Steroid-sparing regimens lower risk of diabetes mellitus after transplant in some adults
Steroid avoidance can lower the risk of diabetes mellitus after transplant in older patients or those who have higher BMIs when paired with appropriate induction regimens, according to data published in Kidney Medicine.
Previous studies have explored the risk of posttransplant diabetes mellitus (PTDM), but few have evaluated the benefit of alternative immunosuppression strategies such as steroid avoidance to lower the risk of PTDM among older patients and obese patients.
“Despite the growing number of older kidney transplant recipients, older adults continue to be underrepresented in transplant clinical trials,” Krista L. Lentine, MD, PhD, a professor at Saint Louis University Center for Abdominal Transplantation, told Healio. “To strengthen the evidence for tailored immunosuppression choice, our research team has been working on observational studies of the impact of early immunosuppression regimen selection (induction and maintenance) on outcomes in a national cohort of U.S. transplant recipients, with sufficient sample size to adjust for potential confounding effects including donor characteristics.”
In a retrospective database study, researchers investigated the correlation of immunosuppression regimen with PTDM, while focusing on groups sensitive to PTDM such as older adults and patients with increased BMI. Patients in this study were aged 18 or older and were included in the U.S. Renal Data System between 2005 to 2016. All participants had Medicare.
In collaboration with David A. Axelrod, MD, MBA, and Wisit Cheungpasitporn, MD, Lentine and colleagues identified the use of induction agents and early immunosuppression regimen based on Medicare pharmacy claims for immunosuppression agents submitted within the first 3 months following transplant. Patients were then separated into seven regimens based on induction and maintenance immunosuppression regimens.
Using multivariable Cox regression, researchers compared the incidence of PTDM by immunosuppression regiment with the reference regiment thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus, mycophenolic acid and prednisone using inverse propensity weighting. The primary outcome was the development of PTDM.
Researchers found 12.7% of kidney transplant recipients developed PTDM, with higher incidences in older (55 years vs. <55 years: 16.7% vs. 10.1%) and obese (BMI 30 kg/m² vs. <30 kg/m²: 17.1% vs. 10.9%) patients. The occurrence of PTDM was lower with steroid avoidance. The occurrence was 8.4% for TMG/ALEM without prednisone and 9.7% for IL-2 receptor antibody (IL2rAb) without prednisone vs. 13.1% for TMG/ALEM with triple therapy.
While TMG/ALEM with steroid avoidance was beneficial for all groups after adjusting for donor and recipient characteristics, IL2rAb with steroid avoidance was only beneficial for older patients (adjusted HR, 0.76), and those with a BMI of less than 30 kg/m2 (aHR, 0.63).
“This study of a large, contemporary sample of kidney transplant patients identified an overall benefit of steroid-sparing regimens accompanied by appropriate induction (either TMG or ALEM) among older adults, after adjusting for comorbidities (eg, Hepatitis C) and patients characteristics (eg, race/ethnicity),” Lentine told Healio. “By comparison, younger and obese patients derive a benefit from steroid avoidance regimens, but only if the risk of rejection is mitigated by T-cell depleting induction (TMG/ALEM).”
Lentine noted, “These data support efforts to personalize the immunosuppressive regimen according to recipient and donor characteristics and limit exposure to more intense immunosuppressive regimens, when possible, to reduce the risk of complications.”