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1. Advancing mouse models for transplantation research

Author

Cravedi, Paolo, Riella, Leonardo V., Ford, Mandy L., Valujskikh, Anna, Menon, Madhav C., Kirk, Allan D., Alegre, Maria-Luisa, Alessandrini, Alessandro, Feng, Sandy, Kehn, Patricia, Najafian, Nader, Hancock, Wayne W., Heeger, Peter S., Maltzman, Jonathan S., Mannon, Roslyn B., Nadig, Satish N., Odim, Jonah, Turnquist, Heth, Shaw, Julia, West, Lori, Luo, Xunrong, Chong, Anita S., and Bromberg, Jonathan S.

Published
2024
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2. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis

Author

Barsotti, Gabriel C., Luciano, Randy, Kumar, Ashwani, Meliambro, Kristin, Kakade, Vijayakumar, Tokita, Joji, Naik, Abhijit, Fu, Jia, Peck, Elizabeth, Pell, John, Reghuvaran, Anand, Tanvir, E.M., Patel, Prashant, Zhang, Weijia, Li, Fan, Moeckel, Gilbert, Perincheri, Sudhir, Cantley, Lloyd, Moledina, Dennis G., Wilson, F. Perry, He, John C., and Menon, Madhav C.

Published
2024
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4. A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization

Author

Yi, Zhengzi, Xi, Caixia, Menon, Madhav C., Cravedi, Paolo, Tedla, Fasika, Soto, Alan, Sun, Zeguo, Liu, Keyu, Zhang, Jason, Wei, Chengguo, Chen, Man, Wang, Wenlin, Veremis, Brandon, Garcia-barros, Monica, Kumar, Abhishek, Haakinson, Danielle, Brody, Rachel, Azeloglu, Evren U., Gallon, Lorenzo, O’Connell, Philip, Naesens, Maarten, Shapiro, Ron, Colvin, Robert B., Ward, Stephen, Salem, Fadi, and Zhang, Weijia

Published
2024
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5. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant

Author

Murakami, Naoka, Mulvaney, Patrick, Danesh, Melissa, Abudayyeh, Ala, Diab, Adi, Abdel-Wahab, Noha, Abdelrahim, Maen, Khairallah, Pascale, Shirazian, Shayan, Kukla, Aleksandra, Owoyemi, Itunu O, Alhamad, Tarek, Husami, Samir, Menon, Madhav, Santeusanio, Andrew, Blosser, Christopher D, Zuniga, Sandra Carias, Soler, Maria Jose, Moreso, Francesc, Mithani, Zain, Ortiz-Melo, David, Jaimes, Edgar A, Gutgarts, Victoria, Lum, Erik, Danovitch, Gabriel M, Cardarelli, Francesca, Drews, Reed E, Bassil, Claude, Swank, Jennifer L, Westphal, Scott, Mannon, Roslyn B, Shirai, Keisuke, Kitchlu, Abhijat, Ong, Song, Machado, Shana M, Mothi, Suraj S, Ott, Patrick A, Rahma, Osama, Hodi, F Stephen, Sise, Meghan E, Gupta, Shruti, Leaf, David E, Devoe, Craig E, Wanchoo, Rimda, Nair, Vinay V, Schmults, Chrysalyne D, Hanna, Glenn J, Sprangers, Ben, Riella, Leonardo V, Jhaveri, Kenar D, and Consortium, Immune Checkpoint Inhibitors in Solid Organ Transplant

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Organ Transplantation, Kidney Disease, Transplantation, Cancer, Rare Diseases, Clinical Research, Prevention, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Renal and urogenital, Carcinoma, Squamous Cell, Humans, Immune Checkpoint Inhibitors, Kidney Transplantation, Prospective Studies, Retrospective Studies, Skin Neoplasms, immune checkpoint inhibitors, kidney transplant, onconephrology, rejection, Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium, Urology & Nephrology, Clinical sciences
Abstract

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Published
2021

6. First randomised controlled trial comparing the sirolimus-eluting bioadaptor with the zotarolimus-eluting drug-eluting stent in patients with de novo coronary artery lesions: 12-month clinical and imaging data from the multi-centre, international, BIODAPTOR-RCT

Author

Saito, Shigeru, Bennett, Johan, Nef, Holger M., Webster, Mark, Namiki, Atsuo, Takahashi, Akihiko, Kakuta, Tsunekazu, Yamazaki, Seiji, Shibata, Yoshisato, Scott, Douglas, Vrolix, Mathias, Menon, Madhav, Möllmann, Helge, Werner, Nikos, Neylon, Antoinette, Mehmedbegovic, Zlatko, Smits, Pieter C., Morice, Marie-Claude, and Verheye, Stefan

Published
2023
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7. APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale

Author

Freedman, Barry I, Moxey-Mims, Marva M, Alexander, Amir A, Astor, Brad C, Birdwell, Kelly A, Bowden, Donald W, Bowen, Gordon, Bromberg, Jonathan, Craven, Timothy E, Dadhania, Darshana M, Divers, Jasmin, Doshi, Mona D, Eidbo, Elling, Fornoni, Alessia, Gautreaux, Michael D, Gbadegesin, Rasheed A, Gee, Patrick O, Guerra, Giselle, Hsu, Chi-yuan, Iltis, Ana S, Jefferson, Nichole, Julian, Bruce A, Klassen, David K, Koty, Patrick P, Langefeld, Carl D, Lentine, Krista L, Ma, Lijun, Mannon, Roslyn B, Menon, Madhav C, Mohan, Sumit, Moore, J Brian, Murphy, Barbara, Newell, Kenneth A, Odim, Jonah, Ortigosa-Goggins, Mariella, Palmer, Nicholette D, Park, Meyeon, Parsa, Afshin, Pastan, Stephen O, Poggio, Emilio D, Rajapakse, Nishadi, Reeves-Daniel, Amber M, Rosas, Sylvia E, Russell, Laurie P, Sawinski, Deirdre, Smith, S Carrie, Spainhour, Mitzie, Stratta, Robert J, Weir, Matthew R, Reboussin, David M, Kimmel, Paul L, and Brennan, Daniel C

Subjects
Clinical Research, Organ Transplantation, Transplantation, Kidney Disease, Renal and urogenital, Good Health and Well Being, African Americans, APOL1, chronic kidney disease, graft failure, kidney transplantation, outcomes
Abstract

