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


CONCLUSIONS
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.
Amanzadeh
Jamshid
J
Center for Mineral Metabolism and Clinical Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8885, USA.
Gitomer
William L
WL
Zerwekh
Joseph E
JE
Preisig
Patricia A
PA
Moe
Orson W
OW
Pak
Charles Y C
CY
Levi
Moshe
M
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000473:pathology; D002118:Calcium / Q000097:blood / Q000652:urine; D002364:Caseins / Q000008:administration & dosage*; D003404:Creatinine / Q000378:metabolism; D029382:Dicarboxylic Acid Transporters / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage*; D007669:Kidney Calculi / Q000209:etiology*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D027981:Symporters / Q000378:metabolism
D002364:Caseins; D029382:Dicarboxylic Acid Transporters; D004044:Dietary Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; C490478:Slc13a2 protein, rat; D027981:Symporters; D003404:Creatinine; D002118:Calcium