Hepatorenal syndrome: Paving a pathway from a fatal condition to an opportunity to preserve kidney function

Abstract

In the 19^th century, von Frerichs F and Flint A identified a type of acute renal impairment associated with advanced liver disease, characterized by oliguria, absence of proteinuria, and normal renal histology, which was later termed hepatorenal syndrome (HRS). HRS primarily affects cirrhotic patients with ascites and often follows severe infections, digestive hemorrhages, or high-volume paracentesis. Pathophysiologically, HRS involves low glomerular filtration rate, hypotension, renin-angiotensin axis activation, water clearance, hyponatremia, and minimal urinary sodium excretion. These conditions mimic those seen in decreased effective circulatory volume (ECV) scenarios such as septic shock or heart failure. HRS represents a specific form of prerenal acute kidney injury (AKI) in patients with baseline renal ischemia, where the kidney attempts to correct decreased ECV by retaining sodium and water. Intense renal vasoconstriction, passive hyperemia from ascites, and acute tubular necrosis (ATN) with specific urinary sediment changes are observed. Persistent oliguria may transition HRS to ATN, although this shift is less straightforward than in other prerenal AKI contexts. Notably, liver grafts from HRS patients can recover function more rapidly than those from other ischemic conditions. Experimental studies, such as those by Duailibe et al, using omega-3 fatty acids in cirrhotic rat models, have shown promising results in reducing oxidative stress and improving kidney function. These findings suggest potential therapeutic strategies and underscore the need for further research to understand the mechanisms of HRS and explore possible treatments. Future research should address the impact of omega-3 on survival and secondary outcomes, as well as consider the balance of therapeutic risks and benefits in severe liver disease.

Keywords: Hepatorenal syndrome; Acute kidney injury; Oliguria; Ascites; Hibernation; Cirrhosis

Core Tip: Hepatorenal syndrome involves low glomerular filtration rate, hypotension, renin-angiotensin axis activation, decreased water clearance, hyponatremia, and minimal urinary sodium excretion, similar to prerenal acute kidney injury. Notably, liver grafts from these patients can recover function more rapidly than those from other ischemic conditions. Experimental findings suggest potential therapeutic strategies and underscore the need for further research to understand the mechanisms of hepatorenal syndrome and explore possible treatments.