Hepatorenal syndrome: emerging perspectives of pathophysiology and therapy

Progressive oliguric renal failure (designated "hepatorenal syndrome") commonly complicates the course of patients with advanced hepatic disease. Despite the severe derangement of renal function and ominous prognosis when renal failure develops, minimal and inconsistent pathologic abnormalities of the kidneys are found at autopsy. Furthermore, the kidneys, if transplanted, are capable of normal function, which supports the concept that the renal failure is functional and potentially reversible. In contrast to patients with classical acute failure (ATN), hepatorenal syndrome patients manifest characteristic alterations of renal function including (1) relatively hyperosmolar urine; (2) high creatinine urine:plasma ratio, and (3) a very low urine sodium concentration (< 10 mEq/L). The past several years have witnessed newer insights into both the pathophysiology and the therapeutics of this syndrome. The application of newer methodology such as tracer kinetics has more rigorously delineated the role of a number of pathogenic mechanisms including activation of the sympathetic nervous system. The characterization of endothelin and the nitric oxide-arginine pathway and their roles in biology and medicine has provided additional new insights with regard to the pathogenesis of hepatorenal syndrome. For example, nitric oxide has been proposed to constitute a mediator of both the hyperdynamic circulation and renal failure. Finally, recently initiated therapeutic approaches lend a note of optimism to the future management of a syndrome that is so often incompatible with recovery. These include the acceptance of orthotopic liver transplantation as definitive treatment for patients with end-stage liver disease and attempts to improve renal function by countervailing the decreases in systemic vascular resistance while minimizing concomitant increments in renal vascular resistance. Hopefully, ongoing and future clinical trials will establish the precise contribution of each of these treatment modalities and their respective roles in the therapeutic armamentarium.