Hepatorenal Syndrome

Abstract

Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver-kidney transplantation.

Keywords: Albumins; Biomarkers; Early Diagnosis; Hepatorenal Syndrome; Inflammation; Kidney Tubular Necrosis, Acute; Liver Cirrhosis; Liver Transplantation; Lypressin; Prognosis; Renal Circulation; Vasoconstriction; Vasoconstrictor Agents; acute kidney injury; glomerular filtration rate; hepatorenal; kidney transplantation; liver transplantation; terlipressin.

Figure 1.

Mechanisms involved in AKI in decompensated cirrhosis. (A) In decompensated cirrhosis, both vasodilation secondary to portal hypertension and systemic inflammation induced by gut bacterial translocation tend to induce kidney arterial vasoconstriction because of the activation of vasoconstrictive systems in response to decreased effective blood volume and inflammation in the kidney inducing microvascular changes. These changes result in a hyperdynamic state characterized by increased cardiac output, ascites, and normal GFR, but increase susceptibility of the kidney to AKI. (B) The onset of hepatorenal syndrome corresponds to the most advanced stages of these changes, with an intense kidney vasoconstriction and impaired kidney autoregulation leading to a decrease in GFR. Any event further decreasing hypovolemia (bleeding, diuretics overdose, lactulose-induced diarrhea), decreased cardiac output (e.g., cirrhotic cardiomyopathy, nonselective β-blockers) or systemic inflammation, with or without over sepsis, can precipitate hepatorenal syndrome. AVP, arginine vasopressin; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system.

Figure 2.

Algorithm for workup and management of AKI. *A trial of octreotide/midodrine (maximum 3 days) can be attempted before initiation of norepinephrine. ACS, abdominal compartment syndrome; AIN, acute interstitial nephritis; ATN, acute tubular necrosis; BPH, benign prostatic hypertrophy.