Sodium thiosulfate prevents vascular calcifications in uremic rats.
Accelerated vascular calcification is a severe complication of chronic kidney disease contributing to high morbidity and mortality in patients undergoing renal replacement therapy. Sodium thiosulfate is increasingly used for the treatment of soft tissue calcifications in calciphylaxis. Therefore, we determined whether it also prevents development of vascular calcifications in chronic kidney disease. We found that uremic rats treated by thiosulfate had no histological evidence of calcification in the aortic wall whereas almost three-fourths of untreated uremic rats showed aortic calcification. Urinary calcium excretion was elevated and the calcium content of aortic, heart, and renal tissue was significantly reduced in the thiosulfate-treated compared to non-treated animals. Sodium thiosulfate treatment transiently lowered plasma ionized calcium and induced metabolic acidosis. It also lowered bone strength in the treated animals compared to their normal controls. Hence, sodium thiosulfate prevented vascular calcifications in uremic rats, likely by enhancing acid- and/or chelation-induced urinary calcium loss. The negative impact on rat bone integrity necessitates a careful risk-benefit analysis before sodium thiosulfate can be used in individual human patients.
Pasch
Andreas
A
Department of Nephrology and Hypertension, Inselspital, University of Bern, Bern, Switzerland.
Schaffner
Thomas
T
Huynh-Do
Uyen
U
Frey
Brigitte M
BM
Frey
Felix J
FJ
Farese
Stefan
S
D000818:Animals; D001018:Aortic Diseases; D001842:Bone and Bones / Q000187:drug effects; D002114:Calcinosis / Q000188:drug therapy*; D002118:Calcium / Q000032:analysis / Q000652:urine; D007674:Kidney Diseases / Q000150:complications*; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013885:Thiosulfates / Q000494:pharmacology*; D014511:Uremia; D014652:Vascular Diseases / Q000188:drug therapy
D013885:Thiosulfates; C017717:sodium thiosulfate; D002118:Calcium