EA Hwang, SB Park, HC Kim

Clinical experience with acetate-free dialysate

in chronic hemodialysis patients

Department of Internal Medicine, Keimyung University School of Medicine, Kidney Institute

Dialysis solutions are usually prepared from concentrates

and contain either acetate or bicarbonate as a buffer.

Recently, bicarbonate containing concentrates have been

introduced.

- more physiological

- better control of acidosis

- fewer complications and side-effects during dialysis

Drawback of Bicarbonate dialysis fluid;

solute precipitation

provide as a solid or liquid separately

include small amounts of acetic or lactic acid

with the calcium and magnesium

( lowers the pH of the final solution to 7-7.4,

ensures solubility of the salts)

Acetic Acid in Dialysis Fluid

Metabolized to acetyl coenzyme A

in peripheral tissues and the liver

capture a single hydrogen ion

release the hydrogen ion into

the respiratory tract by decarboxylation

Small amount: 2-8mEq/L in dialysis fluid

(Plasma conc of acetate <100umol/L)

Significant transfer of acetate to the patient

Patients are subjected to a certain amount

of acetate loading during standard HD

and on-line HDF.

Acetic Acid in Dialysis Fluid

Negative Effects of Acetate:

Noris M et al. AJKD 32:115-124, 1998Veech RL, Kidney Int 34:587-597, 1988

- Hypotension

- Myocardial depression

- Hypoxemia

- Abnomal lipid metabolism

- Oxydative stress

- Acid-base unbalance

- Glucidic intolerance

- Hyperphosphatemia

- Ectopic calcifications

No difference between pre-AD, pre-BD

and pre-AFB

AFB did not increase the stimulatory

effect of uremic plasma on endothelial

NO synthesis

Ahmad S. et al: AJKD 35:493, 2000

Advanced Renal TechnologiesFMC North America

920 Winter Street, Waltham, MA 02451 USA

Citrate as Acidifier in Dialysate

Physiologic anion (citric acid cycle)

Long history of use in medicine as anticoagulant

Dissolves easily, stable in solution

Citrate has ability to chelate calcium ions

Rapidly metabolized to bicarbonate (liver, muscle)

Citrate is not converted to acetyl-CoA

55% Heparin reduction using citrate dialysate

ASN’s 39th Annual Renal Week Meeting, Nov. 2006

Kossmann R.J., Callan R., Ahmad S.

2mo2mo

JASN 2009

Local anticoagulation effect of citrate

Prevents the blood cell activation

Significant increase in eKt/Vurea

Significant decline in predialysis conc

of Urea, Cr, PO4, β2-microglobulin

Citrate Dialysate Composition

(mEq/L)Artston® (KRD, Busan, Korea)

Composition Artston A2 Artston G1Na 140.0 140.0

K 2.0 2.0

Cl 114 114

Ca 2.5 2.5

Mg 1.0 1.0

HCO3 30.0 30.0

Citrate 2.0 2.0

Glucose (g/L) 0 1.0

Clinical application of Acetate – Free dialysate

(Artston A)

Preliminary study

6 patients

Safety

Feasibility

Total number of treatment 21Machine

Phoenix ® (Gambro) / Formula® (Bellco) 8 / 13Membrane

Polyflux 14L® (Gambro) / Diapes 512® (Bellco) 8 / 13Dialysate

Artston A2® (KRD) / Artston G1® (KRD) 20 / 1Anticoagulation

With heparin primingWithout heparin priming

(heparin-free)3

18Saline infusion

0123

21162

Dialysis treatment

Hemodynamic changes during treatment

Parameters ResultsHemoglobin (g/d) 8.9±0.6BUN (mg/dL) 47.9±10.3S. creatinine (mg/dL) 7.8±1.9Electrolyte Na+

(mEq/L) K+

Cl-

137.6±4.44.7±0.6

99.0±4.4

PO4 (mg/dL) 5.3±1.2

Mg (mg/dL) 2.5±0.4Total calcium (mg/dL) 8.7±0.6ionized calcium (mEq/L) 2.2±0.14Arterial pH

HCO3- (mmol/L)

