Abstract
Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ. We aimed to investigate whether, in kidney transplant recipients (KTRs), the nephrotoxic exposure to arsenic could represent an overlooked hazard for graft survival. We performed a prospective cohort study of 665 KTRs with a functional graft ≥1 year, recruited in a university setting (2008‒2011), in The Netherlands. Plasma arsenic was measured by ICP-MS, and dietary intake was comprehensively assessed using a validated 177-item food-frequency questionnaire. The endpoint graft failure was defined as restart of dialysis or re-transplantation. Median arsenic concentration was 1.26 (IQR, 1.04‒2.04) µg/L. In backwards linear regression analyses we found that fish consumption (std β = 0.26; p < 0.001) was the major independent determinant of plasma arsenic. During 5 years of follow-up, 72 KTRs developed graft failure. In Cox proportional-hazards regression analyses, we found that arsenic was associated with increased risk of graft failure (HR 1.80; 95% CI 1.28–2.53; p = 0.001). This association remained materially unaltered after adjustment for donor and recipient characteristics, immunosuppressive therapy, eGFR, primary renal disease, and proteinuria. In conclusion, in KTRs, plasma arsenic is independently associated with increased risk of late graft failure.
Highlights
Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ [1,2]
Arsenic induces morphological alterations of mitochondria that lead to uncontrolled formation of free radicals [4], whilst it inhibits the production of glutathione that protects cells from oxidative damage, yielding irreversible cell damage [5,6]
If analyses were performed with estimated glomerular filtration rate (eGFR) excluded from the initial model, fish consumption (β = 0.27; p < 0.001) was identified as the only independent determinant of arsenic (Table 2)
Summary
Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ [1,2]. Free radical mediated-oxidative damage is the cornerstone of arsenic-induced pathology [3]. Arsenic induces morphological alterations of mitochondria that lead to uncontrolled formation of free radicals [4], whilst it inhibits the production of glutathione that protects cells from oxidative damage, yielding irreversible cell damage [5,6]. Seafood is thought to be a major route for arsenic intake, followed by alcohol consumption, with the latter mainly due to contaminated wine, therewith representing an evident public health threat [20,21]
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