A Systematic Review of Inter-Pathologist Agreement in Histological Classification of Lupus Nephritis

Abstract Introduction Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus, resulting in increased morbidity and mortality. The gold standard for diagnosis of lupus nephritis 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 inter-pathologist reproducibility in current assessment of lupus nephritis. Methods Using Pubmed and Google Scholar search engines, studies analyzing the agreement of 4 or more pathologists assessing LN slides using the ISN/RPS classification, activity index, and chronicity index were selected for analysis n this systematic review. Results In reviewing six qualifying studies (those analyzing the agreement of four or more pathologists using the ISN/RPS classification, activity index, and chronicity index) for the assignment of ISN/RPS class was 0.325 (IQR 0.2405-0.425), which is “poor”. The median inter-pathologist 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 of ISN/RPS classification system and activity and chronicity indices for lupus nephritis exhibits poor inter-pathologist agreement, which limits use in clinical practice. Since this can have severe repercussions on patient’s treatment and prognosis, efforts to update pathology assessment guidelines, objectively measurable biomarkers, and deep learning approaches are strongly warranted.