Role of steroid maintenance in sensitized kidney transplant recipients

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 TransplantNetwork/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 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.

Steroid withdrawal or avoidance is safe in high‐risk kidney transplants: A systematic review and meta‐analysis

“…Five studies reported graft loss events for both the experimental and control groups, and the other three studies reported graft loss HRs for SWA . The pooled analysis of graft loss events found no difference between the SWA and CSM groups (RR = 0.54, 95% CI 0.29‐1.00, P = 0.05).…”

“…A flow chart of the screening process is presented in Figure . Six studies focused on African Americans, one on repeat kidney transplantation, and one on sensitized patients . The investigators divided the sensitized population into three groups based on their PRA levels (0%‐30%, 30%‐60%, and >60%) but included data from only the latter two groups for further evaluation …”

“…One study applied a steroid avoidance protocol in the experimental arm, four studies reported very early steroid withdrawal within 1 week, two studies withdrew steroids at hospital discharge, and one study reported steroid withdrawal 3‐5 months after kidney transplantation . Given that the average length of hospital stay in the United States is from 4 to 5 days, we considered steroid withdrawal at hospital discharge as very early steroid withdrawal.…”

“…The follow‐up period varied from 12 to 120 months. Five studies initiated tacrolimus with mycophenolate mofetil as the maintenance regimen, and two used tacrolimus/sirolimus and mycophenolate mofetil …”

“…Three studies reported mortality events for both study groups, whereas the other three studies reported HRs of mortality for SWA . Pooled analysis of events found that SWA was not associated with an increased risk of death (RR = 0.40, 95% CI 0.11‐1.52, P = 0.18), and pooled analysis of HRs found a reduced risk of death for SWA (RR = 0.91, 95% CI 0.84‐0.98, P = 0.01).…”