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      A Systematic Review of Interpathologist Agreement in Histologic Classification of Lupus Nephritis

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          Abstract

          Introduction

          Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), resulting in increased morbidity and mortality. The gold standard for diagnosis of LN is a renal biopsy. Considering the importance of the biopsy in determining long-term prognostication and treatment decisions, it is crucial to assess renal histopathology with utmost accuracy and precision. This review represents a systematic search of published literature to estimate the degree of interpathologist reproducibility in current assessment of LN.

          Methods

          Using the PubMed and Google Scholar search engines, studies analyzing the agreement of 4 or more pathologists assessing LN slides using the ISN/Renal Pathology Society (RPS) classification, activity index, and chronicity index were selected for analysis in this systematic review.

          Results

          In reviewing 6 qualifying studies (those analyzing the agreement of 4 or more pathologists using the ISN/RPS classification, activity index, and chronicity index) for the assignment of ISN/RPS class was 0.325 (interquartile range [IQR] 0.2405–0.425), which is “poor.” The median interpathologist concordance values for the assigned activity index and chronicity index were “moderate”: 0.52 (IQR 0.51–0.69) and 0.49 (IQR 0.36–0.58), respectively.

          Conclusion

          Thus, the current scoring using the ISN/RPS classification system and activity and chronicity indices for LN exhibits poor interpathologist agreement, which limits its use in clinical practice. Given that this can have severe repercussions on a patient’s treatment and prognosis, efforts to update pathology assessment guidelines, objectively measurable biomarkers, and deep learning approaches are strongly warranted.

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          Most cited references52

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          Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004.

          Systemic lupus erythematosus (SLE) and lupus nephritis (LN) disproportionately affect individuals who are members of racial/ethnic minority groups and individuals of lower socioeconomic status (SES). This study was undertaken to investigate the epidemiology and sociodemographics of SLE and LN in the low-income US Medicaid population.
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            Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome.

            Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.

              We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications.
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                Author and article information

                Contributors
                Journal
                Kidney Int Rep
                Kidney Int Rep
                Kidney International Reports
                Elsevier
                2468-0249
                22 June 2019
                October 2019
                22 June 2019
                : 4
                : 10
                : 1420-1425
                Affiliations
                [1 ]Department of Biomedical Engineering, University of Houston, Houston, Texas, USA
                [2 ]Houston Methodist Research Institute, Houston, Texas, USA
                Author notes
                [] Correspondence: Chandra Mohan, Department of Biomedical Engineering, University of Houston, 3605 Cullen Boulevard, Houston, Texas 77204, USA. cmohan@ 123456central.uh.edu
                Article
                S2468-0249(19)31392-0
                10.1016/j.ekir.2019.06.011
                6829183
                31701051
                2d6b7288-9372-4267-9c4d-3ff73569dbcd
                © 2019 International Society of Nephrology. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 June 2019
                : 17 June 2019
                Categories
                Clinical Research

                chronic kidney disease,glomerulonephritis,inflammation,kidney biopsy,lupus

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