Long-range post-kidney transplant corticosteroids may not be necessary for most patients, researchers reported.
In new long-term data (median 15.8 years) on 191 patients who withdrew from corticosteroids 7 days after undergoing a kidney transplant, versus 195 patients who continued steroids, there was no significant difference in the risk of allograft failure from any cause including death (adjusted hazard ratio 0.83, 95% CI 0.62-1.10, P=0.19), reported John S. Gill, MD, of St Paul’s Hospital in Vancouver, and colleagues.
There was also no significant difference in the risk of allograft failure (not including patient death), defined as a need for long-term dialysis or repeat transplant during a median follow-up period of 15.8 years (aHR 0.78, 95% CI 0.52-1.19, P=0.25), they reported in JAMA Surgery.
These data build on previously reported 5-year outcomes from the same group. In that study, they found a slightly higher rate of biopsy-confirmed acute rejection after steroid withdrawal versus continuation of steroids (34/191 (17.8%), 21/195 (10.8%), P=0.058). However, 5-year renal allograft survival and function rates were similar. Those who didn’t continue chronic low-dose corticosteroid therapy saw better outcomes for cardiovascular (CV) risk factors, including lower triglycerides, less weight gain, lower blood glucose, and less need for insulin, according to the authors.
But they stressed that a study limitation was lack of data on long-term differences in nonfatal outcomes, such as CV disease, diabetes, infections, and metabolic bone disease between the two groups of patients.
Gill and colleagues also pointed out that only about 30% of all transplant recipients withdraw from steroid therapy.
“Factors contributing to continued use of corticosteroids include concerns about long-term safety and uncertainty about the modest metabolic benefits of corticosteroid withdrawal,” they explained. “In contrast, proponents of corticosteroid withdrawal hypothesized that longer follow-up might be required for the metabolic benefits to affect outcomes.”
The trial included 385 kidney transplant patients (ages 18 to 70) with low- to moderate-immune risk — defined as peak panel reactive antibody less than 50% and pretransplant panel reactive antibody less than 25% — at 28 U.S. kidney transplant centers. Surgeries took place between 1999 and 2021, and all patients received either a living or deceased donor kidney transplant without delayed graft function. None had short-term rejection in the first week after transplant.
Half of the patients were randomized to receive the immunosuppressant drugs tacrolimus (Envarsus, Protopic, Astagraf) and mycophenolate mofetil with prednisone and withdraw 7 days after transplant. The other half continued prednisone (5 mg/d after 6 months post-transplant).
Although these patients were relatively low risk to begin with, Arthur Matas, MD, of University of Minnesota in Minneapolis, pointed out that other data have suggested that the practice of early steroid cessation (ESC) — withdrawing within 14 days — has also shown some success with higher-risk groups such as Black patients, children, and even those with re-transplants or recurring disease.
“The authors question why ESC is not used more widely. I agree,” Matas wrote in an invited commentary. He added that the success of early steroid cessation has led many transplant centers to cut down on prednisone use to just 5 mg per day.
“However, even this low dose is associated with complications (e.g., osteoporosis, fractures),” he noted. “Going forward, in contrast with justifying ESC, transplant centers using steroids should justify why they are using steroids for their recipients or recipient subpopulations, given that there is no evidence of improved outcomes and steroids have adverse effects.”
Last Updated February 03, 2021
Gill disclosed support from the Canadian Institutes of Health Research and relevant relationships with Astellas Pharma. Co-authors disclosed relevant relationships with, and/or support from, Astellas Pharma and Sanofi.
Matas disclosed no relevant relationships with industry.