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      Changes in Urinary Levels and Renal Expression of Uroguanylin on Low or High Salt Diets in Rats

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          Background: The novel peptide, uroguanylin, is mainly produced in the intestine and causes natriuresis via cyclic GMP (cGMP) activation. Uroguanylin plays an important role in sodium transport in the gastrointestinal tract and functions as an intestinal natriuretic hormone during oral salt load. However, the role and behavior of uroguanylin in the kidneys during high salt load remains unknown. Methods: We measured the uroguanylin concentrations in the urine and plasma of rats fed with low or high salt diets for 1 week, using a sensitive radioimmunoassay (RIA). Urinary cGMP and electrolyte excretion was also measured. Intestinal and renal expression of uroguanylin mRNA was evaluated by Northern blotting and by reverse transcription-polymerase chain reaction (RT-PCR). Results: The urinary excretion of immunoreactive (ir-) uroguanylin in rats on the high salt diet was significantly higher than that in the low salt group (425 ± 107 vs. 128 ± 8.5 pmol/day, p < 0.01) and significantly correlated with urinary Na<sup>+</sup> and cGMP excretion. Plasma ir-uroguanylin levels between the two groups did not significantly differ. Uroguanylin mRNA expression was increased both in the intestine and kidneys of rats on the high salt diet. Conclusion: These findings suggest that uroguanylin regulates sodium metabolism in the intestine and kidneys during oral salt load in an autocrine and paracrine manner.

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          Plasma and Urine Levels of Uroguanylin, a New Natriuretic Peptide, in Nephrotic Syndrome

          Uroguanylin, a new natriuretic peptide originally isolated from urine, stimulates the membrane guanylate cyclase C receptor. No information, however, is available on the plasma and urine levels of uroguanylin in nephrotic syndrome (NS), the state associated with sodium and water retention. Using a sensitive radioimmunoassay, we measured the plasma and urine concentrations of immunoreactive (ir-)uroguanylin in NS patients and compared them with those of patients with non-nephrotic glomerulonephritis. Plasma ir-uroguanylin, blood pressure and the cardiothoracic ratio were higher, and urine excretion of ir-uroguanylin was lower in the NS patients. Plasma ir-uroguanylin in the NS patients significantly decreased during remission as compared with findings on admission. There was a significant inverse correlation between the concentration of plasma ir-uroguanylin and that of serum total protein or albumin. Moreover, fluid retention in the NS patients was correlated with the changes in plasma ir-uroguanylin between admission and remission, indicative that the plasma concentration increases with the severity of the nephrotic state. Taking into account its potent natriuretic effect, these findings suggest that uroguanylin may function in the pathophysiological mechanism in NS.
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            Plasma Concentration of Uroguanylin in Patients on Maintenance Dialysis Therapy

            Background: Uroguanylin, originally isolated from urine, is a new natriuretic peptide. Its plasma level is increased in association with renal impairment and fluid retention in patients with renal diseases. Methods: Uroguanylin concentrations were measured in patients on hemodialysis (HD, n = 76) and those on continuous ambulatory peritoneal dialysis (CAPD, n = 10) using a sensitive ra- dioimmunoassay for human uroguanylin. Results: Plasma concentrations of immunoreactive (ir)-uroguanylin in the patients on HD and CAPD (212.0 ± 17.4 and 245.3 ± 39.5 fmol/ml) were significantly higher than the value for the normal controls (5.0 ± 0.3 fmol/ml). Plasma ir-uroguanylin levels before the start of regular HD were correlated with predialysis excess weight based on their dry weights (r = 0.33, p < 0.01) and with dialysis duration (r = 0.26, p < 0.05). The plasma levels in patients with HD, for whom high-flux membranes were used, were decreased at the end of regular HD as compared with the prior levels (p < 0.05), but not in those who underwent HD with conventional membranes. Conclusion: These findings suggest that the plasma ir-uroguanylin level is related to the patient’s volume status as well as renal impairment. Whether the accumulation of uroguanylin has a pathological effect has yet to be determined.
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              Immunohistochemical Localization of Uroguanylin in the Human Kidney


                Author and article information

                S. Karger AG
                October 2002
                02 September 2002
                : 92
                : 2
                : 373-378
                aFirst and bThird Departments of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan
                63311 Nephron 2002;92:373–378
                © 2002 S. Karger AG, Basel

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                Figures: 3, References: 26, Pages: 6
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