Abstract | BACKGROUND:
Hypercalciuria is the most common metabolic abnormality observed in patients with nephrolithiasis. Hypercalciuria raises urine supersaturation with respect to the solid phases of calcium oxalate and calcium phosphate, leading to an enhanced probability for nucleation and growth of crystals into clinically significant stones. However, there is little direct proof that supersaturation itself regulates stone formation. Through successive inbreeding of the most hypercalciuric progeny of hypercalciuric Sprague-Dawley rats, we have established a strain of rats, each of which excrete abnormally large amounts of urinary calcium and each of which forms calcium phosphate kidney stones. We used these hypercalciuric (GHS) rats to test the hypothesis that an isolated reduction in urine supersaturation, achieved by decreasing urine phosphorus excretion, would decrease stone formation in these rats. METHODS: Thirty 44th-generation female GHS rats were randomly divided into three groups. Ten rats received a high- phosphorus diet (0.565% phosphorus), 10 a medium- phosphorus diet (0.395% phosphorus), and 10 a low- phosphorus diet (0.225% phosphorus) for a total of 18 weeks. The lowered dietary phosphorus would be expected to result in a decrease in urine phosphorus excretion and a decrease in urinary supersaturation with respect to the calcium phosphate solid phase. Every two weeks, 24-hour urine collections were obtained. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate were determined. At the conclusion of the experiment, each rat was killed, and the kidneys, ureters, and bladder were dissected en block and x-rayed to determine whether any stones formed. A decrease in stone formation with a reduction in urinary supersaturation would support the hypothesis that supersaturation alone can regulate stone formation. RESULTS: CONCLUSIONS: A decrease in urine phosphorus excretion not only led to a decrease in urine supersaturation with respect to the calcium phosphate solid phase but to an elimination of renal stone formation. The results of this study support the hypothesis that variation in supersaturation alone can regulate renal stone formation. Whether a reduction of dietary phosphorus will alter stone formation in humans with calcium phosphate nephrolithiasis remains to be determined.
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Authors | D A Bushinsky, W R Parker, J R Asplin |
Journal | Kidney international
(Kidney Int)
Vol. 57
Issue 2
Pg. 550-60
(Feb 2000)
ISSN: 0085-2538 [Print] United States |
PMID | 10652032
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Calcium Phosphates
- Phosphorus, Dietary
- Quaternary Ammonium Compounds
- alpha-tricalcium phosphate
- tetracalcium phosphate
- Calcium Oxalate
- Citric Acid
- calcium phosphate, monobasic, anhydrous
- calcium phosphate
- calcium phosphate, dibasic, anhydrous
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Topics |
- Animals
- Calcium Oxalate
(urine)
- Calcium Phosphates
(urine)
- Citric Acid
(urine)
- Diet
- Female
- Hydrogen-Ion Concentration
- Kidney
(diagnostic imaging)
- Kidney Calculi
(diet therapy, genetics, metabolism)
- Male
- Phosphorus, Dietary
(metabolism, pharmacology)
- Quaternary Ammonium Compounds
(urine)
- Radiography
- Rats
- Rats, Sprague-Dawley
- Solubility
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