High citrate dialysate and uses thereof

Abstract

The dose of dialysis in terms of urea clearance is marginal in many hemodialysis patients, and metabolic acidosis as determined by the pre-dialysis serum HCO 3 level is common. A dialysate that included citric acid rather than acetic acid as acidifying agent provides superior performance properties. Citrate-containing dialysate was used exclusively in 22 hemodialysis patients. Initially, only 8 of the 22 patients had a pre-dialysis serum HCO 3 >23 mEq/L (lower limit of normal), however, after 12 weeks of dialysis using the citrate-containing dialysate, the serum HCO 3 normalized in 15 patients (p=0.0001, Chi-square). Dialysis variables were kept constant in 19 of the patients, who also used and reused the same dialyzer model throughout. In these patients, the initial average urea reduction ratio (URR) was 68.5±5.9%, and after treatment with the citrate dialysate disclosed herein, this ratio had increased to 73±5.3% (p<0.03). SpKt/V, calculated using the Daugirdas II formula, also increased from 1.23±0.19 to 1.34±0.2 (p=0.01). This increased urea clearance may be the result of the anticoagulant property of citrate maintaining patency of the dialyzer membrane. The increase in pre-dialysis serum HCO 3 may represent increased delivery from the dialysate and production from citric acid.

1 - 31 . (canceled) 
     
     
         32 . A method of performing dialysis on a patient in need thereof, wherein the method comprises:
 a) performing the dialysis wherein the patient is heparin-free during the time of dialysis; and   b) performing the dialysis in a dialyzer with a dialysate composition comprising citrate at a concentration ranging from 2.4 to 20 mEq/L, calcium at a concentration ranging from 2.5 to 5 mEq/L and magnesium at a concentration ranging from 0.75 to 2 mEq/L, wherein the patient has an intolerance to heparin, an antibody to heparin, a risk of bleeding from the use of direct administration of heparin or chronic acidosis.   
     
     
         33 . The method of  claim 32  wherein the dialysis results in an increased urea transfer from the patient's blood to the dialysate in comparison to the level of urea transfer obtained with dialysate compositions that do not contain citrate. 
     
     
         34 . The method of  claim 32  wherein the dialysis results in an increased level of bicarbonate concentration in the patient's blood in comparison to the level of bicarbonate concentration obtained with dialysate compositions that do not contain citrate. 
     
     
         35 . The method of  claim 32  wherein the dialysis results in an increased effective flow of the patient's blood through the dialyzer in comparison to the effective rate of blood flow obtained with dialysate compositions that do not contain citrate. 
     
     
         36 . The method of  claim 32  wherein the dialysis results in an increased re-use of the dialyzer in comparison to the re-use of a dialyzer obtained with dialysate compositions that do not contain citrate. 
     
     
         37 . The method of any one of  claims 32  to  36  wherein the dialysate composition comprises citrate at a concentration ranging from 3.0 to 10 mEq/L. 
     
     
         38 . The method of  claim 37  wherein the citrate is in the form of citric acid, sodium dihydrogen citrate, disodium hydrogen citrate, trisodium citrate, potassium dihydrogen citrate or dipotassium hydrogen citrate, or any mixture thereof.