Renal Function and NODM in De Novo Renal 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.

Figure 1

Mean tacrolimus trough levels over time. Tac = tacrolimus; Group A = low-dose tacrolimus (n = 151); Group B = standard-dose tacrolimus (n = 141); “reclassified” defined as >50% of Tac levels (mandatory requirement for month 6 assessment) being within a protocol-specified Tac target range. Bars represent one standard deviation. Shaded areas represent protocol specified target ranges for tacrolimus.

Figure 2

Incidence of new onset diabetes mellitus at month 3, 6, and overall (safety population Group A, n = 114; Group B, n = 109). NODM = patients treated for hyperglycemia for a period of 14 consecutive days, or had 2 h OGTT posttest value ≥200 mg/dL, or had at least two fasting glucose values ≥126 mg/dL, or had one single random value (fasting or nonfasting) ≥mg/dL. Safety population, patients with diabetes mellitus active at start of study, was excluded.