Immunologic, hemodynamic, and adrenal incompetence in cirrhosis: impact on renal dysfunction

Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and is associated with significant morbidity and mortality. Liver fibrosis and liver insufficiency, portal hypertension, systemic vasodilation, and a subsequent hyperdynamic circulation undermine the renal and cardiac function, making cirrhotic patients more susceptible to hemodynamic incidents. In addition, the immune system is impaired in cirrhosis, leading to an exaggerated production of vasoactive mediators, and the adrenal cortisol response is insufficient, which causes further impairment of the vascular tonus, cardiac output, and renal perfusion. Consequently, the cardiovascular and renal dysfunction is aggravated, resulting in a hepatorenal syndrome (HRS). HRS is seen exclusively in patients with liver disease and has been considered an entirely functional prerenal dysfunction, rather than a structural dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New research explores several new markers of renal dysfunction that may replace serum creatinine in the future and give new insight on the hepatic nephropathy. Our understanding of the pathophysiological mechanisms causing the immunologic, adrenal, and hemodynamic incompetence, and the impact on renal dysfunction, has improved in recent years, and in this review we aim to highlight recent achievements in this field.