title: Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis.
abstract: Metabolic syndrome (MS) individuals have a higher risk of developing chronic kidney disease through unclear pathogenic mechanisms. MS has been also related with higher nephrolithiasis prevalence. To establish the influence of MS on renal function, we designed a murine model of combined metabolic syndrome and hyperoxaluria. Four groups of male Sprague-Dawley rats were established: (1) control group (n = 10) fed with standard chow; (2) stone former group (SF) (n = 10) fed with standard chow plus 0.75% ethylene glycol administered in the drinking water; (3) metabolic syndrome group (MS) (n = 10), fed with 60% fructose diet; (4) metabolic syndrome + stone former group (MS + SF) (n = 10), 60% fructose diet and 0.75% EG in the drinking water. MS group showed a significant injury to renal function when hyperoxaluria was induced. It was demonstrated by a significant decrease of creatinine clearance (p < 0.001), with higher tubular damage (34.3%, CI 95% 23.9-44.7, p < 0.001), produced by deposition of crystals, and increased tubular synthesis of osteopontin as a response to tubular damage. Induction of hyperoxaluria in rats with MS causes severe morphological alterations with a significant impairment of renal function. This impairment is not produced in rats without MS. Therefore, this model can be useful for the study of the influence of MS in stone formation.
authors.affiliation: Department of Urology, Hospital Universitario Puerta de Hierro-Majadahonda, C/Lope de Vega 2, portal 5 1ºB, Pozuelo de Alarcón, 28223, Madrid, Spain. javiersaenzmedina@yahoo.es.
authors.forename: Javier
authors.identifier: http://orcid.org/0000-0002-8568-854X
authors.initials: J
authors.lastname: Sáenz-Medina
authors.affiliation: Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Jorge
authors.affiliation: Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Corbacho
authors.affiliation: Medical and Surgical Research Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Santos
authors.affiliation: Biobank, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Soblechero
authors.affiliation: Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Virumbrales
authors.affiliation: Molecular Biology and DNA Sequencing Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ramil
authors.affiliation: Confocal Microscopy Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Coronado
authors.affiliation: Department of Urology, Hospital Universitario Puerta de Hierro-Majadahonda, C/Lope de Vega 2, portal 5 1ºB, Pozuelo de Alarcón, 28223, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Castillón
authors.affiliation: Department of Animal Phisiology, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Prieto
authors.affiliation: Department of Urology, Hospital Universitario Puerta de Hierro-Majadahonda, C/Lope de Vega 2, portal 5 1ºB, Pozuelo de Alarcón, 28223, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carballido
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism* / Q000652:urine; D003404:Creatinine; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects; D004195:Disease Models, Animal; D019855:Ethylene Glycol; D005632:Fructose; D006801:Humans; D006959:Hyperoxaluria / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000652:urine; D053040:Nephrolithiasis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000652:urine; D053495:Osteopontin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000652:urine
chemical_list: C506897:Spp1 protein, rat; D053495:Osteopontin; D002129:Calcium Oxalate; D005632:Fructose; D003404:Creatinine; D019855:Ethylene Glycol
keywords: Hyperoxaluria; Metabolic syndrome; Oxidative stress; Renal stone