Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73852/1/j.1600-6143.2003.30111.x.pd

Immunosuppression: Evolution in Practice and Trends, 1994–2004

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73911/1/j.1600-6143.2006.01270.x.pd

Fixed- or Controlled-Dose Mycophenolate Mofetil with Standard- or Reduced-Dose Calcineurin Inhibitors: The Opticept Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74911/1/j.1600-6143.2009.02668.x.pd

Belatacept and long-term outcomes in kidney transplantation

Background: in previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. Methods: we randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). Results: a total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. Conclusions: seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750)

Calcineurin inhibitor-free immunosuppression in kidney transplantation

The introduction of calcineurin inhibitors (CNI) revolutionized kidney transplantation (KTx). Exceptionally low acute rejection rates and excellent graft survival could be achieved with CNI-based (cyclosporine and tacrolimus) immunosuppressive protocols. However, despite short-term success, long-term graft attrition continues to be a significant problem, thus leaving clinicians looking for possible interventions. CNI nephrotoxicity is but one of numerous factors that may be contributing to long-term damage in transplant kidneys. Therefore, newer immunosuppressive agents such as mycophenolate mofetil and sirolimus (Rapa) have raised the possibility of withdrawing or avoiding CNIs altogether. Protocols exploring these options have gained greater attention over the last few years. Herein, we review studies addressing either CNI withdrawal or CNI avoidance strategies as well as discuss the risks versus benefits of these protocols. Given the accumulated experience to date, in our opinion, the use of CNIs as a part of immunosuppressive regimens remains the proven standard of care for renal transplant patients. The long-term safety and efficacy of CNI withdrawal and avoidance strategies need to be further validated in controlled clinical trials

Half of Kidney Transplant Candidates Who Are Older than 60 Years Now Placed on the Waiting List Will Die before Receiving a Deceased-Donor Transplant

Background and objectives: Waiting times to deceased-donor transplantation (DDTx) have significantly increased in the past decade. This trend particularly affects older candidates given a high mortality rate on dialysis

Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study

The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation. Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm. The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm. This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded