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Significance Statement A higher percentage of the kidney cortex area that exhibits interstitial fibrosis/tubular atrophy (IF/TA) is a feature of poor prognosis on biopsy. This study describes IF/TA density (the number of IF/TA foci per area of cortex) and shows it predicts progressive CKD, independent of both percentage IF/TA and clinical characteristics among patients who have undergone nephrectomy. Other patterns of IF/TA and inflammation were not predictive for progressive CKD and mortality beyond percentage IF/TA and clinical characteristics. At the same percentage IF/TA, a higher IF/TA density suggests more scattered and widespread damage to the nephrons, with a worse kidney prognosis. This information may be helpful for accurate interpretation of the severity of “chronic changes” observed on a kidney biopsy. Background Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear. Methods We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for a tumor over 2000–2015, and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm 2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6–12 months. Progressive CKD was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy eGFR. Cox models assessed the risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for the percentage IF/TA and clinical characteristics. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m 2 ), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume. Conclusions Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.

Context.— It is unclear if preimplantation frozen section biopsy correlates with outcomes after deceased donor kidney transplantation. Objective.— To assess if chronic histologic changes on the preimplant frozen section correlates with graft loss and estimated glomerular filtration rate independently of kidney donor profile index (KDPI). Design.— Seven hundred three preimplantation biopsies were reviewed and a Banff sum score was calculated using glomerular sclerosis, interstitial fibrosis, vascular intimal thickening, and arteriolar hyalinosis. The posttransplant outcomes were compared for preimplantation biopsy Banff sum 0-1, 2-3, and 4-9. The cohort was also stratified by KDPI 85 or less versus more than 85. Results.— For the entire biopsy cohort, graft survival, estimated glomerular filtration rate at 1 year, and chronic changes on a 1-year posttransplant biopsy were superior in the group with preimplantation Banff sum 0-1. After stratifying by KDPI, the Banff sum no longer correlated with graft survival. In a univariate mode, using the Banff sum score as a continuous variable, a higher Banff sum score was significantly associated with graft failure (P = .03); however, after adjusting the KDPI, the Banff sum score no longer correlated with graft failure (P = .45). The 1-year estimated glomerular filtration rate and 1-year biopsy changes were superior in the group with Banff sum 0-1 only in the cohort with KDPI 85 or less. Conclusions.— In donor kidneys used for transplant, preimplantation biopsy chronic changes correlate with estimated glomerular filtration rate and biopsy findings at 1 year, but biopsies with mostly mild chronicity and Banff sum scores less than or equal to 5 did not impact graft survival beyond KDPI.

AimsMachine learning in digital pathology can improve efficiency and accuracy via prescreening with automated feature identification. Studies using uniform histological material have shown promise. Generalised application requires validation on slides from multiple institutions. We used machine learning to identify glomeruli on renal biopsies and compared performance between single and multiple institutions.Methods and resultsRandomly selected, adequately sampled renal core biopsy cases (71) consisting of four stains each (haematoxylin and eosin, trichrome, silver, periodic acid Schiff) from three institutions were digitised at ×40. Glomeruli were manually annotated by three renal pathologists using a digital tool. Cases were divided into training/validation (n = 52) and evaluation (n = 19) cohorts. An algorithm was trained to develop three convolutional neural network (CNN) models which tested case cohorts intra‐ and inter‐institutionally. Raw CNN search data from each of the four slides per case were merged into composite regions of interest containing putative glomeruli. The sensitivity and modified specificity of glomerulus detection (versus annotated truth) were calculated for each model/cohort. Intra‐institutional (3) sensitivity ranged from 90 to 93%, with modified specificity from 86 to 98%. Interinstitutional (1) sensitivity was 77%, with modified specificity 97%. Combined intra‐ and inter‐institutional (1) sensitivity was 86%, with modified specificity 92%.ConclusionsFeature detection sensitivity degrades when training and test material originate from different sites. Training using a combined set of digital slides from three institutions improves performance. Differing histology methods probably account for algorithm performance contrasts. Our data highlight the need for diverse training sets for the development of generalisable machine learning histology algorithms.

AbstractKidney transplant (KT) outcomes from high kidney donor profile index (KDPI ≥85%) donors with acute kidney injury (AKI) remain underreported. KT from 172 high KDPI Acute Kidney Injury Network (AKIN) stage 0‐1 donors and 76 high KDPI AKIN stage 2‐3 donors from a single center were retrospectively assessed. The AKIN 2‐3 cohort had more delayed graft function (71% vs. 37%, p < .001). At one year, there were no differences in the estimated glomerular filtration rate (44 ± 17 vs. 46 ± 18, p = .42) or fibrosis on protocol biopsy (ci, p = .85). Donor terminal creatinine (p = .59) and length of delayed graft function (p = .39) did not impact one‐year eGFR. There were more primary nonfunction (PNF) events in the high KDPI AKIN 2‐3 group (5.3% vs. 0.6%, p = .02). With a median follow‐up of 3.8 years, one‐year death‐censored graft failure was 3.5% for AKIN 0‐1 and 14.5% for AKIN 2‐3 (HR 2.40, 95% CI 1.24‐4.63, p = .01). Although AKIN stage 2‐3 high KDPI kidneys had comparable one‐year eGFR to AKIN stage 0‐1 high KDPI kidneys, there were more PNF occurrences and one‐year death‐censored graft survival was reduced. Given these findings, additional precautions should be undertaken when assessing and utilizing kidneys from severe AKI high KDPI donors.

