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

Abstract

IntroductionLupus 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.MethodsUsing 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.ResultsIn 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.ConclusionThus, 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.

Digital pathology and computational image analysis in nephropathology

“…The digital ecosystem has the potential to facilitate the harmonization of data collection both within and between consortia via the use of shared protocols 10 , and to improve accuracy 15 and concordance among pathologists 12,16 . However, agreement among nephropathologists in diagnostic and tissue assessment remains the limiting factor and a pre-requisite for the training of AI algorithms 5,12,16,[70][71][72][73] . Awareness that the standardization of pathology definitions and use of a controlled vocabulary are central elements that drive the reproducibility and accuracy of observations and/or of data generated for both human and computer-aided analysis is reflected by several recent initiatives.…”

“…Similarly, the percentage of interstitial fibrosis was associated with the expression of specific genes, transcriptional regulators and urinary biomarkers across cohorts from North America and Europe 54,55 . However, visual (that is, manual) assessment of WSIs is time consuming and has limited reproducibility 71 . Computational imaging algorithms are likely to provide more efficient and reproducible automated quantitative assessment across diseases and populations, increasing the robustness of the observations and scalability of such studies.…”

“…3 ). For example, automated detection of histological primitives has potential operational applications owing to its ability to increase the reproducibility of estimates of the distribution, severity and quantity of structures and lesions that are known predictors of outcome or molecular signatures but which have limited reproducibility when assessed manually (for example, globally sclerotic glomeruli, interstitial fibrosis, diabetic glomerulosclerosis stage) 4 , 5 , 12 , 16 , 71 ; and to provide a quantitative estimate of histological primitives that can be visualized but cannot be reliably counted manually (for example, podocytes, interstitial capillaries) 98 , 100 – 104 . Thus, DL quantification of these histological primitives can augment the ability of the pathologist to interpret and diagnose kidney diseases.…”

Lupus Nephritis: Renal Biopsy Guiding the Clinician

“…The role of the renal biopsy in diagnosis, treatment, management, and follow-up of LN is critical, although to predict the outcome has been a matter of controversy [1,7,8]. Considering the importance of the biopsy making the treatment decision and determining the prognosis, it is essential to assess renal histopathology with high accuracy [9,12,13]. LN can affect all compartments of the kidney including glomeruli, tubules, interstitium and blood vessels.…”

Diagnostic value of urinary monocyte chemoattractant protein-1 in evaluating the activity of lupus nephritis: a meta-analysis

“…3 Not only can a renal biopsy directly observe the renal lesions, it can determine the degree of kidney damage, as well as determine the activity and chronic degree of the lesion, providing a reliable basis for the development and adjustment of clinical treatment programmes. 4 Despite this, the course of LN is prolonged, and the active and stationary phases can be repeated and alternated. As a traumatic diagnostic tool, renal biopsy is difficult to read multiple times and will increase the operational risk.…”