Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images.
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<kappa≤0.60) for 17 and good (0.60<kappa≤0.80) for 8, for 52% with moderate or better kappas. Clustering of glomerular descriptors based on similar pathologic features improved concordance. Concordance was independent of years of experience, and increased with webinar cross-training. Excellent concordance was achieved for interstitial fibrosis and tubular atrophy. Moderate-to-excellent concordance was achieved for all ultrastructural podocyte descriptors, with good-to-excellent concordance for descriptors commonly used in clinical practice, foot process effacement, and microvillous transformation. NEPTUNE digital pathology scoring system enables novel morphologic profiling of renal structures. For all histologic and ultrastructural descriptors tested with sufficient observations, moderate-to-excellent concordance was seen for 31/54 (57%). Descriptors not sufficiently represented will require further testing. This study proffers the NEPTUNE digital pathology scoring system as a model for standardization of renal biopsy interpretation extendable outside the NEPTUNE consortium, enabling international collaborations.
Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL, USA.
Laura
L
Barisoni
Department of Pediatrics, Division of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
Jonathan P
JP
Troost
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cynthia
C
Nast
Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Serena
S
Bagnasco
Department of Pathology, University of Toronto, Ontario, Canada, USA.
Carmen
C
Avila-Casado
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Jeffrey
J
Hodgin
Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
Matthew
M
Palmer
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Avi
A
Rosenberg
Department of Pathology, University of North Carolina, Chapel Hill, NC, USA.
Adil
A
Gasim
Department of Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Chrysta
C
Liensziewski
Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL, USA.
Lino
L
Merlino
Department of Pathology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
Hui-Ping
HP
Chien
Department of Pathology, University of Chicago, Chicago, IL, USA.
Anthony
0000-0002-6877-5510
A
Chang
Department of Pathology, Sharp Memorial Hospital, San Diego, CA, USA.
Shane M
SM
Meehan
Department of Pathology, Washington University, St. Louis, MO, USA.
Joseph
J
Gaut
Biostatistics Department, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Peter
P
Song
Department of Medicine, Division of Nephrology, University of Pennsylvania, Philadelphia, PA, USA.
Lawrence
L
Holzman
Department of Pediatrics, Division of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
Debbie
D
Gibson
Department of Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Matthias
M
Kretzler
Biostatistics Department, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Brenda W
BW
Gillespie
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Stephen M
0000-0001-8283-1788
SM
Hewitt
D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure; D007674:Kidney Diseases / Q000473:pathology*; D015203:Reproducibility of Results