Identifying cyclosporine blood levels associated with the prevention of renal transplant rejection: a single-center, randomized prospective study.

Multiple-drug therapy may allow reduced individual drug doses with fewer side effects. Blood levels of cyclosporine (CsA) necessary to avoid rejection may vary with different drug combinations. Fifty-eight kidney transplant patients were randomized into two groups: 25 subjects were assigned to the 4-hour area under the curve (AUC(0-4)) Cohort-the "high arm" (4500 to 5500 ng . h/mL)--1 and 33 to the AUC(0-4) "low arm" (2400 to 3400 ng . h/mL). After CsA introduction, AUC(0-4) was drawn on days 4, 7, 14, 21, 28, 42, 56, 70, 84, 90. We compared the proportion of rejection versus rejection-free patients, according to the CsA exposure. Logistic regression analysis showed that an AUC(0-4) of > or =4000 ng . h/mL or a 2-hour cyclosporine level (C(2)) of > or =1450 ng/mL predicted a rejection-free course among patients not receiving induction therapy. When either basiliximab or thymoglobulin was administered, a C(2) and AUC(0-4) of 1043 +/- 151 ng/mL or 3146 +/- 262 ng . h/mL, respectively, were associated with a rejection-free course. Our findings confirm the need for different CsA levels to prevent rejection according to induction therapy. Induction with either basiliximab or thymoglobulin allows reduced CsA levels during the first 3 months after renal transplantation.

Introduction of mycophenolate mofetil and cyclosporin reduction in children with chronic transplant nephropathy.

Chronic transplant nephropathy (CTN) is the most important cause of kidney graft dysfunction. Studies in adult populations have reported a beneficial effect of non-nephrotoxic mycophenolate mofetil (MMF) on graft function in this setting. However, few studies were reported in children in this setting. We therefore reviewed the charts/medical records of renal transplanted patients < 18 yr of age at a single center who had switched from azathioprine to MMF as a result of progressive loss in graft function, for which vascular, infectious, and urological causes were excluded. Serum creatinine (SCr) and calculated creatinine clearance were compared prior to and after MMF introduction. Thirteen patients (nine male/four female), followed-up for 59.3 +/- 35.4 months after transplantation, were analyzed. Age at MMF introduction was 14.2 +/- 3.6 yr. In 11 patients a previous biopsy had shown features of CTN and four patients also presented signs of chronic cyclosporin A (CsA) nephrotoxicity. MMF was started at a dose of 1211 +/- 351 mg/day, and the CsA dose was decreased from 6.69 +/- 3.15 mg/kg/day 6 months before MMF to 4.8 +/- 2.3 mg/kg/day at the time of MMF introduction. CsA was withdrawn in four patients. The median (25-75%) SCr value increased from 1.60 mg/dL (range 1.3 to 1.87 mg/dL) 6 months before MMF to 2.2 mg/dL (range 1.87-2.32 mg/dL) when MMF was introduced. Six months after introduction of MMF, the SCr level had decreased to 1.5 mg/dL (range 1.2-1.8 mg/dL) and remained stable until the last follow-up (17.5 +/- 9.2 months after MMF was started). A similar pattern occured with calculated SCr clearance. There were no acute rejections after changes in immunosuppression. The safety of MMF was also analyzed and in only one patient was the drug stopped as a result of intractable diarrhea. These findings suggest that MMF is sufficiently powerful to allow a decrease/withdrawal of CsA without the burden of acute rejection in a pediatric population with CTN.

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% for both assays. The cost for each CyA measurement was 50% 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.