Role of steroid maintenance in sensitized kidney transplant recipients

AIM: To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance(CSM) emerge. METHODS: Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal(ESW) among patients who underwent deceased-donor kidney(DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody(peak-PRA) titers(0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor(CNI) and mycophenolate mofetil(MMF).RESULTS: The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure(HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patientdeath(HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk(HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM(n = 25218) vs ESW(n = 7399). Over-all(HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored(HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk(HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM(n = 3495) vs ESW(n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure(HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patientdeath(HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower(HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM(n = 4966)vs ESW(n = 923).CONCLUSION: In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

Impact of steroid maintenance on the outcomes in firsttime deceased donor kidney transplant recipients: Analysis by induction type

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received.METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbitantithymocyte globulin(r-ATG), alemtuzumab or an interleukin-2 receptor blocker(IL-2B) and discharged on a calcineurin inhibitor(CNI)/mycophenolate mofetil(MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database.For each induction type, adjusted overall and deathcensored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups.RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG(steroid = 13001, nosteroid = 4862), 3028 alemtuzumab(steroid = 852, no-steroid = 2176) and 16326 IL-2B(steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior(HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival(HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs nosteroid groups were similar in alemtuzumab(HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B(HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs nosteroid groups in r-ATG induced(HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab(HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B(HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune(HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune(HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low(HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high(HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune(HR =1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune(HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids. CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.