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While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean +/- SD age was 38.5 +/- 15.6 years, including pediatric and geriatric age groups. Mean +/- SD body mass index (BMI) was 28.99 +/- 8.0 and 40% had a BMI30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean +/- SD time to start of SRL was 11.9 +/- 22.8 months posttransplantation. Proteinuria2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P = .001, P = .0003, and P = .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P.0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.

Objective. The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. Methods. Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. Results. There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was 90% for peak cyclosporine blood levels (P

Background. We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction. Patients and Methods. In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)―mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded. Results. Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome. Conclusion. Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.

Introduction Cyclosporine microemulsion has been the mainstay immunosuppressive agent in renal transplantation for years. Since single daily dosing of cyclosporine is rarely used, the objective of this investigation was to evaluate the efficacy of a single daily dose versus twice daily dosing of cyclosporine in renal transplant recipients. Methods Retrospective evaluation of single-dose cyclosporine use was conducted for 15 renal transplant recipients for 12 months (study group). Equal numbers of matched renal transplant recipients were selected for age, sex, human leukocyte antigen mismatch, donor type, and immunosuppressive regimen (control group). Cyclosporine trough level and peak cyclosporine blood levels, 12-hour cyclosporine profile, and the area under the concentration-time curve were measured. Results There was a significant difference in cyclosporine peak blood level and calculated area under the curve after shifting to single-dose cyclosporine (P = .001). In the study group, the mean area under the curve was significantly below the average therapeutic range before (3154 ng/mL/ho) versus 5532 ng/mL/h after shifting to the single-dose regimen (which was therapeutic). This value was 5749 ng/mL/h in the control group. Total daily cyclosporine dose was lower in the study group when compared with the control group at 6 and 12 months (P = .01). There were significantly fewer adverse effects in patients in the study group than in patients in the control group. Conclusion We conclude that although cyclosporine dose should be individualized in renal transplant recipients, a single dose of cyclosporine has the added advantage of decreasing dosages and cyclosporine-related adverse effects while maintaining optimal graft function.

Aseptically processed and packaged dairy fluids were investigated for stability during long-term storage. Model solutions of whey and sodium caseinates, and combinations of them with milk fat were used. Sedimentation in whey protein solutions was extensive. No significant sedimentation was observed in casein solutions even after 500 days of storage. Addition of milk fat retarded sedimentation in whey protein solutions initially. Very little fat separation was observed in whey-fat solutions. Larger amounts of fat separation were observed in casein-fat or casein-whey-fat solutions. Casein-whey-fat sediments were in the form of a gel. Sporadic gelation was observed in casein solutions. Sedimentation rates from cheese whey alone are similar to gelation rates for milk for similar thermal treatments. Reactivated enzymes may be responsible for both phenomena.