Urinary Excretion of Urodilatin in Patients With Cirrhosis

Cirrhotic patients with ascites show increased plasma levels of natriuretic peptides from cardiac origin (i.e., atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]). Urodilatin is a unique member of the natriuretic peptide family because it is exclusively synthesized in the kidney acting on a paracrine fashion in the regulation of sodium excretion. To investigate the renal production of urodilatin in cirrhosis and its relationship with other natriuretic peptides and sodium retention, urodilatin excretion and plasma levels of ANP were measured in 21 healthy subjects, 13 cirrhotic patients without ascites and 23 cirrhotic patients with ascites. Urine urodilatin was measured with a highly specific radioimmunoassay using a polyclonal antibody against human urodilatin. Patients with ascites had marked sodium retention (UNa 7 ± 2 mEq/d) as compared to patients without ascites and healthy subjects (29 ± 3 mEq/d and 34 ± 5 mEq/d, respectively, P < .001). Patients with cirrhosis and ascites had urine urodilatin excretion similar to patients without ascites and healthy subjects (82 ± 8 pmol/g, 95 ± 10 pmol/g, and 89 ± 9 pmol/ g of creatinine, respectively; not significant). In addition, immunoreactive urodilatin from cirrhotic patients with ascites and healthy subjects showed a similar chromatographic pattern. By contrast, plasma ANP levels were increased significantly in patients with ascites (29 ± 3 fmol/mL) as compared with patients without ascites or healthy subjects (14 ± 3 fmol/mL and 6 ± 1 fmol/mL, respectively; P < .01). In conclusion, urine urodilatin excretion is normal in patients with cirrhosis even in the presence of marked sodium retention. The coexistence of increased ANP levels and normal urodilatin excretion suggests that in cirrhosis both natriuretic peptides are regulated independently.