The dynamics of glucose metabolism under calcineurin inhibitors in the first year after renal transplantation in nonobese patients.

BACKGROUND: The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant. METHODS: Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids. RESULTS: The incidence of impaired glucose tolerance or diabetes mellitus reached a peak at 60 days and decreased at 1 year. It could not be adequately diagnosed using fasting plasma glucose in a decreased abnormal (>99 ng/mL) range. In both groups, insulin secretion, evaluated by the Homeostasis Model Assesment (HoMA-beta), decreased (P<0.005) from the condition of normal GTT (101+/-56%) to impaired glucose tolerance (72+/-35%) and diabetes mellitus (54+/-25%). In the cyclosporine group, insulin secretion was normal and stable throughout the study period, but in the tacrolimus group, insulin secretion recovered over time and was inversely correlated with tacrolimus exposure. Insulin resistance (HoMA-IR) did not change. CONCLUSIONS: This study shows the need to perform an oral GTT at 60 days and at the end of the first year of renal transplantation to adequately diagnose impaired glucose metabolism.

Sampling strategy to calculate the cyclosporin-A area under the time-concentration curve.

The complete area under the time-concentration curve (AUC) is considered to be the gold standard for cyclosporin-A (CyA) monitoring. However, complete AUC is time- and cost-consuming. For this reason, we reviewed 259 4-h AUC (AUC0-4) performed in 74 renal transplanted patients in order to construct an equation to calculate AUC0-4. All samples were drawn from one adult population 13 days following transplantation, in order to allow the cyclosporin metabolism to stabilize. Regression analysis was done either with each or with a combination of two variables. Cyclosporin-A blood concentration at the second hour after the oral dose (C2) was the best predictor of AUC0-4, where AUC0-4 = 451 +(2.73 x C2), R2 = 0.87, p<0.001. The combination of C1 and C2 only, offered a better mathematical improvement to the C2 equation. This equation was further validated in 33 other CyA pharmacokinetic profiles performed in eight patients who had not participated in the equation development. In this new population, the C2 equation excellently predicted the trapezoidal AUC0-4 (R2 = 0.81). Our data shows that C2 can be safely used to estimate AUC0-4. The C2 equation simplifies CyA monitoring because of its high-predictive value and clinical feasibility.

Comparison of the fluorescent polarization (TDx) and the enzymatic competitive (EMIT 2000) immune assays for the measurement of cyclosporin A blood concentration

Evaluation of Cyclosporin A (CyA) blood concentration is imperative in solid organ transplantation in order to achieve maximal immunosuppression with the least side effects. We compared the results of whole blood concentrations of CyA in 50 blood samples simultaneously evaluated by the fluorescent polarization immune assay (TDx) and the enzymatic competitive immune assay (EMIT 2000). There was a strong correlation between both kits for any range of CyA blood concentration (R=0.99, p<0.001). The within-run and between-days coefficient of variation were less than 4 percent for both assays. The cost for each CyA measurement was 50 percent lower for the EMIT assay when compared to the TDx assay. We concluded that the EMIT is as accurate as the TDx in measuring CyA blood concentration and has the advantage of a lower cost, as well as the possibility of widespread access to the EMIT methodology in contrast to the TDx equipment, allowing the laboratory to perform several routines within a working day