Effect of high protein diet on stone-forming propensity and bone loss in rats

Jamshid Amanzadeh, William L. Gitomer, Joseph E. Zerwekh, Patricia A. Preisig, Orson W. Moe, Charles Y C Pak, Moshe Levi

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Background. High protein diets are believed to cause kidney stone formation and bone loss, but the mechanisms mediating these changes are unknown. The purpose of this study was to create an animal model of animal protein excess and to evaluate the response of kidney and bone to the dietary protein load. Methods. Rats (12 per group) were pair-fed with a high (48%) and low (12%) casein diets that were otherwise identical in their content of sodium, potassium, calcium, phosphorus, and magnesium. Results. Compared with the low casein group, the high casein group delivered a substantial acid load during 59 days of study, since it significantly decreased urinary pH, and increased urinary ammonium, titratable acidity, and net acid excretion. Animals on high casein diet also had higher urinary volumes. On the high casein diet, urinary calcium excretion was significantly higher and urinary citrate excretion and concentration was significantly lower. On the high casein diet, urinary saturation of calcium phosphate was higher. Serum calcitriol concentration did not significantly differ between the two groups. Histomorphometric analysis of femur procured after 59 days on the diet showed marked increase in bone resorption in the high casein group. Hypocitraturia was associated with increased activity of sodium-citrate cotransporter in renal cortical brush-border membranes (BBM) in the high casein group. Conclusion. Both the kidney and bone contribute to the pathogenesis of hypercalciuria during high casein diet in rats. Hypocitraturia is probably renal in origin. This rat model will be useful in elucidating the mechanisms by which high protein intake increases the risk of nephrolithiasis and bone loss in human beings.

Original languageEnglish (US)
Pages (from-to)2142-2149
Number of pages8
JournalKidney international
Issue number6
StatePublished - Dec 2003


  • Animal protein
  • Bone loss
  • Hypercalciuria
  • Hypocitraturia
  • Nephrolithiasis

ASJC Scopus subject areas

  • Nephrology


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