IntroductionMuch of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes.MethodsAPOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.ResultsThe United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.ConclusionThis article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Published
2020

8. Profilin1 is required for prevention of mitotic catastrophe in murine and human glomerular diseases

Author

Tian, Xuefei, Pedigo, Christopher E., Li, Ke, Ma, Xiaotao, Bunda, Patricia, Pell, John, Lek, Angela, Gu, Jianlei, Zhang, Yan, Rangel, Paulina X. Medina, Li, Wei, Schwartze, Eike, Nagata, Soichiro, Lerner, Gabriel, Perincheri, Sudhir, Priyadarshini, Anupama, Zhao, Hongyu, Lek, Monkol, Menon, Madhav C., Fu, Rongguo, and Ishibe, Shuta

Subjects
Physiological aspects, Development and progression, Health aspects, Mitosis -- Health aspects -- Physiological aspects, Glomerulonephritis -- Development and progression, Epithelial cells -- Physiological aspects -- Health aspects, Binding proteins -- Physiological aspects -- Health aspects
Abstract

Introduction Podocytes are specialized terminally differentiated epithelial cells that line the kidney filtration barrier. Unlike typical epithelial cells that are compressed against their basement membrane, podocytes are situated on the [...], The progression of proteinuric kidney diseases is associated with podocyte loss, but the mechanisms underlying this process remain unclear. Podocytes reenter the cell cycle to repair double-stranded DNA breaks. However, unsuccessful repair can result in podocytes crossing the [G.sub.1]/S checkpoint and undergoing abortive cytokinesis. In this study, we identified Pfn1 as indispensable in maintaining glomerular integrity--its tissue-specific loss in mouse podocytes resulted in severe proteinuria and kidney failure. Our results suggest that this phenotype is due to podocyte mitotic catastrophe (MC), characterized histologically and ultrastructurally by abundant multinucleated cells, irregular nuclei, and mitotic spindles. Podocyte cell cycle reentry was identified using FUCCI2aR mice, and we observed altered expression of cellcycle associated proteins, such as p21, p53, cyclin B1, and cyclin D1. Podocyte-specific translating ribosome affinity purification and RNA-Seq revealed the downregulation of ribosomal RNA-processing 8 (Rrp8). Overexpression of Rrp8 in Pfn1-KO podocytes partially rescued the phenotype in vitro. Clinical and ultrastructural tomographic analysis of patients with diverse proteinuric kidney diseases further validated the presence of MC podocytes and reduction in podocyte PFN1 expression within kidney tissues. These results suggest that profilinl is essential in regulating the podocyte cell cycle and its disruption leads to MC and subsequent podocyte loss.

Published
2023
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9. Cellular recovery after prolonged warm ischaemia of the whole body

Author

Andrijevic, David, Vrselja, Zvonimir, Lysyy, Taras, Zhang, Shupei, Skarica, Mario, Spajic, Ana, Dellal, David, Thorn, Stephanie L., Duckrow, Robert B., Ma, Shaojie, Duy, Phan Q., Isiktas, Atagun U., Liang, Dan, Li, Mingfeng, Kim, Suel-Kee, Daniele, Stefano G., Banu, Khadija, Perincheri, Sudhir, Menon, Madhav C., Huttner, Anita, Sheth, Kevin N., Gobeske, Kevin T., Tietjen, Gregory T., Zaveri, Hitten P., Latham, Stephen R., Sinusas, Albert J., and Sestan, Nenad

Published
2022
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10. Re-Evaluating the Transplant Glomerulopathy Lesion—Beyond Donor-Specific Antibodies.

Author

Chutani, Arun, Guevara-Pineda, Daniel, Lerner, Gabriel B., and Menon, Madhav C.

Subjects
KIDNEY transplantation, GRAFT survival, HOMOGRAFTS, DIAGNOSIS, IMMUNOGLOBULINS
Abstract

There have been significant advances in short-term outcomes in renal transplantation. However, longer-term graft survival has improved only minimally. After the first post-transplant year, it has been estimated that chronic allograft damage is responsible for 5% of graft loss per year. Transplant glomerulopathy (TG), a unique morphologic lesion, is reported to accompany progressive chronic allograft dysfunction in many cases. While not constituting a specific etiologic diagnosis, TG is primarily considered as a histologic manifestation of ongoing allo-immune damage from donor-specific anti-HLA alloantibodies (DSA). In this review article, we re-evaluate the existing literature on TG, with particular emphasis on the role of non-HLA-antibodies and complement-mediated injury, cell-mediated immune mechanisms, and early podocyte stress in the pathogenesis of Transplant Glomerulopathy. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival

Author

Sun, Zeguo, Zhang, Zhongyang, Banu, Khadija, Gibson, Ian W., Colvin, Robert B., Yi, Zhengzi, Zhang, Weijia, De Kumar, Bony, Reghuvaran, Anand, Pell, John, Manes, Thomas D., Djamali, Arjang, Gallon, Lorenzo, O'Connell, Philip J., He, John Cijiang, Pober, Jordan S., Heeger, Peter S., and Menon, Madhav C.

Subjects
Complications and side effects, Genetic aspects, Health aspects, Kidney transplantation -- Complications and side effects, HLA antigens -- Genetic aspects -- Health aspects, Graft rejection -- Genetic aspects, DNA mismatch repair -- Health aspects, Kidneys -- Transplantation, HLA histocompatibility antigens -- Genetic aspects -- Health aspects, Histocompatibility antigens -- Genetic aspects -- Health aspects
Abstract

