Digital pathology in nephrology clinical trials, research, and pathology practice

Abstract

Purpose of review: In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine.

Recent findings: Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases.

Summary: The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

FIGURE 1

Overall workflow to establish a DPR.

FIGURE 2

Virtual microscopy in clinical practice: telepathology (left panel) is used to evaluate frozen sections from cadaveric kidney transplant preimplantation. Frozen sections from a wedge biopsy is viewed with microscope connected to a camera for evaluation by a renal pathologist remotely located. Telepathology can also be used to evaluate adequacy of native and transplant kidney biopsies by placing the cores of fresh tissue on a glass slide. By using the microscope connected to a camera, the renal pathologist can remotely evaluate the percentage of cortex in the biopsy prior triaging and fixation. Whole slide images (right panel) are created from scanned glass slides, and stored in a web-accessible digital pathology repository to be shared with other renal pathologists for consultation, second opinion, or primary diagnosis (the later has still restricted use in the United States). An expert renal pathologist can access the repository remotely for visualization, assessment, and reporting of findings.

FIGURE 3

Standardization of protocols for globalization of the renal biopsy morphologic and morphometric profiles. Standardize protocols for pathology material acquisition, uploading and organization into the digital pathology repository, data collection using an electronic scoring matrix are implemented across different consortia and continents. Cross-training of investigators to implement reproducibility is performed via international webinar meetings. Adapted with permission [2^▪▪].

FIGURE 4

Podometrics. (a) The cartoon illustrates the events leading to a reduction in relative or absolute podocyte density, resulting in glomerulosclerosis. When podocytes are lost or the glomerular size increases, podocytes become hypertrophic in an attempt to maintain the filtration barrier, resulting in a decrease in podocyte density. When the threshold of hypertrophic stress and loss of adaptive capacity is reached, podocytes detach, resulting in progressive podocytopenia. (b) From a glomerulus (upper panel), measurements of tuft area (middle panel) and podocyte features (bottom panel) can be obtained from a single section stained with periodic acid–Schiff and immunohistochemistry for Wilm’s Tumor 1 by employing National Institute of Health ImageJ software. With this modified protocol based on the measurements are then used to calculate podocyte density per glomerular volume. (Histology images kindly provided by Chris O’Connor and Markus Bitzer at the University of Michigan, Division of Nephrology) [47].