INTESTINAL PERMEABILITY IN PATIENTS AFTER KIDNEY TRANSPLANTATION TREATED WITH TWO DIFFERENT FORMULATIONS OF EXTENDED-RELEASE TACROLIMUS

Abstract BACKGROUND AND AIMS A prompt achieving of adequate tacrolimus blood exposure is crucial in early period after kidney transplantation. A gut epithelial barrier integrity may play a role in tacrolimus absorption. The aim of this study was to investigate the intestinal fatty acid binding protein (I-FABP) concentrations as a marker of intestinal permeability in recent kidney transplant recipients (KTRs) treated with two different tacrolimus extended-release formulations. METHOD 48 pairs of consecutive KTRs were analyzed. Within each pair, an early conversion was performed from twice-daily (Prograf) to a once-daily tacrolimus formulation: Advagraf or Envarsus. On the day of discharge from the hospital, I-FABP plasma levels were measured and the tacrolimus concentration-to-dose (C/D) ratio was calculated. Tacrolimus exposure was assessed with an area under the curve (AUC) based on blood trough level and 3-h post-dose measurement. RESULTS There were no differences in recipient age, dialysis vintage, BMI and residual diuresis between the Advagraf and Envarsus groups. The median I-FABP plasma levels [Advagraf: 1450 (750–2100) versus Envarsus 1200 (600–1790) pg/mL; P = .18] and mean tacrolimus AUC [154 (143–164) versus 145 (132–158) ng.h/mL, respectively; P = .30] were similar. As expected, C/D ratio was significantly greater in the Envarsus group [2.06 (1.32–3.09) versus 1.16 (0.72–1.52) in the Advagraf group; P < .001]. Interestingly, log I-FABP correlated inversely with tacrolimus AUC only in the Envarsus group (r = –0.431; P < .01) but not in the Advagraf group (r = 0.05; P = .72). CONCLUSION Our findings suggest that destabilization of the enterocyte membrane integrity may influence the intestinal tacrolimus absorption, which may cause lower tacrolimus exposure in KTRs treated with Envarsus. However, explanation of this phenomenon needs further investigation.