A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients

Edward H Cole,Joseph S Kim,David N Landsberg,Jeffrey S Zaltzman,Daniel C Cattran,Kathryn J Tinckam,Gv Ramesh Prasad,Jeffrey R Schiff,Carl J Cardella,John S Gill

doi:10.1186/2047-1440-2-1

Abstract

BackgroundNew onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation.MethodsIn this multi-center, open label, single-arm pilot study, 49 adult (≥18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin® (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy.ResultsSix months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR. Four patients had impaired fasting glucose tolerance based on 75-g oral glucose tolerance testing (OGTT). There was one patient death. There were no episodes of cytomegalovirus (CMV) infection or BK virus nephritis. In contrast, in a historical cohort of n = 27 patients treated with Thymoglobulin induction, and conventional doses of cyclosporine and corticosteroids, the incidence of NODM and AR was 18% and 15%.ConclusionsThe pilot study results suggest that Thymoglobulin induction combined with early steroid reduction, reduced cyclosporine exposure and MPA, may reduce the incidence of both NODM and AR in low immunological risk patients. A future controlled study enriched for patients at high risk for NODM is under consideration.Trial registrationClinicalTrials.gov: http://NCT00706680

Highlights

New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation
There is evidence that glucose tolerance is not significantly different among patients treated with low dose prednisone (5 mg/day) and those treated with complete steroid withdrawal [8]
Thirty percent had Body mass index (BMI) >30 and 82% of patients were unsensitized whereas 18% had a panel reactive antibody (PRA) of 1 to 20%

Summary

Introduction

New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation. New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure by 5 years [3]. Strategies to reduce NODM while maintaining low rates of AR would have the potential to improve long-term outcomes. Recent studies have shown that early steroid withdrawal had limited impact on NODM, but was associated with a higher incidence of AR [4,5]. It is possible that early steroid withdrawal was not as successful in reducing this metabolic complication as hoped, in part, because of relatively high calcineurin inhibitor doses in one study and the use of tacrolimus in the other [7]. The main barriers to wider acceptance of steroid elimination are a higher incidence of AR, the absence of clinically relevant improvements in metabolic parameters and hypertension, and concerns about long-term safety

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