Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 24, 2015; 5(3): 102-109
Published online Sep 24, 2015. doi: 10.5500/wjt.v5.i3.102
Role of steroid maintenance in sensitized kidney transplant recipients
Kalathil K Sureshkumar, Richard J Marcus, Bhavna Chopra
Kalathil K Sureshkumar, Richard J Marcus, Bhavna Chopra, Division of Nephrology and Hypertension, Department of Medicine, 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; Marcus RJ participated in research design, performance of the research and data analysis; Chopra B participated in data analysis and writing of the manuscript.
Institutional review board statement: IRB approval of the study protocol attached (Allegheny-Singer Research Institute).
Informed consent statement: This study was exempted from the need for informed consent (see attached IRB certification of exemption).
Conflict-of-interest statement: No conflict-of-interest to declare.
Data sharing statement: This study was performed using the OPTN/UNOS data base which is publically available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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: February 24, 2015
Peer-review started: February 26, 2015
First decision: June 3, 2015
Revised: June 11, 2015
Accepted: August 13, 2015
Article in press: August 14, 2015
Published online: September 24, 2015
Abstract

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 patient-death (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 patient-death (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.

Keywords: Sensitization, Kidney transplantation, Graft survival, Steroid withdrawal, Older kidney transplant recipients

Core tip: This study critically evaluated the role of steroid maintenance in kidney transplant recipients (KTR) based on the level of sensitization by utilizing the Organ Procurement and Transplant Network/United Network of Organ Sharing database. In the multivariate model, we found an association between increased risk for death with functioning graft and steroid maintenance in KTRs who had peak-panel reactive antibody < 30% and received perioperative induction therapy followed by calcineurin inhibitor/mycophenolate mofetil maintenance. On the other hand, steroid maintenance was associated with improved death-censored graft survival without adversely impacting patient survival in KTRs with a peak PRA > 60%. No benefits of steroid maintenance were observed in older KTRs regardless of level of sensitization. These finding have clinical relevance and should be further evaluated in randomized clinical trials.