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The patient is a 69-year old woman from El Salvador with a chief complaint of worsening abdominal distension for nine months. Three months earlier, the patient was told she had liver problems and was started on diuretics. Prior to presentation, the patient states that she stopped taking her medication and noticed increasing lower extremity edema and abdominal girth, as well as an unintentional 15-pound weight loss. The patient denied any other medical problems, including fever, chills, or toxic habits. On presentation, the patient was afebrile, HR 60/min, BP 90/60 mmHg, RR 20/min, O2 sat 98% on room air. Physical exam was notable for decreased breath sounds at bases, shifting dullness, presence of fluid wave, palmar erythema and 2+ pitting lower extremity edema bilaterally. Laboratory data were notable for sodium of 128 mEq/L, potassium of 5.5 mEq/L, BUN of 60 mg/dl, creatinine of 5.5 mg/dl, platelets of 205K. Urinalysis was unremarkable; there was no evidence of proteinuria or pyuria, and the sediment was bland. Fractional excretion of sodium was calculated to be less than 0.7%. A renal consult was obtained, and the patient was started on albumin, leading to an improvement in her renal function. She underwent therapeutic paracentesis and diuresis, but several days into her hospitalization she developed worsening renal function.
Hepatorenal syndrome (HRS) is a diagnosis of exclusion. The major criteria include liver disease with advanced hepatic failure evidenced by portal hypertension, decreased GFR evidenced by Cr> 1.5 mg/dl or creatinine clearance <40 mL/min, absence of shock, bacterial infection, treatment with nephrotoxic drugs, or GI or renal fluid losses. Obstructive uropathy or parenchymal disease as visualized by ultrasound should be ruled out(1). It also is defined by lack of improvement in renal function following diuretic withdrawal and expansion of plasma volume with isotonic saline. Proteinuria <500 mg/dl is characteristic. There are two types of HRS. Type 1 is characterized by a rapid deterioration with a creatinine greater than 2.5 mg/dl over a two week period. Type II is characterized as a slower, more chronic progression of renal failure.
Albumin has some benefit in patients with spontaneous bacterial peritonitis(2). A study published in the New England Journal focused on prevention of renal failure and improvement in in-hospital mortality in cirrhotic patients diagnosed with spontaneous bacterial peritonitis (ascitic cell count of greater than 250 polymorphonuclear cells/cc without evidence of secondary peritonitis). One hundred twenty-six patients were blinded and randomized to receive cefotaxime with albumin versus antibiotics alone. After three months, 33% patients who received cefotaxime developed renal impairment versus 10% in the cefotaxime plus albumin group, p= 0.0002. There was decreased in-hospital mortality in patients who received albumin and antibiotics: 6 of 63 (10%) versus 18 of 63 (29%) in the group that received antibiotics alone (p=0.01).
There is limited literature in the use of albumin with regards to improvement in hepatorenal syndrome. One prospective study published in Gastroenterology studied 20 consecutive patients with hepatorenal syndrome. Varying amounts of albumin were given to maintain a CVP above 3 cm H20(3). Furosemide was given to support urine output. Eleven out of the 20 patients had shown statistically significant, if minimal, improvement in creatinine clearance:from 27 ± 7.0 mL/min to 30.4 ± 5.2 mL/min. There was benefit seen in the number of days of survival in the patients who responded to the albumin versus those who did not: 259 ± 113 days versus 14 ± 3 days, p < 0.0005. A limitation to this prospective study was its small sample size, but the significant increase in days of survival warrants larger studies to confirm this finding.
A recent study published in Gastroenterology (4) focused on improvement of renal function or survival in cirrhotic patients with hepatorenal syndrome treated with terlipressin, a vasopressin analog thought to improve renal perfusion by countering splanchnic vasodilation and increasing effective arteriolar volume. Forty-four patients were blinded and randomized to either receive terlipressin and albumin versus albumin alone for 15 days with follow-up at three months. Patients had similar baseline characteristics and after three months, improvement in renal function (reduction in serum creatinine below 1.5mg/dl or reduction in initial values by 50 percent) was seen in 10 of 23 patients (43.5%) who received both terlipressin and albumin versus 2 of 23 (8.7%) who only received albumin. There was no significant difference in survival at three months: 27% in the terlipressin and albumin group versus 19% in the albumin group. Small sample size and lack of double-blinding make this study less valid, but significant improvements in serum creatinine concentration suggest treatment consideration in this patient population.
There have been small studies evaluating possible benefit of transjugular intrahepatic portosystemic shunt (TIPS) in patients with hepatorenal syndrome, with the thought that decreasing portal pressures will improve subsequent renal failure. Thirty-one cirrhotic patients not deemed candidates for transplant who developed HRS received TIPS and were followed retrospectively for renal function and survival. There was an improvement in creatinine clearance from 18 to 48 ml/min and improvement in three-month survival to 81% when compared to similar patients who did not receive TIPS (10%). This study suggested that TIPS should be considered as an earlier intervention as several patients were taken off dialysis soon after the procedure.
Ultimately the treatment for HRS is liver transplantation, as it is the only modality to improve renal function. Factors such as patient demographics, limited organ donation, and coexisting comorbidities hinder this intervention from improving survival. Given lack of major trials in this particular field, prevention of progressive liver disease remains the ideal intervention.
1. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996;23:164–176.
2. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-409.
3. Peron JM, Bureau C, Gonzalez L, et al. Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study. Am J Gastroenterol 2005;100(12):2702-7.
4. Martin-Llahi, M, Pepin, MN, Guevara, M, et al. Terlipressin and albumin versus albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008;134:1352-1359.
5. Brensing KA, Textor J, Perz J, et al. Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: A phase II study. Gut 2000;47: 288–95
Reviewed by David Goldfarb, MD, Professor of Medicine, NYU Medical Center, Chief Nephrology Section VA New York Harbor