ObjectivesTo determine whether renal transplant diagnoses substantially change when 2 biopsy sites are chosen and whether contrast‐enhanced ultrasound (CEUS) has value for targeting the second site.MethodsWe prospectively enrolled 40 patients undergoing ultrasound‐guided renal transplant biopsy within 2 years of transplant: 20, surveillance; and 20, for cause. A CEUS examination was performed to identify cortical regions with subjectively altered flow. One biopsy was performed at the operator‐preferred (primary) site regardless of CEUS findings. Another biopsy was done at a second location, either targeted to an area in which CEUS perfusion findings differed from the primary site (targeted) or at a random location (secondary) if no other area differed. Specimens were randomly labeled A or B; pathologists were blinded to the CEUS result and biopsy location. Location‐specific CEUS assessments were recorded. Pathologic results were compared, including acute and chronic Banff scores and any new findings from the targeted or secondary biopsy.ResultsForty patients were enrolled between January 2016 and December 2018. No location‐specific pathologic differences correlated with differences in CEUS assessments. The second biopsy provided additional information that changed management in 4 of 40 patients (10.0% [95% confidence interval, 2.8%–23.7%]). Major bleeding complications occurred in 3 of 40 (7.5%) patients.ConclusionsContrast‐enhanced ultrasound targeting was not useful. Major bleeding complications were higher than expected, possibly due to the additional biopsy away from the operator‐preferred location. Obtaining a second renal transplant biopsy from a substantially different area than the initial operator‐preferred location provided additional clinically useful information in 10% of patients.

Context.— Idiopathic pulmonary fibrosis is a clinical syndrome characterized by the presence of usual interstitial pneumonia (UIP) radiologically and pathologically. Per consensus criteria adopted in 2011, diagnosis of idiopathic pulmonary fibrosis no longer requires a biopsy in an appropriate context if UIP is seen on imaging. As a result, lung biopsies are now typically reserved for patients having indeterminate clinical or imaging findings or suspicion for alternative diagnoses, but the impact of updated guidelines on pathology practice remains unclear. Objective.— To determine the frequency of histologic UIP before and after 2011. Design.— Surgical lung biopsies from adults were studied within two 4-year periods: July 1, 2006 through June 30, 2010 and January 1, 2012 through December 31, 2015. Pathology slides were reviewed in a fashion blinded to clinical information and were classified using current guidelines. Results.— Biopsies from 177 and 86 patients (mean [SD] age, 62 [12] and 59 [14] years; 50.3% [89 of 177] and 48.8% [42 of 86] men) before and after 2011, respectively, were reviewed. Probable UIP or UIP was less-frequently encountered after 2011 in all patients with fibrosis (9 of 54 [16.7%] versus 41 of 119 [34.5%] before 2011, P = .02) and also in patients 50 years old and older (8 of 46 [17.4%] versus 39 of 109 [35.8%] before 2011, P = .02), with a concomitant rise in cases indeterminate for UIP or showing alternative diagnoses. Conclusions.— Histology for UIP is less frequently encountered in our contemporary practice compared with the historic era. The pretest probability of a non-UIP diagnosis is now high, even in elderly patients, underscoring the need for pathologists to be familiar with the histologic features of alternative diagnoses.

Context.— Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) requires multidisciplinary diagnosis that includes clinical, radiologic, and often pathologic assessment. In 2018, the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society (ATS/ERS/JRS/ALAT) and the Fleischner Society each published guidelines for the diagnosis of IPF, which include criteria for 4 categories of confidence of a histologic usual interstitial pneumonia (UIP) pattern. Objective.— To (1) identify the role of the guidelines in pathologic assessment of UIP; (2) analyze the 4 guideline categories, including potential areas of difficulty; and (3) determine steps the Pulmonary Pathology Society and the greater pulmonary pathology community can take to improve current guideline criteria and histopathologic diagnosis of interstitial lung disease. Data Sources.— Data were derived from the guidelines, published literature, and clinical experience. Conclusions.— Both guidelines provide pathologists with a tool to relay to the clinician the likelihood that a biopsy represents UIP, and serve as an adjunct, not a replacement, for traditional histologic diagnosis. There are multiple challenges with implementing the guidelines, including (1) lack of clarity on the quantity and quality of histologic findings required, (2) lack of recognition that histologic features cannot be assessed independently, and (3) lack of guidance on how pathologists should incorporate clinical and radiographic information. Current criteria for “probable UIP” and “indeterminate for UIP” hinder accurate reflection of the likelihood of IPF. These challenges highlight the need for further morphologic-based investigations in the field of pulmonary pathology.