Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 24, 2014; 4(3): 188-195
Published online Sep 24, 2014. doi: 10.5500/wjt.v4.i3.188
Impact of steroid maintenance on the outcomes in first-time deceased donor kidney transplant recipients: Analysis by induction type
Kalathil K Sureshkumar, Sabiha M Hussain, Ngoc L Thai, Tina Y Ko, Khaled Nashar, Richard J Marcus
Kalathil K Sureshkumar, Sabiha M Hussain, Tina Y Ko, Khaled Nashar, Richard J Marcus, Divisions of Nephrology and Hypertension, Department of Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Ngoc L Thai, Abdominal Transplantation, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Author contributions: Sureshkumar KK participated in research design, performance of the research, data analysis and writing of the manuscript; Hussain SM participated in research design and data analysis; Thai NL participated in research design and data analysis; Ko TY and Nashar K participated in data analysis; Marcus RJ participated in research design, performance of the research and data analysis.
Supported by Health Resources and Services Administration Contract 231-00-0115
Correspondence to: Kalathil K Sureshkumar, MD, FRCP (Glasgow), FASN, Division of Nephrology and Hypertension, Department of Medicine, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212, United States. ksureshk@wpahs.org
Telephone: +1-412-3593319 Fax: +1-412-3594136
Received: March 24, 2014
Revised: June 5, 2014
Accepted: July 25, 2014
Published online: September 24, 2014
Processing time: 213 Days and 17.6 Hours
Abstract

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 rabbit-antithymocyte 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 death-censored 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, no-steroid = 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 no-steroid 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 no-steroid 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.

Keywords: Induction agent, Steroid maintenance, Graft failure risk, Patient death risk, High immune risk

Core tip: This study critically looked at outcomes in a large recent cohort of first time deceased donor kidney transplant recipients from the Organ Procurement and Transplant Network/United Network of Organ Sharing database to assess the impact of triple maintenance immunosuppression after receiving various induction therapies. In multivariate analysis, we found an increased risk for death with functioning graft when steroid maintenance was added to calcineurin inhibitor/mycophenolate mofetil based regimen in patients who received powerful induction with rabbit-antithymocyte globulin (r-ATG), an effect that persisted even when patients were split into high and low immune risk groups. Based on these finding we feel that, one has to be cautious while maintaining intense immunosuppression by adding steroid to a calcineurin inhibitor/mycophenolate mofetil regimen in kidney transplant recipients who were selected for r-ATG induction.