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      Urinary Liver-Type Fatty Acid-Binding Protein: Discrimination between IgA Nephropathy and Thin Basement Membrane Nephropathy

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          Abstract

          Background: Microscopic hematuria without proteinuria is a common clinical finding in cases of immunoglobulin A (IgA) nephropathy and of thin basement membrane nephropathy. Liver-type fatty acid-binding protein (L-FABP) is expressed in renal proximal tubules and is reported to be a useful marker of the progression of chronic glomerulonephritis. Aim: To assess urinary L-FABP levels for differential diagnosis in patients with microscopic hematuria but without proteinuria. Methods: This was a multi-center retrospective study. Thirty adult patients who underwent renal biopsy for microscopic hematuria and 20 healthy adult volunteers were included in this study. Urinary L-FABP levels were measured by enzyme-linked immunosorbent assay and compared, particularly between those diagnosed with IgA nephropathy and those diagnosed with thin basement membrane nephropathy. Results: Twelve (40%) patients had IgA nephropathy, 6 (20%) had thin basement membrane nephropathy and 12 (40%) had normal biopsy findings. The urinary L-FABP level was significantly higher in patients with IgA nephropathy (38.4 ± 26.8 µg/g Cr) than in healthy subjects (5.8 ± 4.0 µg/g Cr) (p < 0.01); however, the level in patients with thin basement membrane nephropathy or normal biopsy results was comparable to that in healthy subjects. Follow-up data were available for 11 of the 12 patients with IgA nephropathy who initially had no proteinuria. After 24 months, 4 of the 11 were found to have proteinuria, and the urinary L-FABP level had increased from 40.6 ± 30.5 µg/g Cr to 58.8 ± 40.5 µg/g Cr (p < 0.01). Conclusions: Our data suggest that the urinary L-FABP level can be used to discriminate between IgA nephropathy and thin basement membrane nephropathy in patients with microscopic hematuria.

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          Most cited references 6

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          Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors.

           G D'Amico (2000)
          Idiopathic immunoglobulin A nephropathy is characterized by an extreme variability in clinical course and sometimes by the unpredictability of the ultimate outcome. Among the numerous studies published in the last 15 years that have calculated the actuarial renal survival and tried to individuate the prognostic role of the clinical and histological features present at the onset of the disease or the time of biopsy, we chose to analyze critically the results of the most valid (30 studies). Actuarial renal survival at 10 years in adults was between 80% and 85% in most of the European and Asian studies, but it was less in studies from the United States and exceeded 90% in the few studies of children. Concordance existed in this selected literature that impairment of renal function, severe proteinuria, and arterial hypertension are the strongest and more reliable clinical predictors of an unfavorable outcome. However, analysis of the prognostic value of morphological lesions was more difficult because they have been characterized in some studies using an overall score or histological classes of progressively more severe involvement and, in others, using a semiquantitative grading of individual glomerular, tubular, interstitial, and vascular changes. In adult patients, a high score of glomerular and tubulointerstitial lesions, corresponding to classes IV and V of the Lee or Haas classifications, predicted a more rapid progression. When single lesions were analyzed separately, glomerulosclerosis and interstitial fibrosis appeared to be the strongest, most reliable predictors of unfavorable prognosis. More controversial was the role of crescents and capsular adhesions. None of the immunohistological features was found to be a risk factor for progression in the more accurate statistical analyses. The same histological features predicted outcome in children, although the severity of lesions at the time of biopsy was usually less than that in adults. However, in the single patient, even the evaluation of these prognostic markers sometimes fails to correctly predict outcome, probably because of the heterogeneity of the disease and the discontinuous activity of some injuring mechanisms during its course.
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            Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee's glomerular grading system.

            The glomerular grading system is useful to compare biopsy specimens and to predict the natural course of disease in IgA nephropathy (IgAN), although no grading system can be perfect. H. S. Lee's grading system for IgAN was refined as follows: grade I, normal or focal mesangial cell proliferation; grade II, diffuse mesangial cell proliferation, or 75% of glomeruli with Cr/SS/GS. This refined H. S. Lee grading system was then tested for clinical relevance on 187 patients with IgAN followed up for an average of 6.5 years (minimum, 3 years). In the survival analysis, a modified primary end-point (progressive renal disease) was used. The glomerular grades were significantly related to hypertension, serum creatinine levels and the amounts of proteinuria at time of biopsy. By univariate analysis, glomerular grades, hypertension, renal insufficiency and significant proteinuria (> or =1 g/day) were significantly associated with progressive renal disease. By multivariate analysis using the Cox regression model, glomerular grades, renal insufficiency and significant proteinuria were independent prognostic factors for progressive renal disease. At the end of follow-up, glomerular grades were significantly related to serum creatinine levels, amounts of proteinuria, hypertension and progressive renal disease. These findings indicate that the refined H. S. Lee grading system for IgAN is useful in assessing the patients' clinical outcome and is sufficiently simple and easy to reproduce as to be universally applicable in prognostic work.
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              Urinary fatty acid–binding protein as a new clinical marker of the progression of chronic renal disease

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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2005
                October 2005
                12 October 2005
                : 25
                : 5
                : 447-450
                Affiliations
                aDepartment of Medicine, Shinmatsudo Central General Hospital, Chiba, bResearch Unit for Organ Regeneration, Riken Kobe Institute, Hyogo, and cDepartment of Medicine, Koto Hospital, Tokyo, Japan
                Article
                87826 Am J Nephrol 2005;25:447–450
                10.1159/000087826
                16118482
                © 2005 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
                Tables: 2, References: 11, Pages: 4
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87826
                Categories
                Original Report: Patient-Oriented, Translational Research

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