Abstract

Introduction: Serum uric acid is positively associated with serum glucose in healthy subjects, and prospective epidemological studies have shown that elevated serum uric acid is associated with increased risk of incident type 2 diabetes. We hypothesized that, in kidney transplant recipients (KTR), serum uric acid is independently associated with increased risk of posttransplantation diabetes mellitus (PTDM). Methods: We performed a longitudinal cohort study of 524 adult KTR with a functioning graft for at least 1 year, recruited at a university setting (2008-2011). PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. A Kaplan-Meier curve, log-rank test, and multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of serum uric acid with PTDM. Results: Mean (standard deviation) serum uric acid was 0.42 (0.11) mmol/L. During 5.3 (IQR, 4.1‒6.0) years of follow-up, 52 (10%) KTR developed PTDM, with a significantly higher incidence of events across increasing tertiles of serum uric acid distribution (Log-rank test, P=0.02). In Cox regression analyses, serum uric acid was associated with increased risk of PTDM (HR 3.00, 95% CI 1.42‒6.36 per log2 mmol/L; P=0.004). Our findings were independent of adjustment for components of the metabolic syndrome, i.e., waist circumference, fasting plasma glucose, glycated hemoglobin, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and antihypertensive medication (adjusted HR 2.74, 95% CI 1.19‒6.35 per log2 mmol/L; P=0.018). Our findings were robust in further analyses with adjustment for donor and transplant characteristics. Furthermore, these results remained materially unchanged in sensitivity analyses with serum uric acid as categorical variable and with removal of all outliers (adjusted HR of 2.17, 95% CI 1.03‒4.61; P=0.04; for patients in tertile 3 of serum uric acid distribution). Conclusions: In stable KTR, relatively higher serum uric acid levels are strongly and independently associated with increased risk of PTDM. These findings are in agreement with accumulating evidence that supports serum uric acid as a novel risk factor for type 2 diabetes, and extend those findings, for the first time, to the post-kidney transplantation setting. External validation studies are warranted to confirm our results and investigate the performance and potential clinical application of serum uric acid in the evaluation of risk of PTDM.