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Interstitial fibrosis assessment by renal pathologists lacks good agreement, and we aimed to investigate its hidden properties and infer possible clinical impact. Fifty kidney biopsies were assessed by 9 renal pathologists and evaluated by intraclass correlation coefficients (ICCs) and kappa statistics. Probabilities of pathologists' assessments that would deviate far from true values were derived from quadratic regression and multilayer perceptron nonlinear regression. Likely causes of variation in interstitial fibrosis assessment were investigated. Possible misclassification rates were inferred on reported large cohorts. We found inter-rater reliabilities ranged from poor to good (ICCs 0.48 to 0.90), and pathologists' assessments had the worst agreements when the extent of interstitial fibrosis was moderate. 33.5% of pathologists' assessments were expected to deviate far from the true values. Variation in interstitial fibrosis assessment was found to be correlated with variation in interstitial inflammation assessment (r 2  = 32.1%). Taking IgA nephropathy as an example, the Oxford T scores for interstitial fibrosis were expected to be misclassified in 21.9% of patients. This study demonstrated the complexity of the inter-rater reliability of interstitial fibrosis assessment, and our proposed approaches discovered previously unknown properties in pathologists' practice and inferred a possible clinical impact on patients., (© 2023. Springer Nature Limited.)

Background: Raising evidence suggested a prognostic utility of tubulointerstitial lesions in lupus nephritis (LN). The exact prevalence of tubulointerstitial abnormalities and its predictive value among pediatric onset systemic lupus erythematous (pSLE) cases, however, remained unknown., Methods: Sixty-seven pSLE subjects diagnosed with LN with initial renal samples available were enrolled and followed for an average of 6.49 ± 3.06 years. Renal histology was evaluated according to the International Society of Nephrology/Renal Pathology Society classification, National Institute of Health classification and tubulointerstitial activity index (TIAI)., Results: Tubulointerstitial injuries were observed in 38.81% of all LN cases, including 13.33% with non-proliferative lupus nephritis (nPLN) and 46.15% of with proliferative lupus nephritis (PLN). Tubulointerstitial injuries occurred solitarily in cases with nPLN(13.33%), but always associated glomerular changes and significantly impacted renal survival (p = 0.032) among those with PLN. TIAI associated glomerular abnormalities (p = 0.031) but did not correlate renal performance or subsequent outcome (p = 0.445). Among the chronicity index, it was the chronic tubulointerstitial lesions that provided prognostic information (p = 0.012). None of the individual tubulointerstitial factors, however, reached statistical significance in end-stage renal disease prediction. Finally, considering tubulointerstitial injuries in PLN further discriminated subsequent renal outcome (p = 0.006)., Conclusion: Tubulointerstitial abnormalities were found in nearly one-third of all pediatric LN cases. With its importance in early identifying those at risk of renal failure, histologic classification considering tubulointerstitial lesions may potentially assist outcome prediction., (Copyright © 2017. Published by Elsevier B.V.)

The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen's kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40