title: Characterization of treatment dose delivered by albumin dialysis in the treatment of acute renal failure associated with severe hepatic dysfunction.
abstract: BACKGROUND
  Acute liver cell failure (ALCF) commonly results in death and when complicated by acute renal failure (ARF), the mortality approaches 90%. Albumin dialysis allows partial replacement of some of the liver's excretory functions. The molecular absorbents recirculating system (MARS) has been recently introduced to provide this therapy. Thus allowing bridging to transplantation or hepatic regeneration. We have attempted to define the degree of "uremic" dialysis that this system can deliver as well as characterizing the dose of "hepatic" treatment, using a similar approach to solute remove as applied to assessing hemodialysis adequacy. As a secondary issue we also report on the clinical outcomes of this group of patients.
  
  
  METHODS
  We treated 7 patients with ALCF and acute renal failure (6 of the patients having a formal diagnosis of hepatorenal syndrome), aiming to deliver a 5 treatment consecutive course consisting of 8 hours of albumin dialysis using the MARS monitor, combined with hemodialysis. Clinical and biochemical outcomes were assessed, and dialysis adequacy measured using urea reduction ratios, calculated Kt/V and measured Kt/V (using ionic dialysance). Treatment dose, with respect to the highly protein bound and lipophilic toxins that accumulate in hepatic failure, was assessed by calculating the bilirubin reduction ratio and percentage reduction in plasma ammonia and total bile acids.
  
  
  RESULTS
  All of the patients had a degree of biochemical improvement with albumin dialysis. Urine output increased and the degree of encephalopathy improved. Mean bilirubin fell from 612 +/- 105.5 micromol/l (range 165.6 - 1,024 micromol/l) to 370.4 +/- 49.7 micromol/l (range 190.4 - 569.2 micromol/l), ALT reduced from 3,280 +/- 2,266 IU/l (range 40 - 18,876) to 639 +/- 230 IU/l (range 33 - 1677). Hepatic synthetic function improved with INR falling from 4.1 +/- 0.5 (range 2.1 - 6.4) to 2.8 +/- 0.6 (range 1.4 - 5.5). Plasma ammonia was reduced, falling from 162.4 +/- 15.4 (range 131.1 - 191.9 micromol/l) to 73.1 +/- 15 micromol/l (range 45.6 - 106.4 micromol/l). Bile acid levels fell from 132 +/- 10.2 micromol/l (range 110.7 - 155.8 micromol/l) to 36.9 +/- 6.1 micromol/l (range 24.6 49.6 micromol/l). The mean urea reduction ratio (URR) was 58.4 +/- 3.2% (range 39 - 76%). Mean Kt/V as assessed by ionic dialysance was 1.7 +/- 0.01 (range 0.8-2.4). Mean bilirubin reduction ratio (BRR) was 28.6 +/- 1.4% (range 12.5 - 39%). BRR was proportional to both URR and Kt/V. BRR was also proportional to the percentage reduction of ammonia and bile acid levels. Three of the 7 patients survived to be discharged from hospital and 4 died.
  
  
  CONCLUSIONS
  Albumin dialysis appears capable of improving the outcome in patients with ALCF and hepatorenal syndrome. Eight-hour intermittent treatments with the MARS system in combination with hemodialysis deliver an adequate dose of dialysis with respect to urea. BRR may be an appropriate tool to allow further quantitative and comparative study of this technique.
authors.affiliation: Department of Renal Medicine, Derby City General Hospital, UK. Chris-mcintyre@lineone.net
authors.forename: C W
authors.initials: CW
authors.lastname: McIntyre
authors.forename: R J
authors.initials: RJ
authors.lastname: Fluck
authors.forename: J G
authors.initials: JG
authors.lastname: Freeman
authors.forename: S H
authors.initials: SH
authors.lastname: Lambie
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D006435:Renal Dialysis / Q000295:instrumentation* / Q000379:methods*; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000418:Albumins