Effects of Citrate Acid Concentrate (Citrasate®) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial

Abstract

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.

Safe Use of Citric Acid-Based Dialysate and Heparin Removal in Postdilution Online Hemodiafiltration

“…In these studies, however, anticoagulation with heparin was maintained at the usual dose [6,8] or the dialyzer was reused [20]. Our results are similar to those obtained by Sands et al [11] comparing conventional hemodialysis treatments with a citrate dialysate and reduced doses of heparin. Ionic dialysance remained stable compared to a regular heparin dose and standard acetic acid based dialysate [11].…”

“…Studies evaluating the use of CitA-D in conventional hemodialysis usually found a decrease of total and ionized serum calcium during the sessions [6,11,19]. However, the dialysate calcium concentration was 1–1.25 mmol/l against 1.5 mmol/l in our study.…”

“…It allows better control of arterial hypertension by decreasing vascular resistances [9], an increase in predialytic bicarbonatemia, hemoglobinemia, and nutritional status [10]. In addition, the use of CitA-D could allow a decrease or even removal of heparin [4,11]. …”

Citrate Anticoagulation in Hemodialysis

“…Similar to calcium mass balance considerations, dialysis-related sodium loading is another topic that has been receiving more and more attention in recent years and is another domain of solute kinetic modeling that should ultimately be integrated into citrate dialysis modeling, particularly given the additional sodium load administered with the use of regional citrate anticoagulation. The use of dialysate-side citrate anticoagulation (i.e., the use of a citrate-and calciumcontaining dialysate without arterial citrate infusion or venous calcium substitution) has sparked interest recently for its alleged heparin-sparing potential and its safety and ease of use [27][28][29]. At unchanged heparin doses, using citrate-containing dialysate (instead of bicarbonate dialysate acidified with acetate) appears to improve solute removal [30].…”

Líquido dializante con citrato frente a acetato en pacientes en hemodiafiltración on-line de alta eficacia: parámetros a estudio

“…El empleo de líquido dializante con citrato puede incrementar la eficacia del dializador dado su conocido poder anticoagulante 6 , ya que actúa de forma temprana sobre el calcio en la cascada de la coagulación, así como disminuir la precipitación de sales cálcicas al actuar como quelante del calcio iónico. Además de estos beneficios, consigue una mejoría del equilibrio ácido-base dado su efecto tampón y una mayor tolerancia a la sesión de diá-lisis consecuencia de una mayor estabilidad cardiovascular 7 …”