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      Validation of the Toronto Formula to Predict Progression in IgA Nephropathy

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          Abstract

          Background/Aim: Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP<sub>0–2</sub>, UP<sub>0–2</sub>) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl<sub>0–2</sub>) would improve the predictive utility of a similar multivariate model. Methods: Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP<sub>0–2</sub>,UP<sub>0–2</sub>,slope eCrCl<sub>0–2 </sub>and predicted slope eCrCl (using the Toronto formula). Results: There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R<sup>2 =</sup> 0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75% of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R<sup>2</sup> of 0.22 (p < 0.001) and adding the slope CrCl<sub>0–2</sub> only increased this to 0.25. Conclusions: The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl<sub>0–2</sub> to a predictive model containing MAP<sub>0–2</sub>, andUP<sub>0–2 </sub>does not appear to improve prediction of the overall slope of eCrCl.

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          Most cited references 12

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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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            Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

            The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.
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              Predicting progression in IgA nephropathy.

               G Lajoie,  L Sugar,  D Cattran (2001)
              Immunoglobulin A (IgA) nephropathy is one of the most common primary types of glomerulonephritis to progress to end-stage renal disease. Its variable and often long natural history makes it difficult to predict outcome. We investigated the association of the rate of renal function decline based on the slope of creatinine clearance over time with demographic, clinical, laboratory, and histological data from 298 patients with biopsy-proven IgA nephropathy with a mean follow-up of 70 months. Using univariate analysis, urinary protein excretion at baseline and Lee pathological grading, as well as mean arterial pressure (MAP) and urinary protein excretion during follow-up, were associated with the rate of deterioration in renal function. Of these, only MAP and urinary protein excretion during follow-up were identified as independent factors by multiple linear regression analysis. The combination of best accuracy of prediction and shortest observation time using these two parameters was reached between the second and third years of follow-up. A semiquantitative method of estimating the rate of progression by using these factors was developed. These results indicate that MAP and severity of proteinuria over time are the most important prognostic indicators of IgA nephropathy. The potential relevance of the algorithm in patient management is shown.
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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
                2008
                August 2008
                25 July 2008
                : 109
                : 3
                : c148-c153
                Affiliations
                aRenal Unit, Glasgow Royal Infirmary, and bRenal Unit, Western Infirmary, Glasgow, UK; cUniversity Health Network, Toronto, Ont., Canada
                Article
                145458 Nephron Clin Pract 2008;109:c148
                10.1159/000145458
                18663327
                © 2008 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
                Figures: 3, Tables: 2, References: 14, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Blood pressure, Outcome, Progression, Proteinuria, IgA nephropathy

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