Body mass index, weight-adjusted immunosuppression and the risk of acute rejection and infection after kidney transplantation: a cohort study

BACKGROUND: Body mass index (BMI) is associated with patient outcomes after kidney transplantation. We hypothesized that immunosuppression (IS) dosing is a contributing factor. METHODS: Using Australia and New Zealand Dialysis and Transplant registry data, we included all adult kidney-only transplant recipients over 2000-14 treated with prednisolone, mycophenolate and tacrolimus/cyclosporin (n = 7919). The exposure was BMI and the outcomes were time to: (i) acute rejection, (ii) fatal infection, (iii) cancer and (iv) graft; and (v) patient survival. We modelled BMI and IS dosing (in quartiles) as time-varying covariates in extended Cox models. RESULTS: Compared with a BMI of 25 kg/m2, a BMI of 35 was associated with acute rejection after adjusting for demographics and comorbidities [adjusted hazard ratio (aHR) = 1.29, 95% confidence interval (CI) 1.12-1.49]. This association virtually disappeared after correcting for IS (aHR = 1.09, 95% CI 0.93-1.29). A BMI of 35 was non-significantly associated with fewer fatal infections (aHR = 0.91, 95% CI 0.66-1.25), but this reversed after adjusting for IS (aHR = 1.54, 95% CI 1.03-2.28). Results for cancer were not significantly altered after adjusting for IS. Results for lower BMI were similarly not significantly altered though generally associated with worse outcomes. CONCLUSIONS: Our findings show that the associations between high BMI, acute rejection and fatal infection after kidney transplantation were significantly altered after correcting for IS suggesting that relative under-dosing of obese patients may partially explain these associations.