Introduction In renal transplantation, short-term allograft outcomes, including acute rejection, have significantly improved, without a proportionate improvement in long-term allograft outcomes (1). While distinct etiologies are identifiable in half of [...], Donor-recipient (D-R) mismatches outside of human leukocyte antigens (HLAs) contribute to kidney allograft loss, but the mechanisms remain unclear, specifically for intronic mismatches. We quantified non-HLA mismatches at variant-, gene-, and genome-wide scales from single nucleotide polymorphism (SNP) data of D-Rs from 2 well-phenotyped transplant cohorts: Genomics of Chronic Allograft Rejection (GoCAR; n = 385) and Clinical Trials in Organ Transplantation-01/17 (CTOT-01/17; n = 146). Unbiased gene-level screening in GoCAR uncovered the LIMS1 locus as the top-ranked gene where D-R mismatches associated with death-censored graft loss (DCGL). A previously unreported, intronic, LIMS1 haplotype of 30 SNPs independently associated with DCGL in both cohorts. Haplotype mismatches showed a dosage effect, and minor-allele introduction to major-allele-carrying recipients showed greater hazard of DCGL. The LIMS1 haplotype and the previously reported LIMS1 SNP rs893403 are expression quantitative trait loci (eQTL) in immune cells for GCC2 (not LIMS1), which encodes a protein involved in mannose-6-phosphase receptor (M6PR) recycling. Peripheral blood and T cell transcriptome analyses associated the GCC2 gene and LIMS1 SNPs with the TGF-[beta]1/SMAD pathway, suggesting a regulatory effect. In vitro GCC2 modulation impacted M6PRdependent regulation of active TGF-[beta]1 and downstream signaling in T cells. Together, our data link LIMS1 locus D-R mismatches to DCGL via GCC2 eQTLs that modulate TGF-[beta]1-dependent effects on T cells.

Published
2023
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12. Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies

Author

Yi, Zhengzi, Salem, Fadi, Menon, Madhav C., Keung, Karen, Xi, Caixia, Hultin, Sebastian, Haroon Al Rasheed, M. Rizwan, Li, Li, Su, Fei, Sun, Zeguo, Wei, Chengguo, Huang, Weiqing, Fredericks, Samuel, Lin, Qisheng, Banu, Khadija, Wong, Germaine, Rogers, Natasha M., Farouk, Samira, Cravedi, Paolo, Shingde, Meena, Smith, R. Neal, Rosales, Ivy A., O’Connell, Philip J., Colvin, Robert B., Murphy, Barbara, and Zhang, Weijia

Published
2022
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15. Temporal trends of dialysis requiring acute kidney injury after orthotopic cardiac and liver transplant hospitalizations

Author

Nadkarni, Girish N, Chauhan, Kinsuk, Patel, Achint, Saha, Aparna, Poojary, Priti, Kamat, Sunil, Patel, Shanti, Ferrandino, Rocco, Konstantinidis, Ioannis, Garimella, Pranav S, Menon, Madhav C, and Thakar, Charuhas V

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Organ Transplantation, Digestive Diseases, Clinical Research, Transplantation, Kidney Disease, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Renal and urogenital, Good Health and Well Being, Acute Kidney Injury, Adolescent, Adult, Aged, Cohort Studies, Female, Heart Transplantation, Hospitalization, Humans, Liver Transplantation, Male, Middle Aged, Renal Dialysis, Retrospective Studies, Time Factors, Young Adult, Acute kidney injury, Cardiac transplant, Liver transplant, Mortality, Outcomes, Urology & Nephrology, Clinical sciences, Health services and systems, Nursing
Abstract

BackgroundThe epidemiology and outcomes of acute kidney injury (AKI) in prevalent non-renal solid organ transplant recipients is unknown.MethodsWe assessed the epidemiology of trends in acute kidney injury (AKI) in orthotopic cardiac and liver transplant recipients in the United States. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends (2002 to 2013) of the primary outcome, defined as AKI requiring dialysis (AKI-D) in hospitalizations after cardiac and liver transplantation. We also evaluated the trend and impact of AKI-D on hospital mortality and adverse discharge using adjusted odds ratios (aOR).ResultsThe proportion of hospitalizations with AKI (9.7 to 32.7% in cardiac and 8.5 to 28.1% in liver transplant hospitalizations; ptrend

Published
2017

16. Stratified Abstraction of Access Control Policies

Author

Backes, John, Berrueco, Ulises, Bray, Tyler, Brim, Daniel, Cook, Byron, Gacek, Andrew, Jhala, Ranjit, Luckow, Kasper, McLaughlin, Sean, Menon, Madhav, Peebles, Daniel, Pugalia, Ujjwal, Rungta, Neha, Schlesinger, Cole, Schodde, Adam, Tanuku, Anvesh, Varming, Carsten, Viswanathan, Deepa, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Lahiri, Shuvendu K., editor, and Wang, Chao, editor

Published
2020
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17. Percutaneous Coronary Intervention Using the DynamX Sirolimus‐Eluting Bioadaptor: 12‐Month Clinical and Imaging Outcomes.

Author

Webster, Mark, Scott, Douglas, Menon, Madhav, McClean, Dougal, El-Jack, Seif, Wilkins, Gerard, Harding, Scott A., and Nguyen, Thach N.

Subjects
INTRAVASCULAR ultrasonography, PERCUTANEOUS coronary intervention, OPTICAL coherence tomography, MYOCARDIAL infarction, DRUG-eluting stents, DIAGNOSTIC imaging
Abstract

The DynamX Bioadaptor is a novel implant with uncaging elements that disengage after polymer resorption and permits restoration of vessel function, thereby potentially reducing late adverse cardiac events. We evaluated the safety and efficacy of this novel implant with imaging follow‐up at 6‐months, the time point when the bioadaptor starts to uncage. This prospective study enrolled 44 patients with up to two de novo lesions at seven centers in New Zealand treated with the DynamX Bioadaptor. Follow‐up was planned out to 12‐months. The primary safety and efficacy endpoints were 6‐month target lesion failure (TLF) and late lumen loss. Patients presented with non‐ST elevation myocardial infarction in 49%. Lesions (n = 45) were 16.0 ± 6.7 mm long, and 2.81 ± 0.41 mm in diameter. Device and procedure success were 100%, and acute lumen gain was 1.93 ± 0.35 mm. At 6‐months, median in‐device late lumen loss was 0.09 mm (IQR:0.05–0.16). Measured by intravascular ultrasound, the vessel, lumen, and device area remained constant. By optical coherence tomography, 96.4% ± 5.9% of struts per lesion were covered. Out to 12‐months, no TLF and no definite or probable device thrombosis were reported. In conclusion, this study provides evidence of the safety and performance of the DynamX Bioadaptor with excellent 12‐month clinical and 6‐month imaging outcomes comparable to best‐in‐class drug‐eluting stents (DES). Trial Registration: ClinicalTrials.gov identifier: NCT03634020, NCT05464147, NCT04562805, and NCT04192747. [ABSTRACT FROM AUTHOR]

