title: Deleterious role of trace elements - Silica and lead in the development of chronic kidney disease.
abstract: Chronic-Kidney-Disease of Unknown-etiology (CKDu) has been reported in developing-countries like Sri-Lanka, India and Central-America without sparing the Indian sub-district (namely Canacona) located in south-Goa. The disease etiology is unlinked to common causes of diabetes and hypertension and assumed to be environmentally induced due to its asymptomatic-nature and occurrence in groundwater relying communities. This study aimed to understand environmental risk-factors underlying CKDu-etiology using Indian sub-district (Canacona) as case-study. Biochemical-analysis of CKDu-affected and non-affected individual's blood and detailed hydro-geochemical analyses of CKDu-affected and non-affected region's groundwater (drinking-water)were conducted. Trace geogenic-element-silica was highly dominant in affected-region's groundwater, thus its nephrotoxic-potential was analysed via in-vitro cytotoxicity-assays on human-kidney-cell-lines. All CKDu-affected-subjects showed increased-levels of serum-urea (52.85 mM),creatinine (941.5 μM),uric-acid (1384.5 μM), normal blood-glucose (4.65 mM), being distinct biomarkers of environmentally-induced CKD-'chronic-tubulo-interstitial-nephritis'. Affected-subjects reported high blood-lead levels (1.48 μM)suggesting direct-nephrotoxicity resulting in impaired blood-clearance and also exhibits indirect-nephrotoxicity by disrupting calcium-homeostasis causing skeletal-disorders and prolonged-consumption of NSAID's (pain-alleviation), indirectly causing renal-damage. Affected-region's groundwater was acidic (pH-5.6), resulting in borderline-lead (9.98 μgL-1) and high-silica (115.5 mgL-1)contamination. Silica's bio-availability (determining its nephrotoxicity) was enhanced at groundwater's acidic-pH and Ca-Mg-deficient-composition (since these cations complex with silica reducing bioavailability). Silica exhibited renal-proximal-tubular-cytotoxicity on long-term exposure comparable with affected-region's groundwater silica-levels, by apoptosis-mediated-cell-death resulting in tubular-atrophy, interstitial-fibrosis and irreversible renal-damage (CKD). Thus this study provides novel-insights into nephrotoxic-potential of trace-geogenic-element-silica in CKDu causation. It highlights direct-indirect nephrotoxicity exhibited by lead at low-levels due to its bio-accumulative-capacity. Silica's nephrotoxic-potential can be considered when deciphering etiology of CKDu-problem in developing-countries (relying on groundwater).
authors.affiliation: Department of Biological Sciences, BITS Pilani, K K Birla Goa Campus, NH 17 B, Zuarinagar, Goa, 403 726, India. Electronic address: p2013402@goa.bits-pilani.ac.in.
authors.forename: Starlaine
authors.initials: S
authors.lastname: Mascarenhas
authors.affiliation: Department of Biological Sciences, BITS Pilani, K K Birla Goa Campus, NH 17 B, Zuarinagar, Goa, 403 726, India. Electronic address: srikanth@goa.bits-pilani.ac.in.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Mutnuri
authors.affiliation: Department of Biological Sciences, BITS Pilani, K K Birla Goa Campus, NH 17 B, Zuarinagar, Goa, 403 726, India. Electronic address: ganguly@goa.bits-pilani.ac.in.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Ganguly
mesh_terms: D000328:Adult; D000886:Anthropometry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003404:Creatinine / Q000097:blood; D060766:Drinking Water / Q000032:analysis*; D005260:Female; D060587:Groundwater / Q000032:analysis; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007194:India; D007854:Lead / Q000032:analysis* / Q000097:blood; D008297:Male; D008670:Metals / Q000737:chemistry; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000453:epidemiology; D012307:Risk Factors; D012822:Silicon Dioxide / Q000032:analysis*; D014131:Trace Elements / Q000032:analysis*; D014508:Urea / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D001786:Blood Glucose; D060766:Drinking Water; D008670:Metals; D014131:Trace Elements; D007854:Lead; D012822:Silicon Dioxide; D014508:Urea; D003404:Creatinine
keywords: CKDu; Emerging-contaminant-silica; Environmental-nephrotoxins; Groundwater; Lead; Trace-elements