Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters

Abstract

Background. Calcineurin inhibitors (CNIs) and steroids are strongly associated with new-onset diabetes after transplantation, worsening of pre-existing diabetes, and cardiovascular events. We assessed the benefit of conversion from CNI-based to belatacept-based immunosuppression in diabetic kidney-transplant (KT) recipients on glucose control and cardiovascular risk factors. Methods. In this retrospective, noncontrolled single-study conducted between May 2016 and October 26, 2018, we recruited KT recipients converted from CNIs to belatacept at least 6 months after KT. The primary endpoint was the evolution of hemoglobin A1c (HbA1c) between baseline and after 6 months of treatment. Secondary endpoints included modifications to antidiabetic drugs, other cardiovascular risk factors, and renal function. Results. One hundred and three KT recipients were included. Of these, 26 (25%) had type 2 diabetes. The patients were either receiving oral antidiabetic drugs (n = 21; 75%) or insulin therapy (n = 14; 54%). Overall HbA1c decreased significantly from 6.2 ± 1 to 5.8 ± 1%, P < 0.001. In diabetic patients, HbA1c decreased from 7.2 ± 1 to 6.5 ± 1%, P = 0.001. HbA1c significantly decreased in the subgroup of patients with new-onset diabetes after transplantation and whether diabetes was controlled at inclusion or not (ie, HA1c ≤7% or >7%). Moreover, no diabetic patient increased the number of oral antidiabetic drugs and the dose of basal insulin was not statistically different from baseline to 6 months (16 international unit at baseline and 16 international unit at 6 mo, P = 1). One patient had to start treatment by insulin pump. During follow-up, the renal function, body mass index, and hemoglobin level of all 103 patients remained stable, 2 patients presented acute cellular rejection, and no patient suffered from graft loss. Conclusions. A late switch from CNI to belatacept was a valuable therapeutic option for diabetic kidney recipients and substantially improved glycemic parameters.

Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

“…The tacrolimus‐treated kidney transplant recipients had lower insulin release in the presence of higher insulin sensitivity, when compared to belatacept‐treated kidney transplant recipients. The study also confirmed a lower PTDM rate with belatacept, compared to tacrolimus [62], which has recently been observed in another retrospective study [63]. The tacrolimus‐belatacept comparison represents new information, as the available literature had previously only suggested superiority of belatacept, in terms of a reduced PTDM incidence [64,65], when this immunosuppressive agent was compared to cyclosporine.…”

Glucose Metabolism After Kidney Transplantation: Insulin Release and Sensitivity With Tacrolimus- Versus Belatacept-Based Immunosuppression

“…To our knowledge, only one publication has recently provided data on differences in glucose metabolism between tacrolimus and belatacept-treated patients. 9 This retrospective study on 112 KTRs transplanted for ≥6 months, who were thereafter converted to belatacept for nephroprotection, identified an improvement in HbA1c levels in diabetic and nondiabetic KTRs. 9 Changes in insulin secretion and/or sensitivity were unfortunately not reported.…”

“…9 This retrospective study on 112 KTRs transplanted for ≥6 months, who were thereafter converted to belatacept for nephroprotection, identified an improvement in HbA1c levels in diabetic and nondiabetic KTRs. 9 Changes in insulin secretion and/or sensitivity were unfortunately not reported. 9 These findings are limited by the possibility of confounding due to differences between the groups at baseline and during follow-up, especially worse kidney function and lower magnesium levels among tac-KTRs.…”

“…9 Changes in insulin secretion and/or sensitivity were unfortunately not reported. 9 These findings are limited by the possibility of confounding due to differences between the groups at baseline and during follow-up, especially worse kidney function and lower magnesium levels among tac-KTRs. However, even if either or both of these factors accounted for the differences observed in our study, each is a commonly recognized complication of tacrolimus, but not belatacept.…”

Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

“…Indeed, in the BENEFIT study, after a 7-year follow-up, patient-and graft-survival rates were significantly higher in patients treated with belatacept compared to those treated with cyclosporine [8]. Recently, we have shown that a late switch from CNIs to belatacept was a valuable therapeutic option for diabetic kidney-transplant recipients and substantially improved glycemic parameters [12]. Lastly, belatacept has also shown potential benefits by lowering the appearance of de novo donor-specific alloantibodies (DSAs) after KT and by decreasing pre-existing DSAs [13,14].…”