Published
2024
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21. FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction

Author

Böhm, Felix, Mogensen, Brynjölfur, Engstrøm, Thomas, Stankovic, Goran, Srdanovic, Ilija, Lønborg, Jacob, Zwackman, Sammy, Hamid, Mehmet, Kellerth, Thomas, Lauermann, Jörg, Kajander, Olli A., Andersson, Jonas, Linder, Rikard, Angerås, Oskar, Renlund, Henrik, Ērglis, Andrejs, Menon, Madhav, Schultz, Carl, Laine, Mika, Held, Claes, Rück, Andreas, Östlund, Ollie, James, Stefan, Böhm, Felix, Mogensen, Brynjölfur, Engstrøm, Thomas, Stankovic, Goran, Srdanovic, Ilija, Lønborg, Jacob, Zwackman, Sammy, Hamid, Mehmet, Kellerth, Thomas, Lauermann, Jörg, Kajander, Olli A., Andersson, Jonas, Linder, Rikard, Angerås, Oskar, Renlund, Henrik, Ērglis, Andrejs, Menon, Madhav, Schultz, Carl, Laine, Mika, Held, Claes, Rück, Andreas, Östlund, Ollie, and James, Stefan

Abstract

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Re, QC 20240521

Published
2024
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23. Genetic polymorphisms of Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3) gene in African American kidney transplant recipients are associated with post-transplant graft failure

Author

Sun, Zeguo, primary, Yi, Zhengzi, additional, Wei, Chengguo, additional, Wang, Wenlin, additional, Cravedi, Paolo, additional, Tedla, Fasika, additional, Ward, Stephen C., additional, Azeloglu, Evren, additional, Schrider, Daniel R., additional, Li, Yun, additional, Ali, Sumaria, additional, Ren, Tianyuan, additional, Liu, Shun, additional, Liang, Deguang, additional, Fu, Jia, additional, Liu, Tong, additional, Li, Hong, additional, Xi, Caixia, additional, Vy, Thi Ha, additional, Mosoyan, Gohar, additional, Sun, Quan, additional, Kumar, Ashwani, additional, Zhang, Zhongyang, additional, Farouk, Samira, additional, Campell, Kirk, additional, Ochando, Jordi, additional, Lee, Kyung, additional, Coca, Steve, additional, Xiang, Jenny, additional, Connolly, Patti, additional, Gallon, Lorenzo, additional, Colvin, Robert, additional, Menon, Madhav, additional, Nadkarni, Girish, additional, He, John C., additional, Kraft, Monica, additional, Jiang, Xuejun, additional, Zhang, Xuewu, additional, Zhang, Weiguo, additional, Chen, Shu-hsia, additional, Heeger, Peter, additional, and Zhang, Weijia, additional

Published
2024
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24. Rationale and Design of a of a Phase 2, Double-blind, Placebo-controlled, Randomized Trial Evaluating AMPK-activation by Metformin in Focal Segmental Glomerulosclerosis

Author

Barsotti, Gabriel C., primary, Luciano, Randy, additional, Kumar, Ashwani, additional, Meliambro, Kristin, additional, Kakade, Vijayakumar, additional, Tokita, Joji, additional, Naik, Abhijit, additional, Fu, Jia, additional, Peck, Elizabeth, additional, Pell, John, additional, Reghuvaran, Anand, additional, Tanvir, E.M., additional, Patel, Prashant, additional, Zhang, Weijia, additional, Li, Fan, additional, Moeckel, Gilbert, additional, Perincheri, Sudhir, additional, Cantley, Lloyd, additional, Moledina, Dennis G., additional, Perry-Wilson, F., additional, He, John C., additional, and Menon, Madhav C., additional

Published
2024
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30. A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization

Author

Yi, Zhengzi, primary, Xi, Caixia, additional, Menon, Madhav C., additional, Cravedi, Paolo, additional, Tedla, Fasika, additional, Soto, Alan, additional, Sun, Zeguo, additional, Liu, Keyu, additional, Zhang, Jason, additional, Wei, Chengguo, additional, Chen, Man, additional, Wang, Wenlin, additional, Veremis, Brandon, additional, Garcia-barros, Monica, additional, Kumar, Abhishek, additional, Haakinson, Danielle, additional, Brody, Rachel, additional, Azeloglu, Evren U., additional, Gallon, Lorenzo, additional, O’Connell, Philip, additional, Naesens, Maarten, additional, Shapiro, Ron, additional, Colvin, Robert B., additional, Ward, Stephen, additional, Salem, Fadi, additional, and Zhang, Weijia, additional

Published
2023
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31. Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases

Author

Tian, Xuefei, primary, Pedigo, Christopher E., additional, Li, Ke, additional, Ma, Xiaotao, additional, Bunda, Patricia, additional, Pell, John, additional, Lek, Angela, additional, Gu, Jianlei, additional, Zhang, Yan, additional, Medina Rangel, Paulina X., additional, Li, Wei, additional, Schwartze, Eike, additional, Nagata, Soichiro, additional, Lerner, Gabriel, additional, Perincheri, Sudhir, additional, Priyadarshini, Anupama, additional, Zhao, Hongyu, additional, Lek, Monkol, additional, Menon, Madhav C., additional, Fu, Rongguo, additional, and Ishibe, Shuta, additional

Published
2023
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32. Stratified Abstraction of Access Control Policies

Author

Backes, John, primary, Berrueco, Ulises, additional, Bray, Tyler, additional, Brim, Daniel, additional, Cook, Byron, additional, Gacek, Andrew, additional, Jhala, Ranjit, additional, Luckow, Kasper, additional, McLaughlin, Sean, additional, Menon, Madhav, additional, Peebles, Daniel, additional, Pugalia, Ujjwal, additional, Rungta, Neha, additional, Schlesinger, Cole, additional, Schodde, Adam, additional, Tanuku, Anvesh, additional, Varming, Carsten, additional, and Viswanathan, Deepa, additional

Published
2020
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33. Contributors

