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      Drinking water heavy metal toxicity and chronic kidney diseases: a systematic review

      1 , 2 , 1 , 2 , 1 , 3 , 3 , 1 , 4
      Reviews on Environmental Health
      Walter de Gruyter GmbH

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          Abstract

          Heavy metals in drinking water can threat human health and may induce several diseases. The association between heavy metals exposure and chronic kidney disease (CKD) has been indicated by few epidemiological studies. We conducted a systematic review of the epidemiologic publications of the association between exposure to heavy metals through drinking water and CKD. Keywords related to heavy metals and kidney diseases on MeSH were identified and searched in PubMed, Google Scholar, Scopus, Ovid-Medline and Web of Science until July 2020. 14 publications met our inclusion criteria and included in the current review. The included articles were conducted on the association between arsenic, cadmium, lead and chromium in drinking water and CKD. Our study could not find strong evidence between heavy exposure to through drinking water and CKD, except for arsenic. The negative association was found between arsenic and lead and glomerular filtration rate (eGFR). The positive correlation was observed between cadmium exposure and urinary N-acetyl- β- d-glucosaminidase (NAG) concentrations, and also arsenic and chromium exposure and kidney injury molecule (KIM-1). Assessment of studies showed an association between arsenic, cadmium, lead and chromium and albuminuria and proteinuria, without CKD outcomes. Current systematic study showed few evidence for exposure to arsenic, cadmium, lead and chromium through drinking water and incidence of kidney problems. However, more epidemiological studies are required to confirm this association.

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          Most cited references40

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          Chronic kidney disease

          Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life, and require diagnosis and treatment.
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            Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury.

            Traditional blood and urine markers for the diagnosis of various renal diseases are insensitive and nonspecific. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein, with an immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. The ectodomain of KIM-1 is shed from cells. The current studies were carried out to evaluate whether KIM-1 is present in human acute renal failure and might serve as a urinary marker of acute renal tubular injury. Kidney tissue samples from six patients with biopsy-proven acute tubular necrosis (ATN) were evaluated by immunohistochemistry for expression of KIM-1. Urine samples were collected from an additional thirty-two patients with various acute and chronic renal diseases, as well as from eight normal controls. Urinary KIM-1 protein was detected by immunoassay and was quantified by ELISA. There was extensive expression of KIM-1 in proximal tubule cells in biopsies from 6 of 6 patients with confirmed ATN. The normalized urinary KIM-1 levels were significantly higher in patients with ischemic ATN (2.92 +/- 0.61; N = 7) compared to levels in patients with other forms of acute renal failure (0.63 +/- 0.17, P < 0.01; N = 16) or chronic renal disease (0.72 +/- 0.37, P < 0.01; N = 9). Adjusted for age, gender, length of time delay between the initial insult and sampling of the urine, a one-unit increase in normalized KIM-1 was associated with a greater than 12-fold (OR 12.4, 95% CI 1.2 to 119) risk for the presence of ATN. Concentrations of other urinary biomarkers, including total protein, gamma-glutamyltransferase, and alkaline phosphatase, did not correlate with clinical diagnostic groupings. A soluble form of human KIM-1 can be detected in the urine of patients with ATN and may serve as a useful biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator.
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              Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense.

              In tumor cell lines, multidrug resistance is often associated with an ATP-dependent decrease in cellular drug accumulation which is attributed to the overexpression of certain ATP-binding cassette (ABC) transporter proteins. ABC proteins that confer drug resistance include (but are not limited to) P-glycoprotein (gene symbol ABCB1), the multidrug resistance protein 1 (MRP1, gene symbol ABCC1), MRP2 (gene symbol ABCC2), and the breast cancer resistance protein (BCRP, gene symbol ABCG2). In addition to their role in drug resistance, there is substantial evidence that these efflux pumps have overlapping functions in tissue defense. Collectively, these proteins are capable of transporting a vast and chemically diverse array of toxicants including bulky lipophilic cationic, anionic, and neutrally charged drugs and toxins as well as conjugated organic anions that encompass dietary and environmental carcinogens, pesticides, metals, metalloids, and lipid peroxidation products. P-glycoprotein, MRP1, MRP2, and BCRP/ABCG2 are expressed in tissues important for absorption (e.g., lung and gut) and metabolism and elimination (liver and kidney). In addition, these transporters have an important role in maintaining the barrier function of sanctuary site tissues (e.g., blood-brain barrier, blood-cerebral spinal fluid barrier, blood-testis barrier and the maternal-fetal barrier or placenta). Thus, these ABC transporters are increasingly recognized for their ability to modulate the absorption, distribution, metabolism, excretion, and toxicity of xenobiotics. In this review, the role of these four ABC transporter proteins in protecting tissues from a variety of toxicants is discussed. Species variations in substrate specificity and tissue distribution of these transporters are also addressed since these properties have implications for in vivo models of toxicity used for drug discovery and development.
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                Author and article information

                Journal
                Reviews on Environmental Health
                Walter de Gruyter GmbH
                0048-7554
                2191-0308
                September 27 2021
                September 01 2021
                September 01 2021
                September 27 2021
                November 02 2020
                September 01 2021
                : 36
                : 3
                : 359-366
                Affiliations
                [1 ]Medical Toxicology and Drug Abuse Research Center (MTDRC) , Birjand University of Medical Sciences , Birjand , Iran
                [2 ]Faculty of Pharmacy, Birjand University of Medical Sciences , Birjand , Iran
                [3 ]Student Research Committee, Birjand University of Medical Sciences (BUMS) , Birjand , Iran
                [4 ]Department of Environmental Health Engineering, Faculty of Health , Birjand University of Medical Sciences, Birjand , Iran
                Article
                10.1515/reveh-2020-0110
                33128529
                0de973cb-a6a0-41e2-84db-f99378d6e938
                © 2021
                History

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