Abstract

Cadmium (Cd) has been found as an environmental pollutant in Mae Sot district, Tak province, Thailand. Prolong exposure to high levels of Cd of the resident increases high risk of Cd toxicity especially to kidney which is the primary target of Cd. In order to investigate the early effect of Cd induced renal dysfunction, a kidney injury molecule-1 (KIM-1), a novel biomarker of renal tubular dysfunction, was measured using an enzyme linked immunosorbent assay (ELISA). The method was validated and used to quantify the KIM-1 concentrations in the urine of 700 subjects (260 men, 440 women) who lived in the Cd contaminated area. The KIM-1 concentrations were compared to the concentrations of two conventional renal tubular dysfunction biomarkers, N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin (β2-MG). Urinary KIM-1 was correlated with urinary and blood Cd as well as NAG. After adjustment of age and smoking, urinary KIM-1 was correlated with blood Cd more than urinary NAG did. Clear dose response relationships of urinary KIM-1 with urinary Cd were shown in both men and women. These results indicate that the urinary KIM-1 might be more sensitive biomarker than urinary NAG and β2-MG for an early detection of renal tubular dysfunction. It is useful as a tool to detect renal effect of toxicity due to chronic Cd exposure at high level.

Highlights

  • kidney injury molecule-1 (KIM-1) is a type 1 cell membrane glycoprotein containing six-cysteine immunoglobulin-like and mucin domains (Ichimura et al 1998)

  • Cd is an important industrial and environmental pollutant that adversely affects multiple organ systems (WHO 1992; Jarup et al 1998), of which the kidney is the primary target in humans with chronic Cd exposure (Friberg 1984; Lauwerys et al 1984; Jarup et al 1998)

  • We report here a use of the KIM-1 as a sensitive biomarker for early detection of renal tubular dysfunction in Mae Sot residents with high Cd exposure and compared its prevalence with those of two conventional renal biomarkers, NAG and β2-MG concentrations to show usefulness of KIM-1 measurement among Cd exposed population at high level

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Summary

Introduction

KIM-1 is a type 1 cell membrane glycoprotein containing six-cysteine immunoglobulin-like and mucin domains (Ichimura et al 1998) It has been reported as an undetectable biomarker in normal urine but after kidney injury is expressed at high levels (Ichimura et al 2004; Vaidya et al 2008; Ferguson et al 2008). Elevated KIM-1 level was found in human renal diseases associated with renal fibrosis, inflammation and dysfunction (van Timmeren et al 2007). It was proposed as an early indicator of acute kidney injury over the conventional biomarker such as blood urea nitrogen, serum creatinine (Cr), urinary albumin, low molecular weight excreted. Itai-itai disease was the most severe manifestation of cadmium toxicity in patients documented in Japan who suffered chronic exposure to high cadmium concentrations in contaminated water and rice (Nogawa et al 1987; Aoshima et al 1988)

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