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Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis

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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.

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Acknowledgements

The Urological Society from Madrid, SUM Research Grant 2013 and Astellas Pharma España are acknowledged.

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Authors and Affiliations

  1. Department of Urology, Hospital Universitario Puerta de Hierro-Majadahonda, C/Lope de Vega 2, portal 5 1ºB, Pozuelo de Alarcón, 28223, Madrid, Spain

    Javier Sáenz-Medina, I. Castillón & J. Carballido

  2. Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain

    E. Jorge, P. Soblechero & E. Virumbrales

  3. Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain

    C. Corbacho

  4. Medical and Surgical Research Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain

    M. Santos

  5. Biobank, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain

    A. Sánchez

  6. Molecular Biology and DNA Sequencing Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain

    E. Ramil

  7. Confocal Microscopy Facility, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain

    M. J. Coronado

  8. Department of Animal Phisiology, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

    D. Prieto

Authors
  1. Javier Sáenz-Medina
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  2. E. Jorge
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  3. C. Corbacho
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  4. M. Santos
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  5. A. Sánchez
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  6. P. Soblechero
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  7. E. Virumbrales
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  8. E. Ramil
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  9. M. J. Coronado
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  10. I. Castillón
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  11. D. Prieto
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  12. J. Carballido
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Corresponding author

Correspondence to Javier Sáenz-Medina.

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Funding

Urological Society from Madrid. Research Grant 2013 and Astellas Pharma España are acknowledged.

Conflict of interest

Sáenz-Medina J., Jorge E., Corbacho C., Santos M., Sánchez A., Soblechero P., Virumbrales E., Ramil E., Coronado M.J., Castillón I., Carballido J. declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Sáenz-Medina, J., Jorge, E., Corbacho, C. et al. Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis. Urolithiasis 46, 179–186 (2018). https://doi.org/10.1007/s00240-017-0979-9

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  • DOI: https://doi.org/10.1007/s00240-017-0979-9

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