Rapid Discontinuation of Prednisone in Kidney Transplant Recipients

Abstract

Background Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. Methods From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult 1st and 2nd kidney transplants—1021 with a living donor (LD), 532 with a deceased donor (DD)—under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored graft survival (DCGS), and acute rejection–free survival (ARFS) rates for RDP compared to historical controls on maintenance prednisone. Results For LD recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (p=0.02) and DCGS (p=0.01). For DD recipients, RDP was associated with significantly better PS (p<0.01), GS (p<0.01) and DCGS (p<0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, CMV, cataracts, NODAT and cardiac complications. Importantly, for recipients with graft survival >5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. Conclusion In summary, at 15-years post kidney transplant, RDP did not lead to decreased in patient or graft survival, or an increase in graft dysfunction but as associated with reduced complication rates.

Belatacept-based immunosuppression with simultaneous calcineurin inhibitor avoidance and early corticosteroid withdrawal: A prospective, randomized multicenter trial

“…The BEST trial has implications for a number of transplant‐related complications. ESW experiences have shown reduced cardiovascular risk/cardiovascular events and improved cardiovascular survival; therefore, it seems reasonable that additional reduction in cardiovascular risk/events will be provided by simultaneous CNIA/ESW . Moreover, CNIA/ESW should further minimize drug‐related toxicity, specifically neurotoxicity, gastrointestinal toxicity, and NODAT, thereby enhancing quality of life.…”

“…Calcineurin inhibitors (CNIs) have been the cornerstone of immunosuppressive therapy in transplant for almost 4 decades. CNI‐based therapy, however, is complicated by significant adverse events, including hypertension, hyperlipidemia, and new‐onset diabetes after transplant (NODAT), leading to increased cardiovascular events and cardiovascular morbidity and mortality . CNIs are also associated with significant toxicities, including nephrotoxicity, neurotoxicity, and gastrointestinal (GI) toxicity.…”

“…CNIbased therapy, however, is complicated by significant adverse events, including hypertension, hyperlipidemia, and new-onset diabetes after transplant (NODAT), leading to increased cardiovascular events 1 and cardiovascular morbidity and mortality. 2 CNIs are also associated with significant toxicities, including nephrotoxicity, neurotoxicity, and gastrointestinal (GI) toxicity. Another shortcoming of CNI-based therapy is the development of donor-specific anti-HLA antibodies (DSAs) in 10%-15% of patients at 1 year after transplant, 3 which is associated with reduced renal allograft survival.…”

Rapid discontinuation of prednisone in kidney transplant recipients from at‐risk subgroups: an OPTN/SRTR analysis

“…Two prospective randomized studies comparing RDP with maintenance prednisone found no significant difference in patient survival, graft survival, or renal function at 5 years post‐transplant. In a single‐center analysis of 1st and 2nd transplant recipients, we found no difference in 15‐year patient or graft survival between those on RDP and those on maintenance prednisone . In a subanalysis of that study, we compared recipients with at least 5‐year graft survival on RDP ( n = 859) versus maintenance prednisone ( n = 317) and found no difference between groups in patient or graft survival between 5 and 15 years post‐transplant.…”

Predictors of Avascular Necrosis after Kidney Transplantation

“…Patients exposed to higher corticosteroid doses or those who underwent corticosteroid treatment for longer durations were considered to be at a higher risk for AVN (2,22).…”