Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome

Abstract

Several experimental models of cirrhosis have shown dysregulation of renal aquaporins in different phases of liver disease. We investigated the urinary excretion of both aquaporin-1 and aquaporin-2 in patients with cirrhosis at different stages of the disease. Twenty-fourhour urine was collected from 11 healthy volunteers, 13 patients with compensated cirrhosis (without ascites), and 20 patients with decompensated cirrhosis (11 with ascites without renal failure and 9 with hepatorenal syndrome). Aquaporin-1 and aquaporin-2 excretion was analyzed by immunoblotting. Urinary aquaporin-2 excretion was reduced in patients with cirrhosis compared to healthy subjects. A progressive decrease in urinary aquaporin-2 excretion was observed as the severity of cirrhosis increased, from compensated cirrhosis to cirrhosis with ascites and hepatorenal syndrome. Patients with hyponatremia had lower urinary aquaporin-2 excretion than patients without hyponatremia. Vasopressin plasma level did not correlate with aquaporin-2 excretion. There were no differences between healthy subjects and patients with cirrhosis with or without ascites in urinary excretion of aquaporin-1, but urinary aquaporin-1 excretion of those with hepatorenal syndrome was extremely low. In conclusion, patients with cirrhosis appear to exhibit a decreased abundance of renal aquaporin-2 and therefore lower water permeability in the collecting tubules. This may represent an adaptive renal response to sodium retention, with expansion of extracellular fluid volume and dilutional hyponatremia observed in those who have cirrhosis with ascites. Finally, aquaporin-1 does not appear to play a role in the progressive dysregulation of extracellular fluid volume in cirrhosis. (HEPATOLOGY 2006;44:1555-1563

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

“…Two control samples were included in each Western blot, one with low expression (C1) and another with higher expression (C2), to compare densitometry analysis between different blots, as performed by ourselves previously [14]. …”

“…First, McKee et al [12] demonstrated the presence of different transporters in the urine of rats, and later, Pisitkun et al [13] detected them in humans. One of the major pathways by which apical membrane proteins are excreted in the urine seems to be by exosome release [14,15,16,17]. Exosomes are small membrane-bound vesicles that originate as the internal vesicles of multivesicular bodies.…”

Hyponatremia and other electrolyte/ion disorders

“…AVP stimulates the translocation of aquaporin-2 from sub-apical multivescicular bodies to the apical membrane [13]. According to this pathogenetic interpretation of hyponatremia in cirrhosis, urinary excretion of aquaporin-2 would be expected to be increased and not reduced as was found by Esteva-Font et al [14]. The authors found urinary aquaporin-2 excretion in patients with cirrhosis and hyponatremia lower than in patients without hyponatremia and did not find a correlation between plasma level of AVP and urinary aquaporin-2 excretion.…”

“…The authors found urinary aquaporin-2 excretion in patients with cirrhosis and hyponatremia lower than in patients without hyponatremia and did not find a correlation between plasma level of AVP and urinary aquaporin-2 excretion. Nevertheless, the reduced urinary excretion of aquaporin-2 in patients with cirrhosis and hyponatremia may represent the molecular basis of the phenomenon of escaping the effects of AVP similar to that found in healthy subjects [14]. In fact, if the AVP-aquaporin-2 system was persistently activated in cirrhosis, solute-free water reabsorption would be permanently increased relative to sodium retention, and serum sodium levels would decline steadily to levels incompatible with life.…”

Screening for Kidney Cancer: Is There a Role for Aquaporin-1 and Adipophilin?

“…For example, tubular expression and levels of urinary excretion of AQP2 vary 5-to 6-fold depending on the hydration state of a person. 10 Granted, unlike AQP1, AQP2 is regulated by antidiuretic hormone, but this still illustrates the point that a good deal more work needs to be done, both in healthy volunteers under different conditions and in patients with a variety of illnesses of the kidneys, heart, and liver. In contrast, it seems irrefutable that the patients with tumors had much higher urine concentrations of AQP1 and ADFP, and that these were most likely caused by the tumors, as levels declined profoundly after treatment.…”