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      Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis

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          GFR estimating equations in a multiethnic Asian population.

          Clinical practice guidelines recommend using equations for estimating glomerular filtration rate (GFR) in chronic kidney disease (CKD) management and research. The MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (CKD Epidemiology Collaboration) equations originally were derived from a North American population and had an ethnic coefficient adjustment for African Americans. A Chinese coefficient for the MDRD Study equation subsequently was determined, but this has not been externally validated. We compared the accuracy of the equations, evaluated the ethnic coefficients, and assessed the equations for disease staging in a multiethnic Asian population with CKD. A diagnostic test study comparing the Asian coefficient (and subgroups)-modified MDRD Study and CKD-EPI equations and a cross-sectional study assessing disease staging. 232 outpatients (52% men; 40.5% Chinese, 32% Malay, and 27.5% Indian/other) with stable CKD. Asian and ethnicity-based modifications of the MDRD Study and CKD-EPI equations. Measured GFR using 3-sample plasma clearance of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA), calculated using the slope-intercept method, with body surface area normalization (du Bois) and Brochner-Mortensen correction. Overall, the CKD-EPI equation is more accurate than the MDRD Study equation throughout the GFR range, with improved bias (median difference of estimated GFR - measured GFR) and root mean square error (P <0.001). CKD-EPI versus MDRD Study equation: bias, 1.1 ± 13.8 vs -1.0 ± 15.2 mL/min/1.73 m(2); precision, 12.1 vs 12.2 mL/min/1.73 m(2). Ethnic coefficients did not improve estimates of GFR significantly. The correctness of staging was improved using the CKD-EPI equation. All participants had CKD, but few were of European descent. The reference GFR technique was different from the original studies. The CKD-EPI is more accurate than the MDRD Study equation, particularly at higher GFRs. Therefore, we recommend adopting the CKD-EPI equation without ethnic adjustment for estimating GFR in multiethnic Asian patients with CKD. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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            Development and validation of a renal risk score in ANCA-associated glomerulonephritis

            Predicting renal outcome in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) remains a major challenge. We aimed to identify reliable predictors of end-stage renal disease (ESRD) and to develop and validate a clinicopathologic score to predict renal outcome in ANCA-associated GN. In a prospective training cohort of 115 patients, the percentage of normal glomeruli (without scarring, crescents, or necrosis within the tuft) was the strongest independent predictor of death-censored ESRD. Regression tree analysis identified predictive cutoff values for three parameters: percentage normal glomeruli (N0 >25%, N1 10 to 25%, N2  25%), and estimated glomerular filtration rate at the time of diagnosis (G0 >15 ml/min/1.73 m2, G1 ≤15 ml/min/1.73 m2). Cox regression analysis was used to assign points to each parameter (N1 = 4, N2 = 6, T1 = 2, G1 = 3 points), and the resulting risk score was used to classify predicted ESRD risk as low (0), intermediate (2 to 7), or high (8 to 11 points). The risk score accurately predicted ESRD at 36 months in the training cohort (0%, 26%, and 68%, respectively) and in an independent validation cohort of 90 patients (0%, 27%, and 78%, respectively). Here, we propose a clinically applicable renal risk score for ANCA-associated GN that highlights the importance of unaffected glomeruli as a predictor of renal outcome and allows early risk prediction of ESRD.
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              Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement.

              This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 micromol/L). One hundred patients who were enrolled in an international, randomized, clinical trial to compare plasma exchange with intravenous methylprednisolone as an additional initial treatment were analyzed prospectively. Diagnostic renal biopsies were performed upon entry into the study. Thirty-nine histologic and nine clinical parameters were determined as candidate predictors of renal outcome. The end points were renal function at the time of diagnosis (GFR0) and 12 mo after diagnosis (GFR12), dialysis at entry and 12 mo after diagnosis, and death. Multivariate analyses were performed. Predictive of GFR0 were age (r = -0.40, P = 0.04), arteriosclerosis (r = -0.53, P = 0.01), segmental crescents (r = 0.35, P = 0.07), and eosinophilic infiltrate (r = -0.41, P = 0.04). Prognostic indicators for GFR12 were age (r = -0.32, P = 0.01), normal glomeruli (r = 0.24, P = 0.04), tubular atrophy (r = -0.28, P = 0.02), intraepithelial infiltrate (r = -0.26, P = 0.03), and GFR0 (r = 0.29, P = 0.01). Fibrous crescents (r = 0.22, P = 0.03) were predictive of dialysis at entry. Normal glomeruli (r = -0.30, P = 0.01) and treatment arm (r = -0.28, P = 0.02) were predictive of dialysis after 12 mo. No parameter predicted death. Both chronic and acute tubulointerstitial lesions predicted GFR12 in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group. Plasma exchange remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately (r = -0.36, P = 0.01). Normal glomeruli were a positive predictor of dialysis independence and improved renal function after 12 mo, indicating that the unaffected part of the kidney is vital in determining renal outcome.
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                Journal
                Clinical Journal of the American Society of Nephrology
                CJASN
                American Society of Nephrology (ASN)
                1555-9041
                1555-905X
                August 07 2020
                August 07 2020
                August 07 2020
                July 28 2020
                : 15
                : 8
                : 1103-1111
                Article
                10.2215/CJN.14561119
                32723805
                1cc3036f-a920-479a-b982-7eccc788f9bd
                © 2020
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