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      Random Spot Urine Protein/Creatinine Ratio Is Unreliable for Estimating 24-Hour Proteinuria in Individual Systemic Lupus Erythematosus Nephritis Patients

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          Abstract

          Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic lupus erythematosus (SLE) glomerulonephritis (GN). Shortly afterward, 2 works were published, designated Study 1 and Study 2, which are the only studies to test spot P/C in SLE GN. Here we evaluate Study 1 and Study 2, which came to different conclusions. Methods: Study 1 compared spot P/C to the P/C of intended 24-hour collections >50% complete, which reliably estimates 24-hour proteinuria. Study 2 compared spot P/C to the protein content of intended 24-hour collections >80% complete. To compare studies, Study 2 data were converted to P/C ratios. Results: Study 1 and Study 2 were found to be in agreement. Both showed that spot P/C and 24-hour P/C were highly correlated, but only when compared over the entire P/C range (0–8.0) (r = 0.842). Over the P/C range 0.5–3.0 (the most common P/C range encountered in SLE GN), correlation was present, but concordance was poor, rendering random P/C ratio unreliable. Conclusions: Random spot P/C ratio is unreliable for detecting moderate proteinuria change. For example, random spot P/C would not reliably diagnose British Isles Lupus Assessment Group (BILAG) Category A or B proteinuric flares.

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          Use of single voided urine samples to estimate quantitative proteinuria.

          Quantitation of urinary protein excretion is used extensively for diagnostic and prognostic purposes and to assess the effects of therapy. The method most commonly used to measure urinary protein relies on 24-hour urine collections, which are time consuming, cumbersome, and often inaccurate. We reasoned that the urinary protein/creatinine ratio in a single voided urine sample should correlate well with the quantity of protein in timed urine collections. In a study of 46 specimens we found an excellent correlation between the protein content of a 24-hour urine collection and the protein/creatinine ratio in a single urine sample. The best correlation was found when samples were collected after the first voided morning specimen and before bedtime. We conclude that the determination of the protein/creatinine ratio in single urine samples obtained during normal daylight activity, when properly interpreted by taking into consideration the effect of different rates of creatinine excretion, can replace the 24-hour urine collection in the clinical quantitation of proteinuria. In the presence of stable renal function, a protein/creatinine ratio of more than 3.5 (mg/mg) can be taken to represent "nephrotic-range" proteinuria, and a ratio of less than 0.2 is within normal limits.
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            First morning voids are more reliable than spot urine samples to assess microalbuminuria.

            Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives--measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)--in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample. Regression analysis showed that the ACR in a first morning void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the prevalence was higher when determined by spot urine samples (25.4% for UAC and 22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients of variation of the ACR in a first morning void and 24-h UAE were similar (19%). Intraindividual coefficients of variations of all other measurements of albuminuria were significantly greater. In conclusion, measurement of albuminuria in a first morning void, preferably as the ACR, is more reliable than a spot urine sample to diagnose and monitor microalbuminuria.
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              The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials.

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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2009
                October 2009
                12 August 2009
                : 113
                : 3
                : c177-c182
                Affiliations
                Departments of aInternal Medicine, bStatistics and cPediatrics, The Ohio State University, Columbus, Ohio, USA
                Article
                232599 PMC2821433 Nephron Clin Pract 2009;113:c177–c182
                10.1159/000232599
                PMC2821433
                19672116
                613d24a7-f372-40b6-a350-7fce54c909b1
                © 2009 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.

                History
                : 27 January 2009
                : 18 March 2009
                Page count
                Figures: 3, Tables: 1, References: 27, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                SLE glomerulonephritis,Proteinuria,SLE flare
                Cardiovascular Medicine, Nephrology
                SLE glomerulonephritis, Proteinuria, SLE flare

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