The efficacy and safety profile of albumin administration for patients with cirrhosis at high risk of hepatorenal syndrome is dose dependent

Abstract

Background: Albumin is a critical component in the standard therapeutic approach to acute renal failure (ARF) and spontaneous bacterial peritonitis (SBP) in the setting of ascites. However, data regarding the safety and minimum effective dose are limited.Methods: We conducted a retrospective review of patients with decompensated cirrhosis who received albumin within the first 48 hours of hospitalization at Beth Israel Deaconess Medical Center between 2010 and 2013. Outcomes included 90-day risk of death or transplantation (primary) and (secondary) complications of albumin infusion (length of stay (LOS) and need for critical care)), all adjusted for comorbidity and severity of illness.Results: We included 169 patients with ARF and 88 patients with SBP. The optimal doses of albumin for a survival benefit were found to be 87.5 g and 100 g in the ARF and SBP cohorts, respectively. The odds ratio (OR) for the 90-day risk of death or liver transplantation associated with the optimal loading dose was 0.36 (95% CI: 0.17–0.76, P = 0.008) and 0.28 (95% CI: 0.07–0.97, P = 0.04) for the ARF and SBP cohorts, respectively. This effect persisted for patients with ARF who had neither hepatorenal syndrome (HRS) nor SBP (OR: 0.13, 95% CI: 0.007–0.79, P = 0.02). LOS (beta coefficient per log albumin dose: 1.69; 95% CI: 0.14–3.24, P = 0.03) and risk of critical care (OR/g albumin: 1.03; 95% CI: 1.01–1.05, P = 0.01) were also dose dependent.Conclusion: Albumin has a dose-dependent effect on both survival and complications in patients with cirrhosis with ARF (HRS and otherwise) and/or SBP.

Fluid balance concepts in medicine: Principles and practice

“…Infusion of albumin plus norepinephrine may be beneficial in HRS 1[ 255 ]. Albumin has dose-dependent effects in both increasing survival and reducing complications in cirrhotic patients with HRS[ 261 ]. The beneficial effects of albumin infusion are not due solely to its oncotic properties.…”

Acute Kidney Injury in Cirrhosis

“…In stages 2 and 3, the patients who meet diagnostic criteria of HRS-AKI should be treated with vasoconstrictors in combination with albumin [35]. The albumin initial dose is 1 g/kg body weight up to 100 g on the first day, then ongoing with 20-40 g/day, as it has been shown that the effects of intravenous albumin in the prevention and treatment of HRS are dosedependent, with better results when higher cumulative doses were administered [51,52]. In all large-volume paracentesis (>5 L, with 8 g/L of ascites removed), albumin should be administered since it prevents post-paracentesis circulatory dysfunction, which reduces the risk of renal dysfunction and improve survival [53,54].…”

Perioperative Risk Assessment and Management of Cirrhotic Patients

“…During surgery, hemorrhage and anesthetic effects may precipitate a reversible HRS [32]. HRS-1/2 should be referred for LT, and managed with albumin 1 g/kg/d increasing to 100 g loading dose followed by 20-40 g/d [72] combined with vasconstrictor treatment [65,73]. Although not available in the U.S., terlipressin plus albumin maintains better MAP [72] with a higher rate of renal recovery at 70% compared to midodrine and octreotide plus albumin in the treatment of HRS at 28.6% [74], despite higher rates of cardiovascular side effects [75].…”

“…Decompressive TIPS → ↑ Surgery candidacy [73,[96][97][98][99][100] Maintain Albumin ≥2.5 [78,102] Albumin 1 g/kg/d for 2 d trial [72] Unaffected by PPI administration [95] Endocrine Adrenal Failure [59][60][61][62] Impaired liver synthesis of APO-A1 → ↓ HDL → ↓ cholesterol precursor → impaired cortisol synthesis ↑ TNF-α, IL-1β, IL-6, and endotoxin → ↓ synthesis/release of apoA-1, ↑ tissue cortisol resistance Potential use for supplementary hydrocortisone and fludricortisone treatment during sepsis/septic shock [165] Renal Hepatorenal Syndrome [69] HRS type 1: Doubling of Cr (above 2.5 mg/dL) and ↓ CrCl by 50% (or >20 mL/min) in less than 2 weeks 1 month mortality exceeds 50%.…”

“…HRS Mechanism: [64][65][66][67][68][69] PHTN → splanchnic arterial vasodilation → ↑ portal venous flow/PHTN Sodium retention with water and ascites develop → ↑ endogenous natriuretic hormones ↑ sodium retention → ↑ plasma renin activity and NE levels Extra-splanchnic organ vasoconstriction compensates splanchnic arterial vasodilation → ↓renal/cerebral/muscular flow ↑ plasma renin and NE, ↓ renal perfusion and GFR → ↑ADH and ↓ free water clearance HRS Prevention: [48,72,166] During 48,70,71,74] Avoid excess fluid administration…”