German recommendations for pretransplantation donor kidney biopsies.

PURPOSE: This manuscript reviews the data about the histopathologic and develops recommendations to standardise and improve the biopsy procedure, the biopsy handling, the histopathological evaluation, the communication of results and the collection of data from pretransplantation kidney biopsies of deceased donors in Germany. METHODS: The recommendations are based on this literature review, on discussions at two workshops held by the German Society of Pathology and the German Organ Transplantation Foundation and on personal experiences of the authors. RESULTS: These German recommendations advocate the use of punch biopsies, paraffin embedding and detailed descriptive reporting of histopathological findings. CONCLUSIONS: These recommendations constitute only a starting point. Periodical revisions will help to simplify and optimise the recommendations with the ultimate goal to prospectively gather data for the elaboration of a computer-based algorithm that allows the exact prediction of transplantation outcome for a given match of donor and recipient.

Is the Kidney Donor Risk Index a step forward in the assessment of deceased donor kidney quality?

The allocation of deceased donor kidneys has become more complex because of the increasing spectrum of donors and recipients age and comorbidities. Several scoring systems have been proposed to evaluate the donor quality of deceased donor kidneys, based on clinical, pathological or combined parameters to predict the risk of renal allograft failure. Nonetheless, besides the dichotomous extended criteria donor (ECD) score, none of the others have been used in clinical practice because of numerous reasons, ranging from lack of robust validation to the technical challenges associated with the evaluation of donor biopsies. Recently, the Kidney Donor Risk Index (KDRI) and Profile Index (KDPI) were introduced in the USA as a refined version of the ECD score. This scoring system is based on 10 donor factors, therefore providing a finely granulated evaluation of donor quality without the need of a kidney biopsy.Here, we review the advantages and drawbacks of the main scoring systems, and we describe the components of the KDRI and KDPI. It is an easily accessible online tool, based solely on donor factors readily available at the moment of the donor offer. Importantly, the KDPI has also been made part of the 'longevity matching' allocation in the USA, where the best kidneys are allocated to the recipients with the longest predicted post-transplant survival. The KDRI should provide us with a robust qualitative evaluation of deceased donor quality, and therefore will probably play a role in deceased donor kidney allocation policies across Europe in the near future. Hopefully, the KDRI and the KDPI should help transplant programmes to better allocate the scarce resource of deceased donor kidneys.

Deep learning segmentation of glomeruli on kidney donor frozen sections.

Purpose: Recent advances in computational image analysis offer the opportunity to develop automatic quantification of histologic parameters as aid tools for practicing pathologists. We aim to develop deep learning (DL) models to quantify nonsclerotic and sclerotic glomeruli on frozen sections from donor kidney biopsies. Approach: A total of 258 whole slide images (WSI) from cadaveric donor kidney biopsies performed at our institution ( n = 123 ) and at external institutions ( n = 135 ) were used in this study. WSIs from our institution were divided at the patient level into training and validation datasets (ratio: 0.8:0.2), and external WSIs were used as an independent testing dataset. Nonsclerotic ( n = 22767 ) and sclerotic ( n = 1366 ) glomeruli were manually annotated by study pathologists on all WSIs. A nine-layer convolutional neural network based on the common U-Net architecture was developed and tested for the segmentation of nonsclerotic and sclerotic glomeruli. DL-derived, manual segmentation, and reported glomerular count (standard of care) were compared. Results: The average Dice similarity coefficient testing was 0.90 and 0.83. And the F 1 , recall, and precision scores were 0.93, 0.96, and 0.90, and 0.87, 0.93, and 0.81, for nonsclerotic and sclerotic glomeruli, respectively. DL-derived and manual segmentation-derived glomerular counts were comparable, but statistically different from reported glomerular count. Conclusions: DL segmentation is a feasible and robust approach for automatic quantification of glomeruli. We represent the first step toward new protocols for the evaluation of donor kidney biopsies.

Pre-implantation kidney biopsy: value of the expertise in determining histological score and comparison with the whole organ on a series of discarded kidneys.

BACKGROUND: Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. METHODS: 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. RESULTS: Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. CONCLUSIONS: Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

The Landscape of Digital Pathology in Transplantation: From the Beginning to the Virtual E-Slide.

