Immunosuppression in Older Adult Transplants

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Older adult kidney transplant recipients may benefit from lower-intensity, steroid-sparing immunosuppression regimens that better take into account recipient and donor characteristics, according to a nationwide database study in Transplantation.

The percentage of kidney transplants in older adults has increased dramatically in recent years, yet immunosuppressive management in this age group is challenging and little evidence exists to guide clinical decision-making.

With the use of data from the US Renal Data System, the researchers identified 67,632 patients with Medicare claims for immunosuppression after kidney transplantation in 2015−2016. Induction and maintenance immunosuppressive drugs were classified into seven regimens and analyzed for associations with acute rejection, graft failure, and mortality. The findings for older adults (age 65 or older) and younger adults were assessed by multivariable regression analysis.

Older adult kidney transplant recipients were less likely to receive anti-thymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (the reference regimen): 36.9% compared to 47.0% in younger adults. Older adults were also less likely to receive TMG/ALEM plus steroid avoidance, 19.2% vs. 20.1%; mammalian target of rapamycin inhibitor (mTORi)-based regimens, 6.7% vs. 7.7%. In contrast, patients aged 65 or older were more likely to receive interleukin-2-receptor antibody (IL2rAb) plus triple maintenance, 21.1% vs. 14.7%; IL2rAb plus steroid avoidance, 4.1% vs. 1.8%; and cyclosporine-based immunosuppression, 8.3% vs. 6.6%.

Compared to TMG/ALEM plus triple maintenance, steroid-sparing immunosuppressive regimens were associated with a lower risk of acute rejection in older adults: adjusted odds ratio 0.52 with TMG/ALEM plus steroid avoidance and 0.55 with IL2rAb plus steroid avoidance. Compared to the reference regimen, risk of death-censored graft failure was higher for older adults receiving tacrolimus plus antimetabolite avoidance, adjusted hazard ratio (HR) 1.78; mTORi-based immunosuppression, HR 2.14; and cyclosporine-based regimens, HR 1.78. In both age groups, mTORi- and cyclosporine-based regimens were associated with higher mortality: HR 1.24 and 1.37 in older recipients and 1.35 and 1.24 in younger recipients, respectively.

The new study provides insights into trends in immunosuppressive regimens for older adult kidney recipients, including associations with clinical outcomes. “These data support the move to further personalize the immunosuppressive regimen according to recipient and donor characteristics and limit exposure to more intense immunosuppressive regimens,” the researchers write [Lentine KL, et al. Immunosuppression regimen use and outcomes in older and younger adult kidney transplant recipients: A National Registry analysis. Transplantation, published online ahead of print November 18, 2020. doi: 10.1097/TP.0000000000003547; ].