Pathophysiology of Hepatorenal Syndrome – Acute Kidney Injury

Hepatorenal syndrome is a complication of liver cirrhosis with ascites that results from the complex interplay of many pathogenetic mechanisms. Advanced cirrhosis is characterized by the development of hemodynamic changes of splanchnic and systemic arterial vasodilatation, with paradoxical renal vasoconstriction and renal hypoperfusion. Cirrhosis is also an inflammatory state. The inflammatory cascade is initiated by a portal hypertension-induced increased translocation of bacteria, bacterial products, and endotoxins from the gut to the splanchnic and then to the systemic circulation. The inflammation, whether sterile or related to infection, is responsible for renal microcirculatory dysfunction, microthrombi formation, renal tubular oxidative stress, and tubular damage. Of course, many of the bacterial products also have vasodilatory properties, potentially exaggerating the state of vasodilatation and worsening the hemodynamic instability in these patients. The presence of cardiac dysfunction, related to cirrhotic cardiomyopathy, with its associated systolic incompetence, can aggravate the mismatch between the circulatory capacitance and the circulation volume, worsening the extent of the effective arterial underfilling, with lower renal perfusion pressure, contributing to renal hypoperfusion and increasing the risk for development of acute kidney injury. The presence of tense ascites can exert an intra-abdominal compartmental syndrome effect on the renal circulation, causing renal congestion and hampering glomerular filtration. Other contributing factors to renal dysfunction include the tubular damaging effects of cholestasis and adrenal dysfunction. Future developments include the use of metabolomics to identify metabolic pathways that can lead to the development of renal dysfunction, with the potential of identifying biomarkers for early diagnosis of renal dysfunction and the development of treatment strategies.