BACKGROUND: Digital pathology has progressed over the last two decades, with many clinical and nonclinical applications. Transplantation pathology is a highly specialized field in which the majority of practicing pathologists do not have sufficient expertise to handle critical needs. In this context, digital pathology has proven to be useful as it allows for timely access to expert second-opinion teleconsultation. The aim of this study was to review the experience of the application of digital pathology to the field of transplantation. METHODS: Papers on this topic were retrieved using PubMed as a search engine. Inclusion criteria were the presence of transplantation setting and the use of any type of digital image with or without the use of image analysis tools; the search was restricted to English language papers published in the 25 years until December 31, 2018. RESULTS: Literature regarding digital transplant pathology is mostly about the digital interpretation of posttransplant biopsies (75 vs. 19), with 15/75 (20%) articles focusing on agreement/reproducibility. Several papers concentrated on the correlation between biopsy features assessed by digital image analysis (DIA) and clinical outcome (45/75, 60%). Whole-slide imaging (WSI) only appeared in recent publications, starting from 2011 (13/75, 17.3%). Papers dealing with preimplantation biopsy are less numerous, the majority (13/19, 68.4%) of which focus on diagnostic agreement between digital microscopy and light microscopy (LM), with WSI technology being used in only a small quota of papers (4/19, 21.1%). CONCLUSIONS: Overall, published studies show good concordance between digital microscopy and LM modalities for diagnosis. DIA has the potential to increase diagnostic reproducibility and facilitate the identification and quantification of histological parameters. Thus, with advancing technology such as faster scanning times, better image resolution, and novel image algorithms, it is likely that WSI will eventually replace LM.

Making Procurement Biopsies Important Again for Kidney Transplant Allocation.

CONTEXT: Results of procurement biopsies often drive the decision to discard kidneys from deceased donors with advanced age or comorbidities. However, the criteria to perform, process, and score procurement graft biopsies are not standardized. Subject of Review: A recent retrospective, single-center study by Carpenter et al. [Clin J Am Soc Nephrol 2018; 13: 1876-1885] compared the scores obtained from 270 consecutive frozen kidney sections of biopsies at time of procurement with those of paraffin-embedded sections of biopsies at reperfusion and the correlation of both biopsy scores with graft survival. In 116 kidneys, procurement biopsies were repeated, allowing to test the reproducibility of this technique. Procurement biopsies were poorly reproducible, did not correlate with scores obtained with paraffin-embedded reperfusion biopsies, and were not significantly associated with transplant outcomes, while reperfusion biopsies provided an excellent prediction of graft survival. Based on these findings, the authors suggest "an urgent need to reexamine the role of procurement biopsies during allocation given their high resource requirements and association with discards." Second Opinion: Carpenter's paper is important because it emphasizes the crucial role of correct histological evaluation of kidney grafts to accurately predict their survival. In this study, procurement biopsies were frozen and read by on-call pathologists, often with no specific training in renal pathology, while reperfusion sections were paraffin embedded and scored by experienced renal pathologists at Columbia University, New York, NY, USA. This methodological difference per se represents an obvious explanation for the poor concordance between the 2 assessments. Use of wedge biopsies in procurement samples versus core-needle samples in reperfusion biopsies may further account for the discrepancies between scores even in seemingly objective measurements, such as the percentage of glomerulosclerosis. Therefore, these data should not mislead us regarding the importance of procurement biopsies to define organ suitability for transplantation. Rather, they should prompt more studies aimed at optimizing the strategies to score these samples properly for optimal organ allocation.

Donor Kidney Evaluation.

In patients with end-stage renal disease, kidney transplantation is the best means to extend survival and offer a better quality of life. The current shortage of organs available for transplantation has led to an effort to expand the kidney donor pool, including the use of nonideal donor kidneys. Assessment of the quality of the donated kidney is essential, and would facilitate the decision to transplant a potential organ or discard it. Multiple clinical and histologic parameters have been examined to evaluate the donor kidney and relate the findings to the graft outcome, but clear-cut criteria are yet to be defined.