Renal Function and NODM inDe NovoRenal Transplant Recipients Treated with Standard and Reduced Levels of Tacrolimus in Combination with EC-MPS

Abstract

Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study, de novo RTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation. Secondary objectives were to compare the incidences of biopsy-proven acute rejection (BPAR), graft loss and death, and new-onset diabetes mellitus (NODM). 292 patients (LD n = 151, SD n = 141) were included. Mean Tac levels were at the low end of the target range in standard-exposure patients (SD, n = 141) and exceeded target range in low-exposure patients (LD = 151) throughout the study. There was no significant difference in mean glomerular filtration rate (GFR) between treatments (ITT-population: 63.6 versus 61.0 mL/min). Incidence of BPAR was similar (10.6% versus 9.9%). NODM was significantly less frequent in LD Tac (17% versus 31%; P = 0.02); other adverse effects (AEs) were comparable. EC-MPS+Tac (LD/SD) was efficacious and well tolerated with well-preserved renal function. No renal function benefits were demonstrated, possibly related to poor adherence to reduced Tac exposure.

A Prospective Study of Renal Transplant Recipients: A Fall in Insulin Secretion Underpins Dysglycemia After Renal Transplantation

“…1-5 Furthermore, by defining glycemic state with reference to 12 month data we excluded transient dysglycemia as recommended by the International Consensus on Posttransplant Diabetes. 6 Consistent with others, 10,14 we noted changes in definitional states (IGT vs PTDM) over the first year; however, found stability in the more granular definition of persistent dysglycemia.…”

“…Calcineurin inhibitors (CNI) and glucocorticoids form the backbone of most immunosuppressive regimens and are well described risk factors for posttransplant dysglycemia. 14,15 The diabetogenic potential of glucocorticoids is well established and encompasses both increased insulin resistance and reduced insulin secretion. In addition, CNI reduce insulin secretion through a direct toxic effect on the β cell.…”

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta‐Analysis

“…The most widely reported strategy identified by our literature search was CNI minimization, implemented by reducing target trough levels. Thirty‐six RCTs (Table S4) examining dose minimization were identified: 22 studies used CsA, 7 used tacrolimus and 7 incorporated both. Mycophenolic acid formulations (mycophenolate mofetil [MMF] or enteric‐coated mycophenolate sodium [MPS]) were used as adjuvant agents in 19 studies, and 14 used mammalian target of rapamycin (mTOR) inhibitors in addition to CNI.…”

Dynamics of Glucose Metabolism After Kidney Transplantation

“…Calcineurin inhibitors lead to impaired β-cell growth and function [42], in which tacrolimus is more diabetogenic than ciclosporin [43]. Reversal of manifest PTDM after conversion from tacrolimus to ciclosporin has been shown [44], however, newer studies point towards a dosing effect of the diabetogenic potential [45]. Current guidelines recommend not to choose or alter immunosuppression according to the risk of PTDM [12] since the risk of allograft injury outweighs the potential benefit of an improvement in glucose metabolism with regard to patient prognosis.…”