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      Reduced Urinary Excretion of Dopamine and Metabolites in Chronic Renal Parenchymal Disease

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          Abstract

          Background: Chronic renal parenchymal diseases are accompanied by a progressive loss of tubular units endowed with the ability to synthesise dopamine from L-3,4-dihydroxyphenylalanine ( L-DOPA), and preliminary evidence has suggested that the urinary excretion of free dopamine may be reduced in these disorders. However, it is well recognised now that under in vitro conditions, dopamine newly synthesised in tubular epithelial cells undergoes extensive deamination to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO); a small amount of the amine is converted to homovanillic acid by both MAO and catechol-O-methyltransferase (COMT) and a minor amount is methylated to 3-methoxytyramine. Aims: The present study aimed at examining the relationship between renal function and daily urinary levels of L-DOPA, free dopamine and its main metabolites, DOPAC and homovanillic acid (HVA) in patients (n = 28) with chronic renal parenchymal disease, in conditions of controlled sodium, potassium and phosphate intake. The levels of 5-hydroxyindolacetic acid (5-HIAA) were also evaluated in the same cohort of patients. Results: The patients were divided in two groups according to creatinine clearance (group 1, 39±6 ml/min/1.73 m<sup>2</sup>, n = 14; group 2, 139±6 ml/min/1.73 m<sup>2</sup>, n = 14). In patients of group 1, the urinary levels of L-DOPA, dopamine and DOPAC (in nmol/24 h) were significantly lower (60% reduction) than in patients of group 2 ( L-DOPA, 134±36 vs. 308±51; dopamine, 759± 175 vs. 1,936± 117; DOPAC 2,595±340 vs. 7,938±833). Also, the urinary excretion of HVA in patients group 1 was significantly lower (40% reduction) than in patients of group 2 (17,434±2,455 vs. 27,179±2,271 nmol/24 h). By contrast, no significant difference was observed in daily urinary excretion of 5-HIAA between the two groups of patients (group 1, 27,280±3,721 nmol/day; group 2, 28,851±2,854 nmol/day). A positive linear relationship was found in these 28 patients between the creatinine clearance and the daily urinary excretion of L-DOPA (r = 0.64, p < 0.001), free dopamine (r = 0.83; p < 0.0001), DOPAC (r = 0.86; p < 0.0001) and HVA (r = 0.65; p < 0.002), but not with that of 5-HIAA (r = 0.14; ns). The U<sub>dopamine/ L-DOPA</sub> and U<sub>DOPAC/dopamine</sub> ratios were found to be similar in both groups of patients, whereas the U<sub>HVA/DOPAC</sub> ratios in patients of group 1 were found greater than in group 2 (p < 0.05). Conclusion: Patients suffering from chronic parenchymal disease with a compromised renal function present with a reduced activity of their renal dopaminergic system which correlates well with the degree of deterioration of renal function. The reduced urinary dopamine output in renal insufficiency is not attributable to enhanced metabolism of renal dopamine. We suggest that the urinary levels of DOPAC may represent a useful parameter for the assessment of renal dopamine synthesis.

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          Production of urine free dopamine from DOPA; a micropuncture study.

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            Author and article information

            Journal
            KBR
            Kidney Blood Press Res
            10.1159/issn.1420-4096
            Kidney and Blood Pressure Research
            S. Karger AG
            1420-4096
            1423-0143
            1998
            1998
            17 June 1998
            : 21
            : 1
            : 59-65
            Affiliations
            aDepartment of Nephrology, bInstitute of Pharmacology and Therapeutics, cDepartment of Pediatrics, Faculty of Medicine, Porto, Portugal
            Article
            25844 Kidney Blood Press Res 1998;21:59–65
            10.1159/000025844
            9661138
            © 1998 S. Karger AG, Basel

            Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

            Page count
            Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/25844
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