Some Progress in Therapy, But Still a Devastating Disease: Hepatorenal Syndrome

How can hepatorenal syndrome best be prevented in the primary care setting?

The combination of acute/subacute renal failure in the setting of cirrhosis can be caused by many factors, but one entity—hepatorenal syndrome (HRS)—is the most serious, with a prohibitive prognosis. Although it is considered a subspecialty disease—managed by gastroenterologists-hepatologists and nephrologists—it can be prevented, in some instances, through informed primary care. A recent “Top Paper” provides an important perspective.¹

HEPATORENAL SYNDROME: AN OVERVIEW

HRS is an accompaniment of severe cirrhosis leading to splanchnic arterial vasodilatation as a result of increased nitric oxide. The secondary vasodilatation stimulates the renin-angiotensin-aldosterone system as well as the sympathetic nervous system and vasopressin. The kidney is vasoconstricted by these events, so blood flow and glomerular filtration rate decline. Recent studies have also implicated a decrease in cardiac and adrenal function.¹

Modifications in the criteria for the diagnosis of HRS since 2007 are^1,2:

•Creatinine clearance is no longer used for diagnosis.

•An ongoing bacterial infection does not exclude HRS unless septic shock occurs.

•Albumin is preferred to normal saline for volume expansion.

•Low urine output and sodium level are no longer used for diagnosis of HRS.

What comprises therapy for HRS today? Terlipressin (not available in the United States), a synthetic vasopressin with greater effect on the V₁ receptor (vascular smooth muscle), plus albumin, transjugular intrahepatic portosystemic shunting (“TIPS”), and midodrine have all been used, especially in combinations. These (excepting albumin and antibiotics) require subspecialty assistance. Dialysis is usually reserved as a bridge for patients who are awaiting liver transplant.

SPECIFIC PRIMARY CARE INTERVENTIONS

Identify or avoid precipitants. A precipitating event can be identified in 70% to 100% of patients with HRS. Precipitants can be prevented or diagnosed early in primary care practice: a bacterial infection, a large volume paracentesis without albumin replacement, gastrointestinal bleeding, and acute alcoholic hepatitis.

Prevent spontaneous bacterial peritonitis. The bacterial infection can be spontaneous bacterial peritonitis (SBP). Primary care practitioners should use appropriate prophylaxis for selected patients to prevent SBP. When a paracentesis is performed, portal hypertension will be diagnosed as a result of cirrhosis (based on a serum-to-ascites albumin gradient of greater than 1.1). For prophylaxis to be instituted, infection should be absent and therefore there will be fewer than 250 white cells in the fluid. If the total protein in the ascitic fluid is low (1.5 grams or less), the patient is at high risk for SBP (and then HRS) and should receive either norfloxacin or trimethoprim/sulfamethoxazole as prophylaxis to prevent SBP.^3,4 In addition, beta-blockers, frequently used for prophylaxis against
variceal bleeding, also protect against SBP and HRS.⁵

Treat spontaneous bacterial peritonitis if it occurs. If SBP has already occurred, treatment with intravenous albumin (1.5 g/kg body weight followed by 1 g/kg 48 hours later) plus ceftriaxone has been demonstrated to reduce the incidence of HRS from 33% to 10%.¹

Although HRS is traditionally viewed as a subspecialty disease, primary care attention to selected details (timing of paracentesis, albumin replacement for large volume paracentesis, use of antibiotics and beta-blockers for prophylaxis) can prevent and attenuate HRS, and as a result decrease mortality.