinuric resistant PMN. The study was designed to observe primary outcome of remission at 12 months, 71 and 77% of the patients in the TAC/GC and cCTX/GC achieved remission respectively. In the present abstract we report the 5-year outcome of the same patients enrolled in the randomised controlled trial. Patients were followed on a monthly basis for 12 months, then quarterly till 24 months and then 6-monthly till completion of 5 years. Definition: Complete remission (CR) Proteinuria <500 mg/day with normal serum albumin (≥3.5 g/dL) and serum creatinine. Partial remission (PR): Proteinuria ≥500 mg/day, but <2 g/day or <50% of baseline with normal serum albumin (≥3.5 g/dL) and serum creatinine. Relapse: Nephrotic syndrome (proteinuria >3.5 g/day or >2.5 g/day with serum albumin <2.5 g/dL) after any CR or PR. Persistent remission: maintenance of remission without any need for further immunosuppression. Relapse was treated as per the discretion of the treating Nephrologist. . At the end of 12 months, three patients were lost to follow-up, all the 67 patients continued there follow-up. At the end of 60 months, 32 (94.1%) and 20 (60.6%) patients were in remission in the cCTX/GC and TAC/GC group, respectively (p=0.001). Eighteen (53%) and fourteen (41.1%) patients had CR and PR with cCTX/GC as the initial therapy, respectively. Twelve (36.4%) and eight (24.2%) patients had CR and PR with TAC/GC as the initial therapy, respectively Five (14.7%) and 18 (54.5%) patients had a relapse at 60 months in cCTX/GC and TAC/GC group, respectively (p<0.05). Persistent remission was observed in 26 (74.2%) and 10 (28.6%) patients respectively (p<0.001). There was an association of anti-PLA2R with relapse (p<0.05). Doubling of serum creatinine/dialysis requirement or death was reported in 1 (2.9%) and 04 (12.1%) patients in the cCTX/GC and TAC/GC group respectively (p>0.05). None of the patients treated with cCTX/GC reported with any solid organ or haematological malignancies. All the female patients >40 years prior to treatment with cCTX/GC had amenorrhea at the last follow-up. At the end of 60 months of randomisation, relapse rates are higher in TAC/GC treated patients. Hence, in the long-term cCTX/GC is better than TAC/GC as 1st line therapy for the management of antiproteinuric resistant primary membranous nephropathy.