Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.
calcium oxalate
chlorthalidone
hypercalciuria
nephrolithiasis
potassium citrate
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
01
06
2020
revised:
16
12
2020
accepted:
17
12
2020
pubmed:
9
1
2021
medline:
22
6
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.
Identifiants
pubmed: 33417997
pii: S0085-2538(20)31548-9
doi: 10.1016/j.kint.2020.12.023
pmc: PMC8076055
mid: NIHMS1660065
pii:
doi:
Substances chimiques
Calcium Oxalate
2612HC57YE
Potassium Citrate
EE90ONI6FF
Chlorthalidone
Q0MQD1073Q
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1118-1126Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK075462
Pays : United States
Informations de copyright
Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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