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      Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments

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      1 , * , 2 , 3 , 4 , 5 , 6 , 3 , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Kidney International
      Nature Publishing Group
      glomerular diseases, IgA nephropathy, progression of chronic renal failure, proteinuria, renal pathology, risk factors

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          Abstract

          The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m 2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.

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          Most cited references32

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          Remission of proteinuria improves prognosis in IgA nephropathy.

          Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with 3 g/d (n = 121) lost renal function 25-fold faster than those with or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.
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            Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions.

            Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is an essential tool in the diagnosis and therapeutic monitoring of arterial hypertension in children. The statistical use of pediatric ABPM reference values has been compromised by the non-Gaussian distribution of 24-h blood pressure (BP) in children. To develop distribution-adjusted pediatric ABPM reference tables. From cross-sectional ABPM data obtained in 949 healthy children and adolescents aged 5-20 years, a set of reference tables was developed for 24-h, daytime and night-time mean values of systolic, diastolic, mean arterial BP and heart rate, utilizing the LMS method to account for the variably skewed distribution of ABPM data. Age- and gender-specific estimates of the distribution median (M), coefficient of variation (S) and degree of skewness (L) were obtained by a maximum-likelihood curve-fitting technique. The estimates of, and can be used to normalize ABPM data to gender and age or height. Re-application of the established, and values in the reference population confirmed appropriate normalization of ABPM values. Height standard deviation scores (SDS), body mass index (BMI) SDS and heart rate SDS were independent positive predictors of 24-h systolic BP SDS. Diastolic 24-h mean BP SDS showed a weak correlation with BMI SDS only. The use of LMS reference tables permits calculation of appropriate SDS values for ABPM in children. Whereas systolic 24-h BP is independently correlated with age, relative height and obesity, diastolic values are almost independent of age and relative height, and weakly associated with relative obesity.
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              The commonest glomerulonephritis in the world: IgA nephropathy.

              G D'Amico (1987)
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                Author and article information

                Journal
                Kidney Int
                Kidney Int
                Kidney International
                Nature Publishing Group
                0085-2538
                1523-1755
                October 2014
                02 April 2014
                : 86
                : 4
                : 828-836
                Affiliations
                [1 ]City of the Health and the Science of Turin Health Agency, Regina Margherita Children's Hospital , Turin, Italy
                [2 ]Hôpital du Sacré-Coeur de Montréal , Montreal, Canada
                [3 ]Oxford University Hospitals , Oxford, UK
                [4 ]Unversity Health Network, Toronto General Hospital , Toronto, Canada
                [5 ]Imperial College, Hammersmith Hospital , London, UK
                [6 ]University Hospitals of Leicester , Leicester, UK
                Author notes
                [* ]City of the Health and the Science of Turin Health Agency, Regina Margherita Children's Hospital , Piazza Polonia 94, 10126 Turin, Italy. E-mail: rosanna.coppo@ 123456unito.it
                [7]

                Steering committee members, responsible for manuscript preparation.

                [8]

                See appendix.

                Article
                ki201463
                10.1038/ki.2014.63
                4184028
                24694989
                90905c5e-d6ce-4c10-a7a9-a61a2a742e4c
                Copyright © 2014 International Society of Nephrology

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 11 September 2013
                : 03 December 2013
                : 02 January 2014
                Categories
                Clinical Investigation

                Nephrology
                glomerular diseases,iga nephropathy,progression of chronic renal failure,proteinuria,renal pathology,risk factors

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