CIN '2007 - 4th CONGRESS OF NEPHROLOGY IN INTERNET
Urinary Excretion of Aquaporins in Cirrhosis. Relationship with Ascites and Hepatorenal Syndrome
Dr C. Esteva-Font P. Ginès, Dr P. Fernández-Llama
Fundació Puigvert and Hospital Clinic, Barcelona.-
Abstract
Liver cirrhosis is associated with the altered regulation of sodium and water metabolism Disordered regulation of sodium and water transport in the kidney is responsible for altered salt and water balance in several pathophysiological states, including cirrhosis. Water reabsorption from renal tubules requires not only a favorable solute concentration gradient but also pores for the water molecules to exit renal tubules via a family of proteins named aquaporins. Several aquaporins are expressed in the kidney . Aquaporin-2, recognized as the “vasopressin-regulated water channel” is expressed in the apical membrane of the collecting duct cells . Several studies using experimental models of cirrhosis have reported contrasting results regarding aquaporin-2 expression in the kidney. Asahina et al reported increases in aquaporin-2 following repetitive intraperitoneal injections of carbon tetrachloride . In contrast, we were unable to demonstrate an increase in aquaporin-2 protein abundance in rats with carbon tetrachloride-induced cirrhosis . However, these cirrhotic rats with ascites presented an increase of trafficking of aquaporin-2 to the plasma membrane and interestingly an increase in aquaporin-1 in the kidney. Studies of cirrhosis induced by common bile duct ligation have reported a decrease in aquaporin-2 expression in the kidneys of rats with ascites . These differences confirm that the physiological state reached in the two models is very different even though both are associated with salt and water retention. In humans, aquaporin proteins research has been done studying urinary aquaporin excretion due to the availability of the urine and the ethical conflict of obtaining kidney tissue. Excretion of aquaporin 2 in urine has been shown to correlate with vasopressin-stimulated water retention in experimental animal and human models of overhydration and water deprivation (5). Vasopressin has an immediate effect on aquaporin 2 concentrations within the apical membrane of collecting duct principal cells by stimulating its incorporation from a reservoir of cytoplasmic vesicles and a longer term effect by stimulating gene transcription. Given that 3%-4% of renal aquaporin is shed into the urine on a daily basis, increased vasopressin activity is reflected by an increase in urinary aquaporin 2 excretion in experimental animals and in human congestive cardiac failure. In this study, aquaporin-2 excretion was analyzed by immunoblotting in patients with liver cirrhosis during the progressive impairment of sodium and water metabolism in cirrhosis. Twenty-four hour urine was collected from healthy volunteers (n=11) and 13 patients with compensated cirrhosis (without ascites) and 20 patients with decompensated cirrhosis (11with ascites without renal failure and 9 with hepatorenal syndrome).Comments: