Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Estimation of the Cadmium Nephrotoxicity Threshold from Loss of GFR and Albuminuria

Version 1 : Received: 17 August 2023 / Approved: 17 August 2023 / Online: 17 August 2023 (08:07:45 CEST)

A peer-reviewed article of this Preprint also exists.

Satarug, S.; Vesey, D.A.; Khamphaya, T.; Pouyfung, P.; Gobe, G.C.; Yimthiang, S. Estimation of the Cadmium Nephrotoxicity Threshold from Loss of Glomerular Filtration Rate and Albuminuria. Toxics 2023, 11, 755. Satarug, S.; Vesey, D.A.; Khamphaya, T.; Pouyfung, P.; Gobe, G.C.; Yimthiang, S. Estimation of the Cadmium Nephrotoxicity Threshold from Loss of Glomerular Filtration Rate and Albuminuria. Toxics 2023, 11, 755.

Abstract

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to progress loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) in according to levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria, (Ealb/Ccr)×100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) ×100 < 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (β = 0.007), while an inverse association with ECd/Ccr was found in the medium (β =−0.230) and high-burden groups (β =−0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132), but did not with low tertile (η2 0.001). With adjustment of eGFR, age and BMI, POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data argue that ECd/Ccr of 1.44 µg/L filtrate (0.01−0.02 µg/g creatinine) could determine a Cd threshold level from which protective exposure guidelines should be formulated.

Keywords

albuminuria; blood pressure; cadmium; chronic kidney disease; estimated GFR

Subject

Public Health and Healthcare, Public, Environmental and Occupational Health

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