7.39±0.0321.1±1.9

Laboratory findings

Parameters Pre dialysis post dialysis p

Total calcium 8.7±0.6 8.2±0.4 0.001

Ionized calcium 2.2±0.14 2.1±0.10 0.000

PT 13.3±1.5 12.0±2.5 0.014

aPTT 34.8±3.6 35.3±2.3 NS

Changes of coagulation factor

1. Residual coagulation in dialyzerGrade I < 5%Grade II < 25%Grade III < 50%Grade IV > 50%

2. Clotting in drip chamberGrade 1 no visible clotsGrade 2 mild clotsGrade 3 moderate clotsGrade 4 unable to continue HD

3. Hemostatic compression time( needle puncture site, end of dialysis)

Evaluation of clotting

Parameters No. of episode(n=21)

Percentage

Coagulation of dialyzer GIGIIGIIIGIV

13521

61.923.89.54.8

Clotting in venous chamber GIGIIGIIIGIV

41133

52.419.014.314.3

Hemostatic compression time(needle puncture site, end of dialysis )

17.8±11.8 min

Clotting of extracorporeal system

Adverse events No. of Episode(n=21)

Percentage

Intradialytic hypotensionwith symptomwithout symptom

03

014.3

Intradialytic hypertensionwith symptomwithout symptom

06

028.6

Headache 0 0Tingling sensation 0 0Itching sensation 0 0Muscle cramp 0 0Nausea /vomiting 0 0Chest pain 0 0

Adverse event during citrate dialysis

15 patients

Dose reduction of heparin

Prospective study

CHD AFHD CHD

0 4 weeks 16 weeks 20 weeks

Study Flow

Composition of dialysate

Na+ K+ Cl- Ca2+ Mg2+ HCO3- acetate Citrate Glucose

(g/L)

Artston® 140.0 2.0 114 2.5 1.0 30.0 - 2.0 0

Bicart® 140.0 2.0 109.5 3.5 1.0 34.0 3.0 - 0

(mEq/L)

Technical parameters

Parameters CHD AFHD

Dialyzer Polyflux 14L (1.4m2)/ Bellco BLS 512(1.2m2)

Dialysate Bicart® Artstone®

Qb 200-250ml/min

Qd 500ml/min

Heparin

Priming 2000 IU 2000 IU

Maintenance 600 IU/Hr None

Dose of heparin during hemodialysis

Dos

e of

hep

arin

/ses

sion

(IU

)

P<0.000

33.8% reduction

Body weight change and fluid removalB

ody

wei

ght (

kg)

Pre-treatmentPost-treatmentFluid removal

Comparison of Laboratory findings: CHD vs. AFHD

Parameters CHD AFHD p

Hb 10.0±0.9 9.7±1.9 ns

K+ 5.1±1.2 4.9±0.9 ns

HCO3- 21.5±3.2 20.7±3.1 ns

BUN 55.8±21.7 60.4±25.2 ns

S-Cr 10.7±3.3 10.4±3.1 ns

S-Alb 3.7±0.3 3.7±0.3 ns

t-Chol 151.7±28.9 144.8±36.2 ns

PO4 5.6±2.1 6.3±2.4 ns

iPTH 171.3±185.5 221.9±210.3 ns

Comparison of Laboratory findings: CHD vs. AFHD

Parameters CHD AFHD p

t-Calcium 8.7±0.5 8.6±0.6 ns

ionized calcium 2.3±0.2 2.3±0.2 ns

β2-M 24.8±5.9 28.3±8.9 ns

Myoglobulin 310.6±142.8 367.8±269.8 ns

Kt/Vurea 1.1±0.3 1.2±0.3 ns

URR 59.8±8.2 61.2±8.3 ns

Acetate-free dialysate is safe and can be used

without associated technical and clinical problems

Use of acetate-free dialysate permitted a 33.8%

reduction in the dose of heparin during hemodialysis

Acetate free dialysate can be used safely in a

chronic dialysis setting without clinical problems and

also the use of citrate instead of acetate in

bicarbonate dialysate can reduce dosage of

heparin used during hemodialysis treatment. In the

future, long-term, prospective studies are needed to

assess clinical outcome of this new dialysate.

Thank you for your attention