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Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats.
J Am Soc Nephrol. 2005 Feb; 16(2):417-24.JA

Abstract

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.

Authors+Show Affiliations

Department of Medicine, University of Rochester School of Medicine and Dentistry, Strong Memorial Hospital, 601 Elmwood Avenue, Box 675, Rochester, NY 14642, USA. david_bushinsky@urmc.rochester.eduNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15647340

Citation

Bushinsky, David A., and John R. Asplin. "Thiazides Reduce Brushite, but Not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone-forming Rats." Journal of the American Society of Nephrology : JASN, vol. 16, no. 2, 2005, pp. 417-24.
Bushinsky DA, Asplin JR. Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats. J Am Soc Nephrol. 2005;16(2):417-24.
Bushinsky, D. A., & Asplin, J. R. (2005). Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats. Journal of the American Society of Nephrology : JASN, 16(2), 417-24.
Bushinsky DA, Asplin JR. Thiazides Reduce Brushite, but Not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone-forming Rats. J Am Soc Nephrol. 2005;16(2):417-24. PubMed PMID: 15647340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats. AU - Bushinsky,David A, AU - Asplin,John R, Y1 - 2005/01/12/ PY - 2005/1/14/pubmed PY - 2005/6/29/medline PY - 2005/1/14/entrez SP - 417 EP - 24 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 16 IS - 2 N2 - Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/15647340/Thiazides_reduce_brushite_but_not_calcium_oxalate_supersaturation_and_stone_formation_in_genetic_hypercalciuric_stone_forming_rats_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=15647340 DB - PRIME DP - Unbound Medicine ER -