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      Clinical importance of the updated Oxford classification in allograft IgA nephropathy

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

          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 m2, 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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            Predicting the risk for dialysis or death in IgA nephropathy.

            For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death. Copyright © 2011 by the American Society of Nephrology
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              Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases.

              IgA nephropathy (IgAN) may present with a wide variety of histologic patterns on renal biopsy, ranging from a minimal lesion to a diffuse proliferative glomerulonephritis (GN). The histologic features of 244 cases of IgAN (not including Schönlein-Hanoch nephritis) diagnosed between 1980 and 1994 were reviewed, and each case was subclassified using the following, relatively simple histologic classification scheme: subclass I (39 cases): minimal or no mesangial hypercellularity, without glomerular sclerosis; subclass II (18 cases): focal and segmental glomerular sclerosis without active cellular proliferation; subclass III (110 cases): focal proliferative GN; and subclass IV (42 cases): diffuse proliferative GN; and subclass V (35 cases): any biopsy showing > or = 40% globally sclerotic glomeruli and/or > or = 40% estimated cortical tubular atrophy or loss. Subsequent analysis of renal survival in 109 patients who underwent biopsy before or during 1992 for whom such data were available showed a strong, statistically significant correlation between histologic subclass and renal survival, with an order I, II (greatest survival) > III > IV, V. Crescents were a significant negative prognostic indicator for renal survival in subclass III (but not in subclass IV), and interstitial expansion was a negative prognostic indicator in subclasses III and IV, although the statistical significance of these were not maintained after controlling for serum creatinine at the time of biopsy. The presence of peripheral glomerular capillary deposits ultrastructurally had no prognostic significance. With respect to clinical presentation, hypertension (systolic blood pressure > or = 130 mm Hg and diastolic blood pressure > or = 90 mm Hg) and proteinuria of > or = 2.0 g/24 hr were significant negative prognostic indicators for renal survival, even when controlling for serum creatinine at the time of renal biopsy. The presence of gross hematuria correlated significantly with increased renal survival by univariate analysis, but not when controlling for serum creatinine at the time of renal biopsy. The findings of this study confirm the wide variety of clinical and histopathologic presentations of IgAN, and indicate the utility of the proposed histologic classification schema in assessing a patient's likelihood of ultimately developing end-stage renal disease.
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                Author and article information

                Journal
                American Journal of Transplantation
                Am J Transplant
                Wiley
                1600-6135
                1600-6143
                May 20 2019
                May 20 2019
                Affiliations
                [1 ]Department of Internal Medicine Seoul National University Hospital Seoul Korea
                [2 ]Department of Biomedical Sciences Seoul National University College of Medicine Seoul Korea
                [3 ]Department of Pathology Asan Medical Center University of Ulsan College of Medicine Seoul Korea
                [4 ]Department of Internal Medicine Asan Medical Center University of Ulsan College of Medicine Seoul Korea
                [5 ]Department of Surgery Asan Medical Center University of Ulsan College of Medicine Seoul Korea
                [6 ]Kidney Research Institute Seoul National University College of Medicine Seoul Korea
                [7 ]Department of Internal Medicine Seoul National University Boramae Medical Center Seoul Korea
                [8 ]Department of Surgery Seoul National University Hospital Seoul Seoul National University College of Medicine Seoul Korea
                [9 ]Transplantation Research Institute Seoul Seoul National University College of Medicine Seoul Korea
                [10 ]Department of Laboratory Medicine Seoul National University Hospital Seoul Korea
                [11 ]Department of Pathology Seoul National University Hospital Seoul Korea
                Article
                10.1111/ajt.15400
                © 2019

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