Author

Agarwal, Gaurav, primary, Al-Qaoud, Talal M., additional, Alexander, Barbara D., additional, Allen, Richard D.M., additional, Ambagtsheer, Frederike, additional, Barth, Rolf N., additional, Basu, Amit, additional, Castro-Dopico, Tomas, additional, Chambers, Eileen T., additional, Chapman, Jeremy R., additional, R. Clatworthy, Menna, additional, Collins, Bradley Henry, additional, Colvin, Robert B., additional, Cornell, Lynn D., additional, Costa, Sylvia F., additional, Crane, Alice, additional, Davenport, Andrew, additional, Ellis, Matthew J., additional, Ezekian, Brian, additional, Farin, Casey Victoria, additional, Farris, Alton B., additional, Fishman, Jay A., additional, Florman, MD, Sander, additional, Forsythe, John L.R., additional, J. Friend, Peter, additional, V. Fuggle, Susan, additional, Garro, Rouba, additional, Gaston, Robert S., additional, Geissler, Edward K., additional, Gentry, Sommer Elizabeth, additional, A. Gilbert, James, additional, Hamilton, David, additional, E. Hamoda, Reem, additional, Hoffman, Benson M., additional, Holzner, Matthew L., additional, Hooten, Joanna, additional, Hunter, James P., additional, Jardine, Alan G., additional, S. Johnson, Laura, additional, A. Kahokehr, Arman, additional, Kaufman, Dixon B., additional, Keung, Karen L., additional, Kirk, Allan D., additional, Knechtle, Stuart J., additional, Knight, Simon R., additional, Kronish, Kate, additional, LaMattina, John C., additional, Lees, Jennifer S., additional, Leuvenink, Henri, additional, Locke, Jayme E., additional, Lucey, Michael R., additional, Luedke, Matthew William, additional, Marano, Anne Louise, additional, Marson, Lorna P., additional, Mathieu, Chantal, additional, Menon, Madhav C., additional, Morris, Sir Peter J., additional, Muller, Elmi, additional, Murphy, Barbara, additional, Myers, Sarah A., additional, Nankivell, Brian J., additional, U. Niemann, Claus, additional, O’Callaghan, John, additional, O’Connell, Philip John, additional, S. Odorico, Jon, additional, Olmos, Andrea, additional, Oniscu, Gabriel, additional, Patzer, Rachel E., additional, Pengel, Liset H.M., additional, Peterson, Andrew C., additional, Pirenne, Jacques, additional, Ploeg, Rutger J., additional, Rosales, Brenda Maria, additional, Safdar, MD, Nasia, additional, Said, Adnan, additional, Saulino, Caroline K., additional, Schinstock, Carrie, additional, Schroder, Paul M., additional, Segev, Dorry L., additional, Shapiro, Ron, additional, A. Shoskes, Daniel, additional, Smith, Patrick J., additional, Sprangers, Ben, additional, Stegall, Mark, additional, M. Subramanian, Ram, additional, J. Taylor, Craig, additional, Thompson, John F., additional, Wadhera, Vikram, additional, Waer, Mark, additional, J.E. Watson, Christopher, additional, Webster, Angela Claire, additional, Weimar, Willem, additional, Winterberg, Pamela D., additional, Wood, Kathryn J., additional, and Wu, Diana A., additional

Published
2020
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35. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes

Author

Zhang, Zhongyang, Sun, Zeguo, Fu, Jia, Lin, Qisheng, Banu, Khadija, Chauhan, Kinsuk, Planoutene, Marina, Wei, Chengguo, Salem, Fadi, Yi, Zhengzi, Liu, Ruijie, Cravedi, Paolo, Cheng, Haoxiang, Hao, Ke, O'Connell, Philip J., Ishibe, Shuta, Zhang, Weijia, Coca, Steven G., Gibson, Ian W., Colvin, Robert B., He, John Cijiang, Heeger, Peter S., Murphy, Barbara, and Menon, Madhav C.

Subjects
Complications and side effects, Genetic aspects, Risk factors, Health aspects, Alleles -- Health aspects, Kidney transplantation -- Complications and side effects -- Genetic aspects, Apolipoproteins -- Genetic aspects -- Health aspects, Organ transplant recipients -- Genetic aspects, Graft rejection -- Genetic aspects -- Risk factors, Kidneys -- Transplantation, Allelomorphism -- Health aspects
Abstract

Introduction Patients with African ancestry have a significantly higher risk of non-Mendelian focal segmental glomerulosclerosis (FSGS) as well as end-stage renal disease (ESRD) (reviewed in ref. 1). Seminal work identified [...], Apolipoprotein L1 (APOL1) risk alleles in donor kidneys associate with graft loss, but whether recipient risk allele expression affects transplant outcomes is unclear. To test whether recipient APOL1 risk alleles independently correlate with transplant outcomes, we analyzed genome-wide SNP genotyping data on donors and recipients from 2 kidney transplant cohorts: Genomics of Chronic Allograft Rejection (GOCAR) and Clinical Trials in Organ Transplantation 01/17 (CTOT-01/17). We estimated genetic ancestry (quantified as the proportion of African ancestry, or pAFR) by ADMIXTURE and correlated APOL1 genotypes and pAFR with outcomes. In the GOCAR discovery set, we noted that the number of recipient APOL1 G1/G2 alleles (R-nAPOL1) associated with an increased risk of death-censored allograft loss (DCAL), independent of ancestry (HR = 2.14; P = 0.006), as well as within the subgroup of African American and Hispanic (AA/H) recipients (HR = 2.36; P = 0.003). R-nAPOL1 also associated with an increased risk of any T cell-mediated rejection (TCMR) event. These associations were validated in CTOT-01/17. Ex vivo studies of PMBCs revealed, unexpectedly, high expression levels of APOL1 in activated [CD4.sup.+]/[CD8.sup.+] T cells and NK cells. We detected enriched immune response gene pathways in risk allele carriers compared with noncarriers on the kidney transplant waitlist and among healthy controls. Our findings demonstrate an immunomodulatory role for recipient APOL1 risk alleles associated with TCMR and DCAL. We believe this finding has broader implications for immune-mediated injury to native kidneys.

