Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring.

BACKGROUND: With effective agents available to prevent posttransplantation acute organ rejection, medication adherence becomes a key factor for successful treatment outcomes after renal transplantation. A once-daily, modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence. METHODS: Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a randomized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake. After enrolment, all patients continued the twice-daily regimen for 3 months and then were randomized 2:1 between the two formulations and followed for 6 months. Adherence was decomposed into patients' persistence and implementation of each regimen. RESULTS: Two hundred nineteen patients (45% male; 3±2 years after transplantation) were analyzed (145 once daily and 74 twice daily). At 6 months after randomization, 81.5% of the once-daily group and 71.9% of the twice-daily group remained persistent with the treatment (P=0.0824). Among patients who remained engaged with the regimen, 88.2% of the once-daily group and 78.8% of the twice-daily group (P=0.0009) took the prescribed number of daily doses. When the patients took the twice-daily regimen, the average percentage of missed doses was 11.7% in the morning and 14.2% in the evening (P=0.0035). CONCLUSIONS: Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen. There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification. Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management.

Ineligibility for renal transplantation: prevalence, causes and survival in a consecutive cohort of 445 patients.

Little is known about the proportion of renal transplant candidates who are considered ineligible by the transplant center, the reasons of their ineligibility and their survival during dialysis. In this retrospective, single-center study of 445 adult patients referred between 2001 and 2006, 36 (8%) were deemed ineligible for medical contraindications. The leading reason was cardiovascular (CV) (75%), specifically aorto-iliac, and/or limb vessels atheromatosis or calcifications; ischemic heart disease; or a combination thereof. Nine patients had other contraindications that were absolute for three of them; six patients displayed a combination of relative contraindications. When compared to eligible patients (N = 409), those ineligible were significantly older (60 yr vs. 48), more often diabetics (50% vs. 15%), obese (39% vs. 17%) suffering from coronary artery disease (53% vs. 11%) and peripheral arterial disease (86% vs. 11%). Their primary nephropathy was more often diabetic and/or hypertensive/nephroangiosclerosis (61% vs. 23%), and their median dialysis vintage prior to evaluation was longer (29 months vs. 10, p < 0.0001). The actuarial survival of ineligible patients was significantly lower than that of eligible patients (at five yr: 53% vs. 88%). Adequate control of CV risk factors before dialysis and early referral for transplantation might help to improve eligibility of renal transplant candidates.