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Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.
J Am Soc Nephrol. 2019 07; 30(7):1163-1173.JA

Abstract

BACKGROUND

The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats.

METHODS

To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks.

RESULTS

Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not.

CONCLUSIONS

In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; Nancy_Krieger@URMC.Rochester.edu.Litholink Corporation, Laboratory Corporation of America Holdings, Chicago, Illinois.Litholink Corporation, Laboratory Corporation of America Holdings, Chicago, Illinois.Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.Department of Biostatistics and Computational Biology, University of Rochester School of Medicine, Rochester, New York; and.Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31101664

Citation

Krieger, Nancy S., et al. "Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats." Journal of the American Society of Nephrology : JASN, vol. 30, no. 7, 2019, pp. 1163-1173.
Krieger NS, Asplin JR, Granja I, et al. Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats. J Am Soc Nephrol. 2019;30(7):1163-1173.
Krieger, N. S., Asplin, J. R., Granja, I., Ramos, F. M., Flotteron, C., Chen, L., Wu, T. T., Grynpas, M. D., & Bushinsky, D. A. (2019). Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats. Journal of the American Society of Nephrology : JASN, 30(7), 1163-1173. https://doi.org/10.1681/ASN.2018101066
Krieger NS, et al. Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats. J Am Soc Nephrol. 2019;30(7):1163-1173. PubMed PMID: 31101664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats. AU - Krieger,Nancy S, AU - Asplin,John R, AU - Granja,Ignacio, AU - Ramos,Felix M, AU - Flotteron,Courtney, AU - Chen,Luojing, AU - Wu,Tong Tong, AU - Grynpas,Marc D, AU - Bushinsky,David A, Y1 - 2019/05/17/ PY - 2018/10/31/received PY - 2019/03/14/accepted PY - 2020/07/01/pmc-release PY - 2019/5/19/pubmed PY - 2020/4/21/medline PY - 2019/5/19/entrez KW - calcium KW - hypercalciuria KW - kidney stones SP - 1163 EP - 1173 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 30 IS - 7 N2 - BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality. SN - 1533-3450 UR - https://www.unboundmedicine.com/medline/citation/31101664/Chlorthalidone_Is_Superior_to_Potassium_Citrate_in_Reducing_Calcium_Phosphate_Stones_and_Increasing_Bone_Quality_in_Hypercalciuric_Stone_Forming_Rats_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=31101664 DB - PRIME DP - Unbound Medicine ER -