title: Creatinine, arsenic metabolism, and renal function in an arsenic-exposed population in Bangladesh.
abstract: Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Consistent with renal toxicity of As, log-uAs had a marginal inverse association with eGFR in the 2003 sample (b = -5.6, p = 0.07), however this association was not significant in the 2001 sample (b = -1.9, p = 0.24). Adjustment for eGFR did not alter the associations between uCrn and the %uAs metabolites, indicating that GFR does not explain these associations. Increased eGFR was associated with increased odds of having %uInAs >12.2% (2001: OR = 1.01, 95%CI (1.00,1.03); 2003: OR = 1.04, 95%CI (1.01,1.07)). In the 2003 sample only, there was a negative association between eGFR and %uDMA (b = -0.08, p = 0.02). These results may indicate differential effects of renal function on excretion of InAs and DMA. Alternatively, a certain methylation pattern, involving decreased %InAs and increased %DMA, may reduce renal function. Given that these studies were cross-sectional, we cannot distinguish between these two possibilities. Discrepancies between the samples may be due to the higher As exposure, poorer nutrition, and lower As methylation capacity in the 2003 sample.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Brandilyn A
authors.initials: BA
authors.lastname: Peters
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Y Dana
authors.initials: YD
authors.lastname: Neugut
authors.affiliation: Division of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Pilsner
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Pam
authors.initials: P
authors.lastname: Factor-Litvak
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000293:Adolescent; D000328:Adult; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D001459:Bangladesh; D003404:Creatinine / Q000652:urine*; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000652:urine; D008297:Male; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000737:chemistry; D055815:Young Adult
chemical_list: D014874:Water Pollutants, Chemical; D012436:S-Adenosylmethionine; D003404:Creatinine; D001151:Arsenic