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.