Published
2021
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37. Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli

Author

Reghuvaran, Anand C., primary, Lin, Qisheng, additional, Basgen, John M., additional, Banu, Khadija, additional, Shi, Hongmei, additional, Vashist, Anushree, additional, Pell, John, additional, Perinchery, Sudhir, additional, He, John C., additional, Moledina, Dennis, additional, Wilson, F. Perry, additional, and Menon, Madhav C., additional

Published
2023
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38. Deep-learning Based Pathological Assessment of Frozen Procurement Kidney Biopsies Predicts Graft Loss and Guides Organ Utilization: A Large-scale Retrospective Study

Author

Yi, Zhengzi, primary, Xi, Caixia, additional, Menon, Madhav C, additional, Cravedi, Paolo, additional, Tedla, Fasika, additional, Soto, Alan, additional, Sun, Zeguo, additional, Liu, Keyu, additional, Zhang, Jason, additional, Wei, Chengguo, additional, Chen, Man, additional, Wang, Wenlin, additional, Veremis, Brandon, additional, Garcia-barros, Monica, additional, Kumar, Abhishek, additional, Haakinson, Danielle, additional, Brody, Rachel, additional, Gallon, Lorenzo, additional, O'Connell, Philip, additional, Naesens, Maarten, additional, Shapiro, Ron, additional, Colvin, Robert, additional, Ward, Stephen, additional, Salem, Fadi, additional, and Zhang, Weijia, additional

Published
2023
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39. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study

Author

O'Connell, Philip J, Zhang, Weijia, Menon, Madhav C, Yi, Zhengzi, Schröppel, Bernd, Gallon, Lorenzo, Luan, Yi, Rosales, Ivy A, Ge, Yongchao, Losic, Bojan, Xi, Caixia, Woytovich, Christopher, Keung, Karen L, Wei, Chengguo, Greene, Ilana, Overbey, Jessica, Bagiella, Emilia, Najafian, Nader, Samaniego, Milagros, Djamali, Arjang, Alexander, Stephen I, Nankivell, Brian J, Chapman, Jeremy R, Smith, Rex Neal, Colvin, Robert, and Murphy, Barbara

Published
2016
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42. Contributors

