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

Urolithiasis. 2018 Apr;46(2):179-186. doi: 10.1007/s00240-017-0979-9. Epub 2017 Apr 12.

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.

Keywords: Hyperoxaluria; Metabolic syndrome; Oxidative stress; Renal stone.

MeSH terms

  • Animals
  • Calcium Oxalate / metabolism*
  • Calcium Oxalate / urine
  • Creatinine
  • Diet, Carbohydrate Loading / adverse effects
  • Disease Models, Animal
  • Ethylene Glycol
  • Fructose
  • Humans
  • Hyperoxaluria / blood
  • Hyperoxaluria / etiology
  • Hyperoxaluria / metabolism*
  • Hyperoxaluria / urine
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / urine
  • Nephrolithiasis / blood
  • Nephrolithiasis / chemically induced
  • Nephrolithiasis / metabolism*
  • Nephrolithiasis / urine
  • Osteopontin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / blood
  • Renal Insufficiency / etiology
  • Renal Insufficiency / metabolism*
  • Renal Insufficiency / urine

Substances

  • Spp1 protein, rat
  • Osteopontin
  • Calcium Oxalate
  • Fructose
  • Creatinine
  • Ethylene Glycol