Circulating Arsenic is Associated with Long-Term Risk of Graft Failure in Kidney Transplant Recipients: A Prospective Cohort Study

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.

Plasma Vitamin B12 and Folate Alter the Association of Blood Lead and Cadmium and Total Urinary Arsenic Levels with Chronic Kidney Disease in a Taiwanese Population

“…One study did not find an association between the blood lead level and kidney function [25]. However, a cohort study found that plasma arsenic was associated with an increased risk of kidney graft failure [26]. A Thai study showed that long-term exposure to a low cadmium level was associated with decreased renal function [27].…”

Plasma Lead Concentration and Risk of Late Kidney Allograft Failure: Findings From the TransplantLines Biobank and Cohort Studies

“…6 In recent studies, we have shown that plasma cadmium (Cd) and arsenic (As) levels are each associated with increased risk of graft failure in kidney transplant recipients (KTR). 7,8 Another toxic heavy metal, lead (Pb), can be found in construction sites, paint, children's jewelry, folk remedies, glazed pottery, and even candy. 9 While occupational exposure is especially relevant in developing countries, 10 in developed countries, such as The Netherlands, significant amounts of Pb can be found in topsoil from construction works, disposal of coal ashes and fertilization of land with city waste, from where it can end up in food.…”

“…Whole blood and plasma Pb concentrations were determined with use of an inductively coupled plasma mass spectrometer (ICP-MS, Varian 820-MS; Varian, Palo Alto, USA) with a validated J o u r n a l P r e -p r o o f method for the measurement of heavy metals, as previously reported. 7,8 Standards were made by addition to blank blood or plasma of known amounts of Pb to obtain added concentrations of: 2,5; 5; 10; 15; 20 and 25 µg/L. Control samples were made by spiking blank blood or plasma with known amounts of Pb to obtain added concentrations of respectively: 7.5 (low); 25.0 (medium) and 45.0 µg/L (high).…”

Plasma cadmium is associated with increased risk of long-term kidney graft failure

“…As described elsewhere, 72 dietary intake was assessed using a 177food item-validated semiquantitative food frequency questionnaire developed and updated at Wageningen University. 69 Further information on the food frequency questionnaire can be found in the Supplementary Methods.…”