Frailty, Immunosuppression Tolerance, and Outcomes in Kidney Transplant Recipients.

Abstract

Background: MMF dose reduction or discontinuation predicts poor KT outcomes including rejection, graft loss and death. However, little is known about which patients are at risk of MMF intolerance. Frailty, a measure of physiologic reserve initially described and validated in geriatrics, is emerging as an important predictor in kidney transplantation (KT) recipients of all ages, including early hospital readmission, delayed graft function, graft loss and mortality. We hypothesized that frailty, given its association with an inflammatory phenotype, might also predict MMF immunosuppression tolerance. Methods: We measured frailty (shrinking, weakness, exhaustion, low activity, and slowed walking speed) in KT recipients at admission for KT. Frailty and MMF dose was available for 535 KT recipients. MMF intolerance (MMF dose reduction <2000 mg/day) was identified from electronic medical records. The risk of MMF intolerance by frailty status was quantified using Cox proportional hazards model that censored for death and adjusted for multiple recipient, donor, and transplant factors. Results: 46% of recipients were non-frail (0 or 1 component), 32% were intermediately frail (2 components), and 22% were frail at KT (3 or more components). The mean follow-up time was 1.5 years [IQR: 0.4-2.3 years] and 52.9% of recipients had an MMF reduction. Compared to those who were non-frail, intermediately or frail recipients were at 35% higher risk of MMF immunosuppression intolerance (adjusted hazard ratio 1.35, 95% CI: 1.06-1.71). The association of frailty and MMF immunosuppression intolerance did not differ by recipient age (P for interaction=0.8). Conclusion: Intermediately frail and frail KT recipients are at increased risk of MMF immunosuppression intolerance. It is possible that this intolerance partially explains why these recipients are at increased risk of poor KT outcomes such as graft loss and mortality. A better understanding of which patients might not tolerate MMF is helpful in planning alternate strategies to maintain adequate immunosuppression.