Urine and plasma levels of uroguanylin and its molecular forms in renal diseases

Abstract

Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl- secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 +/- 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 +/- 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl-, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10 kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin.

Cellular Effects of Guanylin and Uroguanylin

“…More than 11 yr ago, Nakazato et al (82) showed that human GN increases in patients who have chronic renal failure and undergo hemodialysis. The UGN concentration in plasma and/or in urine is increased in patients with chronic renal failure and glomerulonephritis and in patients on hemodialysis (52,(83)(84)(85). In patients with nephrotic syndrome, UGN plasma concentration was higher and urinary concentration was lower compared with values in healthy volunteers (84).…”

“…UGN is expressed in the kidney, and its expression is higher in animals that are on a high-salt diet (53,54). It is still not clear whether the increase in the urinary concentrations of UGN and cGMP (52,53) are due to local production and secretion of UGN within the kidney or to filtration in the glomerulus. Both GN and UGN circulate in the plasma and can be filtered in the glomerulus into the primary urine.…”

“…Thus, the action of UGN in the kidney can be endocrine (produced in the intestine with actions in the kidney), paracrine (produced by the kidney), or both. Kinoshita et al (52) showed higher UGN concentration in blood and urine of individuals who were on a high-salt diet compared with those who were on a low-salt diet, which speaks in favor of an endocrine function of UGN. Recently, Fukae et al (53) showed that rats that are fed a high-salt diet have higher UGN and cGMP concentrations in the urine but show no changes in the concentration of UGN in the plasma compared with control animals.…”

Guanylins - Agents with natriuretic effect

“…The plasma uroguanylin correlated with serum creatinine (r = 0.71, P < 0.001). 10 A different study found that a diet high in salt leads especially to increased guanylin secretion (3 times), less uroguanylin secretion. Also the application of hyperosmolar manitole leads to a smaller, but still significant increase in guanylin secretion.…”

“…kidney or liver). 3,10 EFFECTS OF GUANYLIN AND UROGUANYLIN Uroguanylin and guanylin are peptides which influence the production of cGMP in enterocytes (and other tissues -see above) by activation of apical membrane, when the activation of guanylat cyclase takes place. Presumably these hormones play a role in the so-called "intestinalkidney axis", which directly influences the regulation of salt and water homeostasis.…”