Author

Albright, Robert C., primary, Amerling, Richard, additional, Angeli, Paolo, additional, Angelotti, Maria Lucia, additional, Antonelli, Massimo, additional, Antoniotti, Riccardo, additional, Arulkumaran, Nishkantha, additional, Asfar, Pierre, additional, Ash, Stephen R., additional, Aucella, Filippo, additional, Aucella, Francesco, additional, Ave, Samuele, additional, Bagshaw, Sean M., additional, Balaraman, Vasanthi, additional, Baldwin, Ian, additional, Bargman, Joanne M., additional, Barletta, Gina-Marie, additional, Barletta, Jeffrey F., additional, Barnela, Shriganesh R., additional, Bayır, Hülya, additional, Beaulieu, Monica, additional, Bellasi, Antonio, additional, Bellomo, Rinaldo, additional, Beloncle, François, additional, Bhansali, Arjun, additional, Bihorac, Azra, additional, Billings, Frederic T., additional, Birk, Horst-Walter, additional, Bonilla-Reséndiz, Luis Ignacio, additional, Bouchard, Josée, additional, Bourke, Edmund, additional, Braitberg, George, additional, Brendolan, Alessandra, additional, Brocca, Alessandra, additional, Brophy, Patrick D., additional, Bucala, Richard, additional, Bunchman, Timothy E., additional, Burdmann, Emmanuel A., additional, Busse, Laurence W., additional, Caires, Renato Antunes, additional, Caironi, Pietro, additional, Camilla, Roberta, additional, Campos, Israel, additional, Canaud, Bernard, additional, Cantaluppi, Vincenzo, additional, Martinez, Maria P., additional, Capasso, Giovambattista, additional, Carcillo, Joseph A., additional, Carlesso, Eleonora, additional, Casino, Francesco G., additional, Castellano, Giuseppe, additional, Catania, Matteo, additional, Cawcutt, Kelly A., additional, Cerda, Jorge, additional, Charen, Elliot, additional, Chawla, Lakhmir S., additional, Chiaramonte, Stefano, additional, Chua, Horng-Ruey, additional, Cianciaruso, Bruno, additional, Ciceri, Paola, additional, Cieslak, Jacek, additional, Clark, William R., additional, Claure-Del Granado, Rolando, additional, Clementi, Anna, additional, Co, Ivan N., additional, Coelho, Fernanda Oliveira, additional, Conte, Ferruccio, additional, Corey, Howard E., additional, Cosmai, Laura, additional, Costalonga, Elerson Carlos, additional, Costamagna, Andrea, additional, Costanzo, Maria Rosa, additional, Cozzolino, Mario, additional, Cramer, Carl H., additional, Cravedi, Paolo, additional, Crepaldi, Carlo, additional, Creteur, Jacques, additional, Crew, R. John, additional, da Costa e Silva, Verônica Torres, additional, Davenport, Andrew, additional, Davies, Andrew R., additional, D'Costa, Rohit, additional, Dean, Dawson F., additional, Debiais, Charlotte, additional, de Cal, Massimo, additional, Dedhia, Paras, additional, de Grooth, Harm-Jan, additional, Dell'Aquila, Roberto, additional, Dellepiane, Sergio, additional, Dellinger, Richard Phillip, additional, Del Vecchio, Lucia, additional, Depner, Thomas A., additional, De Rosa, Silvia, additional, Deutschman, Clifford S., additional, Devarajan, Prasad, additional, Dewitte, A., additional, Di Iorio, Biagio R., additional, Di Lullo, Luca, additional, Di Micco, Lucia, additional, Di Nardo, Matteo, additional, Ding, Xiaoqiang, additional, D'Ippoliti, Fiorella, additional, Di Somma, Salvatore, additional, Doi, Kent, additional, Dries, David J., additional, Druml, Wilfred, additional, Duke, Graeme, additional, Durand, Francois, additional, Eadon, Michael T., additional, Eckstein, Devin, additional, Egi, Moritoki, additional, Eiam-Ong, Somchai, additional, Elbers, Paul W.G., additional, Elli, Francesca, additional, Elliott, Steve, additional, Emlet, David R., additional, Endre, Zoltan, additional, Evans, Roger G., additional, Fanelli, Vito, additional, Fattahi, Fatemeh, additional, Federspiel, Christine Kinggaard, additional, Ferrada, Marcela A., additional, Ferrari, Fiorenza, additional, Fiaccadori, Enrico, additional, Fiorentino, Marco, additional, Fisher, Caleb, additional, Flessner, Michael F., additional, Formica, Marco, additional, Forni, Lui G., additional, Francoz, Claire, additional, French, Craig, additional, Fuhrman, Dana Y., additional, Fumagalli, Giordano, additional, Galbusera, Miriam, additional, Gallieni, Maurizio, additional, Gammill, Hilary S., additional, Gao, Dayong, additional, Garzotto, Francesco, additional, Gatta, Giuseppe, additional, Genga, Kelly R., additional, Genovesi, Simonetta, additional, Genyk, Yuri S., additional, Geradin, Christel, additional, Gesualdo, Loreto, additional, Giavarina, Davide, additional, Giuliani, Anna, additional, Glezerman, Ilya G., additional, Goldstein, Stuart L., additional, Golper, Thomas A., additional, Gómez, Hernando, additional, Granata, Antonio, additional, Grandaliano, Giuseppe, additional, Grasselli, Giacomo, additional, Groeneveld, A.B. Johan, additional, Guerci, Philippe, additional, Gunnerson, Kyle J., additional, Harbord, Nikolas, additional, Harshman, Lyndsay A., additional, Hennessy, Anthony J., additional, Hill, Graham L., additional, Hobson, Charles, additional, Hohenstein, Bernd, additional, Honoré, Patrick M., additional, Horwitz, Edward, additional, Hosseinian, Leila, additional, Hoste, Eric A.J., additional, House, Andrew A., additional, Humes, H. David, additional, Husain-Syed, Faeq, additional, Ince, Can, additional, Ing, Todd S., additional, Jacobs, Rita, additional, Jaswal, Dharmvir, additional, Jeyabalan, Arun, additional, Joannes-Boyau, Olivier, additional, Joannidis, Michael, additional, Joyce, Emily, additional, Kane-Gill, Sandra L., additional, Kaplan, Lewis J., additional, Kashani, Kianoush, additional, Katz, Nevin, additional, Kellum, John A., additional, Khanna, Ramesh, additional, Kim-Campbell, Nahmah, additional, King, Joshua D., additional, Kirwan, Christopher J., additional, Kiss, Joseph E., additional, Klein, David, additional, Kotanko, Peter, additional, Krediet, Raymond T., additional, Kuhlmann, Martin K., additional, Kuiper, Jan Willem, additional, Lachance, Philippe, additional, Lameire, Norbert, additional, Langer, Thomas, additional, Lankadeva, Yugeesh R., additional, Laurin, Louis-Philippe, additional, Lazzeri, Elena, additional, Leblanc, Martine, additional, Lefebvre, Joannie, additional, Lentini, Paolo, additional, Leray-Moragués, Hélène, additional, Levin, Adeera, additional, Lew, Susie Q., additional, Liapis, Helen, additional, Liu, Kathleen D., additional, Livigni, Sergio, additional, Locatelli, Francesco, additional, Lorenzin, Anna, additional, Lu, Jian-Da, additional, Lu, Renhua, additional, Lysak, Nicholas, additional, Macedo, Etienne, additional, Madan, Niti, additional, Madore, François, additional, Maerz, Linda L., additional, Maiden, Matthew J., additional, Malhotra, Rakesh, additional, Marengo, Marita, additional, Mariano, Filippo, additional, Marik, Paul E., additional, Marini, John J., additional, Marino, Rossella, additional, Marshall, Mark R., additional, Mårtensson, Johan, additional, Matsuura, Ryo, additional, May, Clive N., additional, Mazzone, Patrizio, additional, McCauley, Jerry, additional, McCullough, Peter A., additional, McMahon, Blaithin A., additional, Mehta, Ravindra L., additional, Mele, Caterina, additional, Menon, Madhav, additional, Meola, Mario, additional, Mérouani, Aicha, additional, Meuwly, Jean-Yves, additional, Milla, Paola, additional, Misra, Madhukar, additional, Misra, Paraish S., additional, Mizock, Barry A., additional, Modi, Jwalant R., additional, Moeckel, Gilbert, additional, Molitoris, Bruce A., additional, Morabito, Santo, additional, Mucelli, Roberto Pozzi, additional, Murray, Patrick T., additional, Murugan, Raghavan, additional, Nadim, Mitra K., additional, Nair, Devika, additional, Nalesso, Federico, additional, Neri, Mauro, additional, Nguyen, Trung C., additional, Ni, Zhaohui, additional, Noris, Marina, additional, Novick, Tessa, additional, O'Horo, John C., additional, Okusa, Mark Douglas, additional, Opal, Steven M., additional, Opdam, Helen Ingrid, additional, Ostermann, Marlies, additional, Ottaviano, Emerenziana, additional, Oudemans-van Straaten, Heleen M., additional, Overgaard-Steensen, Christian, additional, Padalino, Massimo A., additional, Panichi, Vincenzo, additional, Parameswaran, Priyanka, additional, Patel, Samir S., additional, Payen, Didier, additional, Pea, Federico, additional, Peacock, W. Frank, additional, Peart, Sandrica Young, additional, Peerapornratana, Sadudee, additional, Pelosi, Paolo, additional, Peng, Zhi-Yong, additional, Perico, Norberto, additional, Peruzzi, Licia, additional, Pesce, Francesco, additional, Pesenti, Antonio, additional, Petrucci, Ilaria, additional, Pham, Phuong-Chi, additional, Pham, Phuong-Thu, additional, Phoon, Richard K.S., additional, Piano, Salvatore, additional, Pinsky, Michael R., additional, Piquilloud, Lise, additional, Pistolesi, Valentina, additional, Plank, Lindsay D., additional, Plötz, Frans B., additional, Podestá, Manuel Alfredo, additional, Porta, Camillo, additional, Pozzato, Marco, additional, Prencipe, Michele, additional, Prowle, John R., additional, Puthucheary, Zudin A., additional, Qu, Lirong, additional, Rachoin, Jean-Sebastien, additional, Radhakrishnan, Jai, additional, Ranieri, V. Marco, additional, Ratanarat, Ranistha, additional, Remuzzi, Giuseppe, additional, Resnick, Shelby, additional, Rewa, Oleksa G., additional, Ricci, Zaccaria, additional, Ridel, Christophe, additional, Rifai, Kinan, additional, Ring, Troels, additional, Rizo-Topete, Lilia M., additional, Roessler, Eric, additional, Romagnani, Paola, additional, Romagnoli, Stefano, additional, Ronco, Claudio, additional, Ronco, Federico, additional, Rosner, Mitchell H., additional, Rossetti, Emanuele, additional, Russell, James A., additional, Saab, Georges, additional, Sabatino, Alice, additional, Saboo, Sonali S., additional, Samoni, Sara, additional, Sappington, Penny Lynn, additional, Sartori, Marco, additional, Savige, Judy, additional, Schena, Francesco Paolo, additional, Schneider, Antoine Guillaume, additional, Schraverus, Pieter, additional, Schulte, Wibke, additional, Segoloni, Giuseppe, additional, Semler, Matthew W., additional, Sharma, Aashish, additional, Shaw, Andrew, additional, Sheth, Naitik, additional, Shukla, Ashutosh, additional, Siddall, Eric C., additional, Sievers, Theodore M., additional, Siew, Edward D., additional, Singbartl, Kai, additional, Singer, Mervyn, additional, Singh, Pooja, additional, Smith, Loren E., additional, Soni, Sachin S., additional, Soto, Mara Serrano, additional, Spapen, Herbert D., additional, Srisawat, Nattachai, additional, Srivastava, Ajay, additional, Stellin, Giovanni, additional, Symons, Jordan M., additional, Szamosfalvi, Balazs, additional, Tai, Kian Bun, additional, Takalkar, Unmesh V., additional, Teitelbaum, Isaac, additional, Tetta, Ciro, additional, Thakar, Charuhas V., additional, Tonon, Marta, additional, Trepiccione, Francesco, additional, Triulzi, Darrell, additional, Tushar, Chopra, additional, Uchino, Shigehiko, additional, Valika, Ali, additional, Van Biesen, Wim, additional, Vandenberghe, Wim, additional, Vanholder, Raymond, additional, Vanmassenhove, Jill, additional, Verbine, Anton, additional, Vergano, Marco, additional, Villa, Gianluca, additional, Villeneuve, Pierre-Marc, additional, Vincent, Jean-Louis, additional, Vinsonneau, Christophe, additional, Virzì, Grazia Maria, additional, Visconti, Federico, additional, Visvanathan, Ravindran, additional, Van Vong, Li, additional, Walmrath, Hans-Dieter, additional, Ward, Peter A., additional, Weir, Matthew A., additional, Wen, Xiaoyan, additional, Wendon, Julia, additional, Winchester, James Frank, additional, Wong, Adrian, additional, Woodhouse, Elke L., additional, Xue, Jun, additional, Yadav, Anju, additional, Yerram, Preethi, additional, Yessayan, Lenar, additional, Yeun, Jane Y., additional, Yu, Alex W., additional, Zaccaria, Marta, additional, Zacchia, Miriam, additional, Zachariah, Teena P., additional, Zamperetti, Nereo, additional, Zampieri, Fernando G., additional, Zanco, Pierluigi, additional, Zanella, Alberto, additional, Zanoli, Luca, additional, Zappitelli, Michael, additional, Zaragoza, Jose J., additional, Zarbock, Alexander, additional, Zaroccolo, Marta, additional, Zhang, Han, additional, and Zimmer, Andrea, additional

