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

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.

SUBMITTER: Dasari S

PROVIDER: S-EPMC6829183 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Dasari Shobha S Chakraborty Ashish A Truong Luan L Mohan Chandra C

Kidney international reports 20190622 10

<h4>Introduction</h4>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 de ...[more]

PMID: 31701051

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Project description:IntroductionFew studies have evaluated the economic burden of lupus nephritis (LN). The aim of this systematic literature review (SLR) was to assess the economic burden (direct and indirect costs, and healthcare resource utilization [HCRU]) associated with LN, with particular focus on the burden of renal flares and end-stage kidney disease (ESKD).MethodsThis SLR (GSK study 213531) was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the MEDLINE and Embase databases were conducted for English language publications reporting cost or HCRU data in patients with LN (regardless of age or LN histological class) until December 10, 2019. Handsearching of conference proceedings and keyword-based searches in PubMed, Google, and Google Scholar were also conducted.ResultsTwenty-two studies were identified from 28 publications reporting the cost (n = 19) and HCRU (n = 13) associated with LN. Most studies were from North America (n = 13) and many used administrative claims data (n = 9). LN was associated with substantially higher direct costs (e.g., total annual, hospitalization, and ESKD-related direct costs), total indirect costs, and HCRU (e.g., hospitalization, outpatient services, and medication use) compared with patients without systemic lupus erythematosus (SLE) or non-renal SLE controls. ESKD and dialysis were significant contributors to economic burden. No studies described the cost of renal flares.ConclusionsThe consensus across the 22 studies was that the economic burden of LN is substantial, particularly in active or severe disease, or if there is progression to ESKD. Total direct cost may be underestimated in claims data given the challenges of identifying patients with LN. Further studies are vital to ascertain the cost of renal flares; a renal flare is likely to result in a period of increased HCRU, which could be mitigated by treatments that extend renal remission.

Project description:To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined.A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, ? or intraclass correlation values were calculated. The intraclass correlation or ?-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced).Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The ?/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004).There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of a central review by experienced nephropathologists in clinical trials.

Project description:BackgroundSystemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by abnormal B-cell activation and the presence of autoantibodies, which can result in organ damage. Lupus nephritis (LN) is the most common severe organ manifestation of SLE and may result in impaired kidney function. However, there is limited research on the health-related quality of life (HRQoL) burden amongst patients with LN. The objective of this systematic literature review was to assess the HRQoL, fatigue and health utilities associated with LN.MethodsA structured literature search (GSK Study 212980) of the MEDLINE and Embase databases was conducted in July 2019 and updated September 2021. Relevant international congress abstracts from 2016 to 2021 were searched, and gray literature searches and keyword-based searches in PubMed, Google, and Google Scholar were also conducted. Results were screened according to predefined criteria and data on the outcomes of interest were extracted. A quantitative analysis was conducted to supplement the narrative review, to provide 36-item Short Form survey (SF-36) estimates, and to determine variation by prognostic factors.ResultsOf 1155 articles identified, 26 studies for a total of 3440 patients were included. Patients with LN showed poorer HRQoL and more fatigue than healthy controls/the general population, although these were similar between patients with SLE with and without LN. HRQoL was worse in patients with LN Class III/IV or with active disease. Fatigue was generally reported as the most burdensome symptom and was associated with lower HRQoL and increased treatment dissatisfaction. During induction treatment, HRQoL and fatigue were improved with mycophenolate mofetil versus cyclophosphamide. HRQoL improved over time with treatment amongst patients with active LN. Very limited data were identified assigning utilities to health states for cost-effectiveness analysis. Nine studies were considered for quantitative analysis of baseline SF-36 scores. The analysis suggested that LN has a significant impact across all SF-36 domains, with the lowest scores in the general health perceptions and role-physical domains and physical component summary.ConclusionsThere is a large HRQoL burden in patients with LN, in particular regarding symptoms of fatigue. Future research should focus on investigating fatigue severity and health utilities in LN.

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

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

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