Is Late Conversion To Everolimus Beneficial in Kidney Transplant Patients With Interstitial Fibrosis Tubular Atrophy?

Abstract

Introduction: Interstitial fibrosis & tubular atrophy is the leading cause of graft loss in kidney transplant patient. Proliferation signal inhibitors may help in reducing calcineurin inhibitor exposure without increasing acute rejection episodes. Current study evaluated efficacy of conversion from mycophenolate to everolimus with CNI minimization in patients with biopsy proven IFTA and deteriorating renal function. Methods: Prospective single center trial, study cohort selected from 200 live related renal transplant recipients in followup. All had received basiliximab induction and triple drug immunosupression (tacrolimus, MMF/EC-MFS, steroids). Inclusion criteria: biopsy proven IFTA, absence of significance proteinuria (<400 mg/24 hour), progressive graft dysfunction (decline of GFR > 15% over 1 month), eGFR>40ml/min/1.73m2. All underwent conversion from mycophenolate to everolimus with CNI minimization. Results: The study group composed of 22 patients (M:F=19:3), mean age 37 years (range 24-58). Conversion done at 24 months (range: 3-112 months) post-transplantation and median follow-up is 22 (IQR: 5-9) months. Of these 23 patients, only 2 had an early conversion and the rest 21 had a late conversion. The tacrolimus trough levels decreased from 5.1 ± 1.6 ng/ml to 3.6 ± 1.1 ng/ml (p=0.03). The everolimus levels achieved were 6.68 ± 2.4 ng/ml and 5.7±1.4 ng/ml at 1 and 3 months. The eGFR that had declined from best stable values of 59.3± 11.9ml/min to 48.2±9.5ml/min at conversion stabilized and improved to 50.7±11, 53.3±13.1, 54.9±13.9 and 57.1±10.1 ml/min at 1, 3, 6 and 12 months post conversion respectively (p=0.028 at 3 months). The eGFR showed futher improvement. After a total 471 patient treatment months, there were no episodes of rejection CMV or BK virus infection. Of 22 patients, certican was withdrawn in 2 patients at 12 months & 24 months due to appearance of proteinuria. Conclusion: Late conversion from mycophenolate to everolimus with CNI minimization resulted in stabilization of renal function with no evidnece of Rejection or infections.