A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease.
BACKGROUND
We prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with end-stage renal disease (ESRD) during hemodialysis.


METHODS
In this randomized, 3-way crossover study, ESRD patients underwent hemodialysis sessions of 3- or 4-hour duration using high-flux membranes and each of 3 argatroban treatment regimens (A: 250-microg/kg bolus, with an additional 250-microg/kg bolus allowed; B: 250-microg/kg bolus followed by 2-microg/kg/min infusion; C: steady-state, 2-microg/kg/min infusion initiated 4 hours before dialysis). Pharmacodynamic effects including activated clotting times (ACTs); hemodialysis efficacy including single-pool Kt/V, urea reduction ratio (URR), and circuit flow; and safety through a 3-day follow-up were monitored. Argatroban pharmacokinetic parameters including dialytic clearance were evaluated during regimen C.


RESULTS
Thirteen patients completed 38 hemodialysis sessions (1 patient withdrew consent after 2 sessions). Mean +/- SD ACTs increased from 131 +/- 14 seconds at baseline to 153 +/- 24, 200 +/- 30, and 197 +/- 33 seconds, respectively, after 60 minutes of hemodialysis using regimens A, B, and C. Across regimens, mean Kt/Vs (1.5-1.6) and URRs (70%-73%) were comparable. No dialyzer was changed; 1 session was shortened 15 minutes because of circuit clot formation. Systemic argatroban clearance increased approximately 20% during hemodialysis, without clinically significantly affecting ACTs. Upon argatroban discontinuation, ACTs and plasma argatroban decreased concurrently (elimination half-life, 35 +/- 6 min). No thrombosis, bleeding, serious adverse events, or clinically significant changes in vital signs or routine laboratory measures occurred.


CONCLUSIONS
Argatroban, administered by each treatment regimen, provides safe, adequate anticoagulation to enable successful hemodialysis in ESRD patients. Argatroban dialytic clearance by high-flux membranes is clinically insignificant.
Murray
Patrick T
PT
Nephrology Section, University of Chicago, Chicago, Illinois 60657, USA. pmurray@medicine.bsd.uchicago.edu
Reddy
Bharathi V
BV
Grossman
Eric J
EJ
Hammes
Mary S
MS
Trevino
Sharon
S
Ferrell
Janice
J
Tang
Ignatius
I
Hursting
Marcie J
MJ
Shamp
Trisha R
TR
Swan
Suzanne K
SK
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001120:Arginine / Q000031:analogs & derivatives; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods* / Q000592:standards; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban