RESUMEN
Background New-onset postoperative atrial fibrillation (POAF) is the most common arrhythmia following cardiac surgery. POAF increases the risk of thromboembolism and stroke, as well as morbidity and mortality more generally. Despite evidence from the landmark PROTECT-AF and PREVAIL trials, left atrial appendage ligation (LAAL) is not routinely performed for thromboembolism prophylaxis in POAF, and anticoagulation remains the standard of care along with dual antiplatelet therapy. This study evaluated the efficacy of concomitant LAAL in eliminating the need for postoperative anticoagulation, regardless of POAF development, in patients undergoing coronary artery bypass grafting (CABG). Methods Between 2019 and 2021, 130 patients were selected to undergo concomitant LAAL while undergoing CABG surgery. Patients were then monitored for the incidence of new-onset POAF, and anticoagulation was strictly avoided for this indication. Demographic and outcome data were collected, with endpoints including transient ischemic attack (TIA) or stroke, death, and readmission within one year, as well as the length of hospital and intensive care unit (ICU) admissions. Results POAF occurred in 37 patients (28.5%), consistent with previous reports. However, none of the POAF patients experienced TIA or stroke during the one-year follow-up period, compared to 2 (2.15%) in the non-POAF group, a typical rate of postoperative stroke in such a patient population. No significant differences were observed between POAF and non-POAF cohorts in one-year stroke, all-cause mortality, readmission rates, or total hospital stay. Interestingly, the POAF cohort had a significantly longer mean ICU stay (4.24 vs 3.37 days, p = 0.0219), possibly due to the time required for arrhythmia control before discharge. The study population had a high mean CHA2DS2-VASc score (2.81), indicating an increased risk of thromboembolism, and a high mean HAS-BLED score, suggesting an elevated bleeding risk with anticoagulation. Conclusions LAAL appears to be an effective adjunct to CABG for thromboembolism prophylaxis in POAF. Formal anticoagulation was avoided in this study, with no significant differences in adverse events between POAF and non-POAF groups, suggesting that LAAL may be a suitable alternative to anticoagulation, especially in high-risk patients (e.g., those with elevated CHA2DS2-VASc or HAS-BLED scores). The safety and efficacy of this approach should be corroborated by larger randomized studies, such as the ongoing LeAAPS trial. LAAL during CABG may help reduce the risk of bleeding complications associated with anticoagulation while maintaining protection against thromboembolic events in patients who develop POAF.
RESUMEN
OBJECTIVE: Immune checkpoint inhibitor (ICI) therapies have dramatically improved outcomes in multiple cancers. ICI's mechanism of action involves immune system activation to augment anti-tumor immunity. Patients with pre-existing autoimmune diseases, such as systemic sclerosis (SSc), were excluded from initial ICI clinical trials due to concern that such immune system activation could precipitate an autoimmune disease flare or new, severe immune related adverse events (irAE). In the present study, we report our experience with ICIs in patients with pre-existing SSc. METHODS: Patients with SSc who received ICI therapy for cancer were identified from the Johns Hopkins Scleroderma Center Research Registry. Through chart review and prespecified definitions, we identified whether patients experienced worsening SSc activity or new irAEs. SSc disease activity worsening was pre-defined as an increase in modified Rodnan skin score (mRSS), new scleroderma renal crisis, progression of interstitial lung disease (ILD) on CT scan, increased Raynaud's phenomenon frequency or severity, new pulmonary hypertension, or myositis flare. IrAEs also included active inflammatory arthritis and dermatitis. RESULTS: Eight patients with SSc who received ICI therapy for cancer were included. Overall, SSc symptoms remained stable during and after ICI therapy. None of the patients with long-standing sine or limited cutaneous SSc (lcSSc) had progressive skin thickening after ICI therapy. One patient, who was early in his diffuse cutaneous SSc (dcSSc) disease course, experienced worsening skin thickening and renal crisis. Three patients (38 %) experienced a total of five irAEs (grade 2: diarrhea, mucositis and dermatitis; grade 3: pneumonitis, and grade 4: nephritis). The patient with grade 4 nephritis developed scleroderma renal crisis and immune checkpoint related nephritis simultaneously. There were no deaths due to irAEs. CONCLUSION: In this study, ICI therapy was well tolerated in patients with longstanding, sine or lcSSc. IrAE were common but generally manageable. Patients with early, active SSc may be at greater risk from ICI therapy, but more research is needed.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Esclerodermia Sistémica , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/inmunología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Anciano , Adulto , Resultado del Tratamiento , Progresión de la EnfermedadRESUMEN
Abstract Background: There are little data on the risk to a breastfeeding infant after facial botulinum toxin injections to the mother. Objective: To detect the presence of botulinum toxin in breast milk from lactating subjects treated with facial botulinum toxin injections, as measured by enzyme-linked immunosorbent assay (ELISA). Methods: For this pilot study, lactating women were injected with standardized facial botulinum toxin type A (BTXA) (range 40-92 U). Collected breast milk samples over 5 days were analyzed for the presence of botulinum toxin. Exclusion criteria included (1) lactating women still using their breast milk for their infant, (2) muscular disorders, (3) any medication that could interfere with neuromuscular function, (4) uncontrolled systemic disease, (5) pregnant, and (6) neuromodulator injection in the past 90 days. Results: Four lactating women were recruited. Eight samples had no BTXA detected, whereas 8 of the 16 total had detectible amounts, which were well below the reported lethal oral dose for an infant. Conclusion: Although the exclusion of lactating women from receiving cosmetic botulinum toxin injections is out of an abundance of caution to the theoretical risk to the infant, this study helps support the notion that facial botulinum toxin injections do not warrant an interruption in breastfeeding. Further studies with larger sample sizes are needed.
RESUMEN
Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes. Single nucleus joint RNA- and ATAC-seq sequencing offers an opportunity to study the gene regulatory networks underpinning these changes in order to identify key regulatory drivers. We develop a regularized regression approach to construct genome-wide parametric gene regulatory networks using multiomic datasets. We generate a single nucleus multiomic dataset from seven adult human kidney samples and apply our method to study drivers of a failed injury response associated with kidney disease. We demonstrate that our approach is a highly effective tool for predicting key cis- and trans-regulatory elements underpinning the healthy to failed repair transition and use it to identify NFAT5 as a driver of the maladaptive proximal tubule state.
Asunto(s)
Multiómica , Insuficiencia Renal Crónica , Adulto , Humanos , Riñón , Túbulos Renales Proximales , Células EpitelialesRESUMEN
We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery diarrhea. He was found to have Astrovirus via PCR testing in a comprehensive stool panel. The patient's home mycophenolic acid was held upon admission, while cyclosporine was continued through his hospital stay. Generally, Astroviridae infection is a rarely identified cause of enteritis and even less so in the transplant population. Although reports have been published regarding devastating cases of encephalitis in immunocompromised patients, our patient did not exhibit these symptoms and draws into question the danger of this virus in other immunosuppressed populations. This case helps to better elucidate which patient populations should be approached with caution in the setting of Astroviridae infection.
Asunto(s)
Infecciones por Astroviridae , Astroviridae , Enteritis , Trasplante de Hígado , Trasplante de Órganos , Masculino , Humanos , Anciano , Infecciones por Astroviridae/diagnóstico , Infecciones por Astroviridae/epidemiología , Trasplante de Hígado/efectos adversos , Diarrea , Enteritis/diagnóstico , Enteritis/tratamiento farmacológicoRESUMEN
BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease. RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of these cells acquires a pro-inflammatory transcription and chromatin accessibility profile associated with expression of HAVCR1, VCAM1, and PROM1. These injured epithelial cells have the greatest proportion of LOY and their presence predicts future kidney function decline. Moreover, proximal tubule cells with LOY are more likely to harbor additional large chromosomal gains and express pro-survival pathways. Spatial transcriptomics localizes injured proximal tubule cells to a pro-fibrotic microenvironment where they adopt a secretory phenotype and likely communicate with infiltrating immune cells. CONCLUSIONS: We hypothesize that LOY is an indicator of increased DNA damage and potential marker of cellular senescence that can be applied to single-cell datasets in other tissues.
Asunto(s)
Cromosomas Humanos Y , Insuficiencia Renal Crónica , Humanos , Masculino , Mosaicismo , Envejecimiento/genética , Fenotipo , Insuficiencia Renal Crónica/genéticaRESUMEN
Machine learning has emerged as a significant tool to augment the medical decision-making process. Studies have steadily accrued detailing algorithms and models designed using machine learning to predict and anticipate pathologic states. The cardiac intensive care unit is an area where anticipation is crucial in the division between life and death. In this paper, we aim to review important studies describing the utility of machine learning algorithms to describe the future of artificial intelligence in the cardiac intensive care unit, especially in regards to the prediction of successful ventilatory weaning, acute respiratory distress syndrome, arrhythmia, and acute kidney injury.
Asunto(s)
Inteligencia Artificial , Aprendizaje Automático , Humanos , Unidades de Cuidados Intensivos , Algoritmos , Arritmias CardíacasRESUMEN
Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5371 GLOM and 9787 TUBE genes with at least one variant significantly associated with expression (eGene) by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an "integrative prior" for Bayesian statistical fine-mapping. The use of an integrative prior resulted in higher resolution eQTLs illustrated by (1) smaller numbers of variants in credible sets with greater confidence, (2) increased enrichment of partitioned heritability for GWAS of two kidney traits, (3) an increased number of variants colocalized with the GWAS loci, and (4) enrichment of computationally predicted functional regulatory variants. A subset of variants and genes were validated experimentally in vitro and using a Drosophila nephrocyte model. More broadly, this study demonstrates that tissue-specific eQTL maps informed by single-nucleus open chromatin data have enhanced utility for diverse downstream analyses.
Asunto(s)
Estudio de Asociación del Genoma Completo , Enfermedades Renales , Humanos , Estudio de Asociación del Genoma Completo/métodos , Teorema de Bayes , Enfermedades Renales/genética , Genómica , Cromatina/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad/genéticaRESUMEN
Chromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we developed a sequence-based machine learning method to evaluate and refine chromatin accessibility data. Our framework, gapped k-mer SVM quality check (gkmQC), provides the quality metrics for a sample based on the prediction accuracy of the trained models. We tested 886 DNase-seq samples from the ENCODE/Roadmap projects to demonstrate that gkmQC can effectively identify "high-quality" (HQ) samples with low conventional quality scores owing to marginal read depths. Peaks identified in HQ samples are more accurately aligned at functional regulatory elements, show greater enrichment of regulatory elements harboring functional variants, and explain greater heritability of phenotypes from their relevant tissues. Moreover, gkmQC can optimize the peak-calling threshold to identify additional peaks, especially for rare cell types in single-cell chromatin accessibility data.
Asunto(s)
Cromatina , Secuencias Reguladoras de Ácidos Nucleicos , Cromatina/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Análisis de Secuencia de ADN/métodos , Regulación de la Expresión Génica , GenomaRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor binding motif availability for NF-κB, TEAD, CREB and retinoic acid receptors. We identify and validate a distal enhancer regulating GPRC5A expression containing these motifs. This single cell multiomic analysis of human ADPKD reveals previously unrecognized cellular heterogeneity and provides a foundation to develop better diagnostic and therapeutic approaches.
Asunto(s)
Quistes , Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/metabolismo , Análisis de la Célula Individual , Riñón/metabolismo , Túbulos Renales/metabolismo , Células Epiteliales/metabolismo , Quistes/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess has long been known to increase risk for type 2 diabetes, which raises the possibility that glucocorticoid receptor inhibition may mitigate the adverse metabolic effects of diabetic kidney disease.
Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Cromatina/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Antecedentes Genéticos , Glucosa/metabolismo , Humanos , Receptores de Glucocorticoides/genéticaRESUMEN
Circulating proteins associated with transforming growth factor-ß (TGF-ß) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which of these proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESKD) in humans. Using the SOMAscan proteomic platform, we measured concentrations of 25 TGF-ß signaling family proteins in four different cohorts composed in total of 754 Caucasian or Pima Indian individuals with type 1 or type 2 diabetes. Of these 25 circulating proteins, we identified neuroblastoma suppressor of tumorigenicity 1 (NBL1, aliases DAN and DAND1), a small secreted protein known to inhibit members of the bone morphogenic protein family, to be most strongly and independently associated with progression to ESKD during 10-year follow-up in all cohorts. The extent of damage to podocytes and other glomerular structures measured morphometrically in 105 research kidney biopsies correlated strongly with circulating NBL1 concentrations. Also, in vitro exposure to NBL1 induced apoptosis in podocytes. In conclusion, circulating NBL1 may be involved in the disease process underlying progression to ESKD, and its concentration in circulation may identify subjects with diabetes at increased risk of progression to ESKD.
Asunto(s)
Proteínas de Ciclo Celular/sangre , Diabetes Mellitus Tipo 2 , Fallo Renal Crónico , Neuroblastoma , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Humanos , Proteómica , Factor de Crecimiento Transformador betaRESUMEN
CONTEXT.: Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). The advent of digital pathology and artificial intelligence (AI) have increased interest in virtual microscopy using digital whole slide imaging (WSI) more broadly. OBJECTIVE.: To compare concordance in breast carcinoma grading between AI and a multi-institutional group of breast pathologists using digital WSI. DESIGN.: We have developed an automated NGS framework using deep learning. Six pathologists and AI independently reviewed a digitally scanned slide from 137 invasive carcinomas and assigned a grade based on scoring of the TF, NP, and MC. RESULTS.: Interobserver agreement for the pathologists and AI for overall grade was moderate (κ = 0.471). Agreement was good (κ = 0.681), moderate (κ = 0.442), and fair (κ = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good (κ = 0.313-0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF (κ = 0.471 each) followed by NP (κ = 0.342) and was worst for MC (κ = 0.233). There were no observed differences in concordance amongst pathologists alone versus pathologists + AI. CONCLUSIONS.: Ours is the first study comparing concordance in breast carcinoma grading between a multi-institutional group of pathologists using virtual microscopy to a newly developed WSI AI methodology. Using explainable methods, AI demonstrated similar concordance to pathologists alone.
Asunto(s)
Neoplasias de la Mama , Patólogos , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Inteligencia Artificial , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND AND OBJECTIVES: Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death. RESULTS: After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3). CONCLUSION: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3.
Asunto(s)
Enfermedades Renales/sangre , Adulto , Anciano , Biomarcadores/sangre , Biopsia , Femenino , Humanos , Enfermedades Renales/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Single-cell sequencing technologies have advanced our understanding of kidney biology and disease, but the loss of spatial information in these datasets hinders our interpretation of intercellular communication networks and regional gene expression patterns. New spatial transcriptomic sequencing platforms make it possible to measure the topography of gene expression at genome depth. METHODS: We optimized and validated a female bilateral ischemia-reperfusion injury model. Using the 10× Genomics Visium Spatial Gene Expression solution, we generated spatial maps of gene expression across the injury and repair time course, and applied two open-source computational tools, Giotto and SPOTlight, to increase resolution and measure cell-cell interaction dynamics. RESULTS: An ischemia time of 34 minutes in a female murine model resulted in comparable injury to 22 minutes for males. We report a total of 16,856 unique genes mapped across our injury and repair time course. Giotto, a computational toolbox for spatial data analysis, enabled increased resolution mapping of genes and cell types. Using a seeded nonnegative matrix regression (SPOTlight) to deconvolute the dynamic landscape of cell-cell interactions, we found that injured proximal tubule cells were characterized by increasing macrophage and lymphocyte interactions even 6 weeks after injury, potentially reflecting the AKI to CKD transition. CONCLUSIONS: In this transcriptomic atlas, we defined region-specific and injury-induced loss of differentiation markers and their re-expression during repair, as well as region-specific injury and repair transcriptional responses. Lastly, we created an interactive data visualization application for the scientific community to explore these results (http://humphreyslab.com/SingleCell/).
Asunto(s)
Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Lesión Renal Aguda/fisiopatología , Animales , Comunicación Celular/genética , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica/métodos , Perfilación de la Expresión Génica/estadística & datos numéricos , Ratones , Ratones Endogámicos C57BL , RNA-Seq , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/estadística & datos numéricos , Programas InformáticosRESUMEN
The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
Asunto(s)
Cromatina/genética , Heterogeneidad Genética , Riñón/metabolismo , Transcriptoma , Adulto , Regulación de la Expresión Génica , Factor Nuclear 4 del Hepatocito , Humanos , Persona de Mediana Edad , FN-kappa B , Regiones Promotoras Genéticas , ARN Nuclear Pequeño , Factor de Transcripción AP-2 , Factores de Transcripción/metabolismo , Transposasas , Molécula 1 de Adhesión Celular VascularRESUMEN
Importance: A chronic shortage of donor kidneys is compounded by a high discard rate, and this rate is directly associated with biopsy specimen evaluation, which shows poor reproducibility among pathologists. A deep learning algorithm for measuring percent global glomerulosclerosis (an important predictor of outcome) on images of kidney biopsy specimens could enable pathologists to more reproducibly and accurately quantify percent global glomerulosclerosis, potentially saving organs that would have been discarded. Objective: To compare the performances of pathologists with a deep learning model on quantification of percent global glomerulosclerosis in whole-slide images of donor kidney biopsy specimens, and to determine the potential benefit of a deep learning model on organ discard rates. Design, Setting, and Participants: This prognostic study used whole-slide images acquired from 98 hematoxylin-eosin-stained frozen and 51 permanent donor biopsy specimen sections retrieved from 83 kidneys. Serial annotation by 3 board-certified pathologists served as ground truth for model training and for evaluation. Images of kidney biopsy specimens were obtained from the Washington University database (retrieved between June 2015 and June 2017). Cases were selected randomly from a database of more than 1000 cases to include biopsy specimens representing an equitable distribution within 0% to 5%, 6% to 10%, 11% to 15%, 16% to 20%, and more than 20% global glomerulosclerosis. Main Outcomes and Measures: Correlation coefficient (r) and root-mean-square error (RMSE) with respect to annotations were computed for cross-validated model predictions and on-call pathologists' estimates of percent global glomerulosclerosis when using individual and pooled slide results. Data were analyzed from March 2018 to August 2020. Results: The cross-validated model results of section images retrieved from 83 donor kidneys showed higher correlation with annotations (r = 0.916; 95% CI, 0.886-0.939) than on-call pathologists (r = 0.884; 95% CI, 0.825-0.923) that was enhanced when pooling glomeruli counts from multiple levels (r = 0.933; 95% CI, 0.898-0.956). Model prediction error for single levels (RMSE, 5.631; 95% CI, 4.735-6.517) was 14% lower than on-call pathologists (RMSE, 6.523; 95% CI, 5.191-7.783), improving to 22% with multiple levels (RMSE, 5.094; 95% CI, 3.972-6.301). The model decreased the likelihood of unnecessary organ discard by 37% compared with pathologists. Conclusions and Relevance: The findings of this prognostic study suggest that this deep learning model provided a scalable and robust method to quantify percent global glomerulosclerosis in whole-slide images of donor kidneys. The model performance improved by analyzing multiple levels of a section, surpassing the capacity of pathologists in the time-sensitive setting of examining donor biopsy specimens. The results indicate the potential of a deep learning model to prevent erroneous donor organ discard.