Abstract

Introduction: Arsenic exposure leads to nephrotoxicity, renal fibrosis, and progressive decline in renal function. To date, however, no study has been devoted to evaluate the association between arsenic exposure and renal allograft failure. We investigated the prospective association between circulating arsenic and risk of graft failure in a large cohort of renal transplant recipients (RTRs) with long-term follow-up. Methods: Blood arsenic concentrations were measured in an extensively phenotyped cohort of RTRs. Dietary intake was assessed using avalidated 177-item food Food Frequency Questionnaire. Backward linear regression analyses were performed to identify determinants of circulating arsenic concentrations. Associations of circulating arsenic concentrations with incident death-censored graft failure were assessed using Cox-proportional hazards regressions analyses. Results: We included 665 RTRs (53 � 13 years-old, 58% men). The median (interquartile range) arsenic concentration was 1.26 (1.04 - 2.04) ng/mL. Backward linear regression analyses showed that fish consumption and estimated Glomerular Filtration Rate (eGFR) were the major determinants of circulating arsenic concentrations (std. b = 0.22; P-value = 0.001; and, std. b = e0.19; P-value = 0.003, respectively). At 5 years of follow-up, 72 (11%) patients had developed graft failure. In multivariable Cox regression analyses, circulating arsenic was positively associated with risk of death-censored graft failure (hazard ratio, 1.59; 95% confidence interval, 1.10 to 2.30 per 1 ng/mL higher circulating arsenic concentration), independent of several potential confounders including transplant- and graft failure-related risk factors. Similar findings were found at 4 and 3 years of follow-up (respectively, hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; and, hazard ratio, 1.64; 95% confidence interval, 1.02 to 2.64, per 1 ng/mL higher circulating arsenic concentration). Conclusions: The association of post-transplant arsenic exposure with renal allograft outcomes has long been overlooked in clinical research. These data show for the first time that relatively higher post-transplant circulating arsenic concentrations are independently associated with higher long-term risk of graft failure in RTRs.