Intradialytic use of sodium thiosulfate
Provided herein are methods for maintaining physiological levels of thiosulfate in a subject undergoing hemodialysis. Also provided herein are methods of administering pharmaceutically acceptable sodium thiosulfate to a subject undergoing hemodialysis.
1. A method for maintaining physiological levels of thiosulfate in a subject undergoing hemodialysis; preventing myocardial infarction in a subject undergoing dialysis; preventing sudden cardiac death in a subject undergoing dialysis; preventing stroke in a subject undergoing dialysis; preventing cardiovascular disease that is characterized by tissue ischemia in a subject undergoing dialysis; preventing high blood pressure in a subject undergoing dialysis; preventing pulmonary hypertension in a subject undergoing dialysis; preventing renal hypertension in a subject undergoing dialysis; or preventing atherosclerosis in a subject undergoing dialysis, comprising intradialytically contacting said subject's blood with a dialyzer membrane that is also in contact with a thiosulfate-spiked dialysate, wherein an aqueous solution comprising sodium thiosulfate is added to an unspiked dialysate as the unspiked dialysate flows from a dialysis machine to a dialyzer membrane, wherein said unspiked dialysate comprises a mixture of water, an acid concentrate solution, and a bicarbonate concentrate solution, and wherein said thiosulfate-spiked dialysate has a pH greater than about 7.0, and wherein the concentration of thiosulfate in said thiosulfate-spiked dialysate is no more than about 10 micromolar.
2. The method of claim 1 , wherein the physiological level of thiosulfate in said subject is no more than about 10 micromolar.
3. The method of claim 1 , wherein the physiological level of thiosulfate in said subject is between about 500 nanomolar and about 5 micromolar.
4. The method of claim 1 , wherein the physiological level of thiosulfate in said subject is about 3 micromolar.
5. The method of claim 1 , wherein the concentration of thiosulfate in said thiosulfate-spiked dialysate is between about 500 nanomolar and about 5 micromolar.
6. The method of claim 1 , wherein the concentration of thiosulfate in said thiosulfate-spiked dialysate is about 3 micromolar.
7. The method of claim 1 , wherein said aqueous solution comprising sodium thiosulfate comprises no more than about 300 mg/L of sodium thiosulfate.
8. The method of claim 1 , wherein said water comprises no more than about 200 mg/L of thiosulfate.
9. The method of claim 1 , wherein said aqueous solution comprising sodium thiosulfate is added to said unspiked dialysate through a valve that is attached to dialysate tubing at a location before said tubing connects to the dialyzer.
10. The method of claim 9 , wherein said unspiked dialysate flows through said dialysis tubing at a rate between about 500 mL/min and about 700 mL/min.
11. The method of claim 9 , wherein said unspiked dialysate flows through said dialysis tubing at a rate of about 600 mL/min.
12. The method of claim 9 , wherein said aqueous solution comprising sodium thiosulfate is added through said valve to said unspiked dialysate at a rate between about 100 mL/hr and about 550 mL/hr.
13. The method of claim 9 , wherein said aqueous solution comprising sodium thiosulfate is added through said valve to said unspiked dialysate at a rate of about 250 mL per hour.
14. The method of claim 1 , wherein the pH of said thiosulfate-spiked dialysate is between about 7.3 and about 7.5.
15. The method of claim 1 , wherein the pH of said thiosulfate-spiked dialysate is about 7.4.
16. The method of claim 1 , wherein said subject is a human with chronic renal failure.
17. The method of claim 1 , wherein said subject is a human with acute renal failure.
18. The method of claim 1 , wherein said subject undergoes dialysis from three to seven times per week.