Published
2019
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45. DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity

Author

Cao, Aili, Li, Jianhua, Asadi, Morad, Basgen, John M., Zhu, Bingbing, Yi, Zhengzi, Jiang, Song, Doke, Tomohito, Shamy, Osama El, Patel, Niralee, Cravedi, Paolo, Azeloglu, Evren U., Campbell, Kirk N., Menon, Madhav, Coca, Steve, Zhang, Weijia, Wang, Hao, Zen, Ke, Liu, Zhihong, Murphy, Barbara, He, John C., D'Agati, Vivette D., Susztak, Katalin, and Kaufman, Lewis

Subjects
Physiological aspects, Development and progression, Genetic aspects, Health aspects, Diabetes mellitus -- Genetic aspects -- Development and progression, Renal corpuscle -- Physiological aspects -- Genetic aspects, Epithelial cells -- Physiological aspects -- Health aspects -- Genetic aspects, Transcription factors -- Physiological aspects -- Health aspects, Diabetes -- Genetic aspects -- Development and progression, Kidney glomerulus -- Physiological aspects -- Genetic aspects
Abstract

Introduction Dachshund homolog 1 (DACH1) was originally identified as an essential member of the retinal determination gene network (RDGN), a fundamental signal that governs cell fate during development. That DACH1 [...], Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence-specific binding. We identified diminished Dach1 expression in a large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 expression levels are diminished, a condition that strongly correlates with poor clinical outcomes. Global Dach1 KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific Dach1 KO mice, however, maintain normal glomerular architecture at baseline, but rapidly exhibit podocyte injury after diabetes onset. Furthermore, podocyte-specific augmentation of DACH1 expression in mice protects from DKD. Combined RNA sequencing and in silico promoter analysis reveal conversely overlapping glomerular transcriptomic signatures between podocyte-specific Dach1 and Pax transactivation-domain interacting protein (Ptip) KO mice, with upregulated genes possessing higher-than-expected numbers of promoter Dach7-binding sites. PTIP, an essential component of the activating histone H3 lysine 4 trimethylation (H3K4Me3) complex, interacts with DACH1 and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increases promoter H3K4Me3. These findings reveal that in DKD, diminished DACH1 expression enhances podocyte injury vulnerability via epigenetic derepression of its target genes.

Published
2021
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49. First Randomised Controlled Trial Comparing the Sirolimus-Eluting Bioadaptor with the Zotarolimus-Eluting Drug-Eluting Stent in Patients with De Novo Coronary Artery Lesions: 12-Month Clinical and Imaging Data from the Multi-Centre, International, BIODAPTOR- RCT

Author

Saito, Shigeru, primary, Bennett, Johan, additional, Nef, Holger, additional, Webster, Mark, additional, Namiki, Atsuo, additional, Takahashi, Akihiko, additional, Kakuta, Tsunekazu, additional, Yamazaki, Seiji, additional, Shibata, Yoshisato, additional, Scott, Douglas, additional, Vrolix, Mathias, additional, Menon, Madhav, additional, Möllmann, Helge, additional, Werner, Nikos, additional, Neylon, Antoinette, additional, Mehmedbegovic, Zlatko, additional, Smits, Pieter, additional, Morice, Marie-Claude, additional, Verheye, Stefan, additional, and Collaborators, BIOADAPTOR-RCT, additional

Published
2023
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