Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment

Ruangyuttikarn, Werawan; Panyamoon, Amnart; Nambunmee, Kowit; Honda, Ryumon; Swaddiwudhipong, Witaya; Nishijo, Muneko

doi:10.1186/2193-1801-2-533

Cited by 40 publications

(34 citation statements)

References 34 publications

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“…Chronic KIM-1 induction however, has been shown to be maladaptive and promotes fibrosis (Ferenbach and Bonventre, 2015) and this correlates with the persistent induction and excretion of KIM-1 in variety of inflammatory and fibrotic pathogeneses in the kidney (van Timmeren et al , 2007). In environmental settings, KIM-1 has demonstrated to be more sensitive than N-acetyl-β- d -glucosaminidase and β2 microglobulin for the detection of kidney injury induced by chronic cadmium exposure (Prozialeck et al, 2007; Ruangyuttikarn et al , 2013). We found that KIM-1, among all the biomarkers examined, was most strongly associated with chromium and arsenic exposure.…”

Section: Discussionmentioning

confidence: 99%

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Cárdenas-González

Osorio-Yáñez

Gaspar-Ramírez³

et al. 2016

Environmental Research

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Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of environmental kidney toxicants exposure and kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μL) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker for environmental exposure risk assessment and kidney toxicity in children.

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Section: Discussionmentioning

confidence: 99%

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Cárdenas-González

Osorio-Yáñez

Gaspar-Ramírez³

et al. 2016

Environmental Research

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“…Currently, KIM-1 has become one of the key biomarkers for diagnosis, disease activity monitoring and prognosis of acute kidney injury29303132. There is evidence suggesting that KIM-1 can be used for early screening and diagnosis of renal injury induced by cadmium poisoning333435. However, no clinical data is available assessing the correlation of urinary KIM-1 with lead-induced renal damage.…”

Section: Discussionmentioning

confidence: 99%

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Zhou

Shen

et al. 2016

Sci Rep

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Chronic occult lead poisoning often develops ensuing occupational lead exposure. Early diagnosis of lead poisoning is critical for timely discontinuation of lead exposure and for prognosis. This study explored the value of urinary kidney injury molecule-1 (KIM-1) in diagnosing renal injury induced by lead at an early stage. We retrospectively analyzed 92 workers exposed to occupational lead and demonstrated a better correlation ship between blood lead levels and urine excretion of KIM-1 than other traditional renal injury biomarkers following creatinine adjustment. Receiver operating characteristic curve analysis of the ability of diverse biomarkers for predicting kidney injury in lead-exposed workers demonstrated that the order of predicting accuracy of the studied biomarkers is as follows: urinary KIM-1-to-creatinine ratio > urinary N-acetyl-β-(D)-glucosaminidase-to-creatinine ratio > urinary β2-microglobulin-to-creatinine ratio > urinary α1-microglobulin-to-creatinine ratio, with the Youden index being 16.59 ng/g, 14.01 U/g, 0.15 mg/g, and 4.63 mg/g, respectively. Collectively, our findings suggest that short-period occupational lead exposure may cause injury of renal tubules. Urinary excretion of KIM-1 correlates with blood lead levels better than other traditional renal injury biomarkers, including N-acetyl-β-(D)-glucosaminidase, α1-microglobulin, and β2-microglobulin. Longitudinal surveillance of urinary KIM-1 may aid for early diagnosis of renal tubular injury in workers with occupational lead exposure.

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“…The subjects in the polluted area were participants aged ≥ 40 years in the 2007 health survey (participant rate 83.7%) targeted for residents whose urinary Cd levels were ≥5 μg/g Creat in 2004–5 [25,26]. The numbers of subjects in the non-polluted area was small, which is a serious limitation of this study, but addition of these subjects in the non-polluted area increased the low rate of subjects with urinary Cd < 5 μg/g Creat in the polluted area.…”

Section: Methodsmentioning

confidence: 99%

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

et al. 2014

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BackgroundThe aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population.MethodsThe study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status.ResultsThe estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary β2-MG and 4.4 for NAG in men and 8.1 for β2-MG and 6.1 for NAG μg/g creatinine (Creat) in women. These BMDLs of urinary Cd (μg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (μg/L) were 6.2 for urinary β2-MG and 5.0 for NAG in men and 5.9 for β2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (μg/L) in the polluted Thai area (6.9 in men and 5.2 in women).ConclusionThe BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4 - 8.1 μg/g Creat and 4.4 - 6.2 μg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

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Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment

Cited by 40 publications

References 34 publications

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand

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