Improvement of hepatorenal syndrome with extracorporeal albumin dialysis mars: Results of a prospective, randomized, controlled clinical trial

Abstract

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

“…This method of removing albumin-binding toxins and water-soluble substances was found to result in decreases in hepatic encephalopathy, in increases in mean arterial pressure, and in improvements in kidney and liver function. 101,102) Acute liver failure may be the first manifestation of Wilson disease, in which copper metabolism is impaired. Liver transplantation is usually the preferred treatment if copper continues to accumulate in the patient's body.…”

Advances in Extracorporeal Detoxification by MARS Dialysis in Patients with Liver Failure

“…In the first prospective, randomized, controlled clinical trial, 13 patients with cirrhosis and hepatorenal syndrome type I were randomized to standard medical therapy or MARS treatment. A significant decrease in bilirubin and creatinine levels, together with a prolonged survival rate, was observed in the MARS group [30]. Moreover, in a series of 5 patients receiving a single MARS treatment an improvement of systemic vascular resistance and arterial pressure with a decrease in plasma renin activity was demonstrated [40].…”

“…There are some evidences that MARS device may decrease plasma levels of NO and other vasoactive molecules, that are responsible for the vasodilatation and hyperdinamic status of patients with liver failure [30].…”

Molecular adsorbent recirculating system is ineffective in the management of type 1 hepatorenal syndrome in patients with cirrhosis with ascites who have failed vasoconstrictor treatment

“…Details of MARS dialysis can be found in Mitzner et al 22. In short, patient's blood was passed through a non-albumin-permeable high flux dialysis membrane (Gambro, St Leonard Quebec, Canada) and filtered by a closed loop dialysate circuit containing 25% albumin pumped by a MARS machine (Gambro, St Leonard Quebec, Canada).…”

“…The recent development of molecular adsorbent recirculating system (MARS) dialysis, which enables the selective removal of water-soluble and albumin-bound substances20 21 of molecular weight <50 kDa, by transferring from albumin binding in the plasma to albumin binding in the dialysate, has made it possible to remove some of these albumin-bound vasodilators, thereby reducing the extent of systemic arterial vasodilatation. In a randomised controlled trial of MARS dialysis versus conventional haemodialysis and standard medical treatment in 13 patients with cirrhosis with type 1 HRS, patients who received MARS dialysis had a significant reduction in serum bilirubin (from 26.8±11.6 to 17.3±7.5 mg/dl) and serum creatinine (from 3.8±1.6 to 2.3±1.5 mg/dl), associated with an improved survival to 40% at 2 weeks 22. In another randomised controlled trial, 24 patients with cirrhosis with superimposed acute liver injury and progressive hyperbilirubinaemia had a reduction in bile acids (average <43%) and bilirubin (average <29%) with MARS treatment, together with improvement in hepatic encephalopathy, renal function and 30-day survival 23.…”