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Article ; Online: Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation.

Heilman, Raymond L / Fleming, James N / Mai, Martin / Smith, Byron / Park, Walter D / Holman, John / Stegall, Mark D

2023 Volume 37, Issue 8, Page(s) e14987

Abstract: Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation.: Methods: We conducted a prospective, multicenter ... ...

Abstract	Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p < .001) and more chronic changes on 1-year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p < .001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. Conclusions: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; Prospective Studies ; Gene Expression ; Graft Survival ; Graft Rejection/etiology ; Graft Rejection/genetics
Language	English
Publishing date	2023-04-07
Publishing country	Denmark
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.14987
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Article: Clinical management of renal transplant patients with donor-specific alloantibody: the state of the art.

Stegall, Mark D

Clinical transplants

2010 , Page(s) 307–315

Abstract: Our understanding of the role of DSA in both early and late renal allograft injury has advanced significantly over the past decade. Novel protocols have been developed that have led to improved outcomes both in overcoming a positive crossmatch and in the ...

Abstract	Our understanding of the role of DSA in both early and late renal allograft injury has advanced significantly over the past decade. Novel protocols have been developed that have led to improved outcomes both in overcoming a positive crossmatch and in the treatment of early AMR. Early experience with bortezomib and eculizumab are encouraging and suggest the possibility of validation in controlled clinical trials. While alloantibody remains an extremely difficult clinical problem and it is unclear if overcoming early hurdles will only be followed by another major hurdle of chronic antibody mediated injury. However, it is clear that significant advances have occurred and if future studies can be designed appropriately, then our ability to control alloantibody in sensitized patients will continue to improve.
MeSH term(s)	Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft Survival ; HLA Antigens/immunology ; Histocompatibility ; Histocompatibility Testing ; Humans ; Immunosuppressive Agents/therapeutic use ; Isoantibodies/blood ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Risk Assessment ; Risk Factors ; Survival Rate ; Time Factors ; Tissue Donors ; Transplantation Tolerance ; Treatment Outcome
Chemical Substances	HLA Antigens ; Immunosuppressive Agents ; Isoantibodies
Language	English
Publishing date	2010
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	607631-2
ISSN	0890-9016
ISSN	0890-9016
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Article ; Online: The right kidney for the right recipient: the status of deceased donor kidney allocation reform.

Stegall, Mark D

Seminars in dialysis

2010 Volume 23, Issue 3, Page(s) 248–252

Abstract: How best to allocate the limited number of deceased donor kidneys has been the subject of intense debate over past several months in the United States. Most of the major stakeholders have expressed their viewpoints in a series of recent publications. ... ...

Abstract	How best to allocate the limited number of deceased donor kidneys has been the subject of intense debate over past several months in the United States. Most of the major stakeholders have expressed their viewpoints in a series of recent publications. This manuscript aims to examine some of the most important issues in this discussion and to outline a possible path forward.
MeSH term(s)	Humans ; Kidney Transplantation ; Tissue Donors/supply & distribution ; Tissue and Organ Procurement/methods ; United States
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1028193-9
ISSN	1525-139X ; 0894-0959
ISSN (online)	1525-139X
ISSN	0894-0959
DOI	10.1111/j.1525-139X.2010.00723.x
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Article ; Online: Evidence that alloantibody is a major risk factor for graft loss and death in living-donor liver transplantation.

Stegall, Mark D

Surgery

2010 Volume 147, Issue 6, Page(s) 845–846

MeSH term(s)	HLA Antigens/blood ; HLA Antigens/immunology ; Heart Transplantation/immunology ; Heart Transplantation/mortality ; Humans ; Immunization/mortality ; Isoantibodies/blood ; Kidney Transplantation/immunology ; Kidney Transplantation/mortality ; Liver Transplantation/immunology ; Liver Transplantation/mortality ; Living Donors ; Risk Factors ; Treatment Failure ; Treatment Outcome
Chemical Substances	HLA Antigens ; Isoantibodies
Language	English
Publishing date	2010-06
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2009.12.001
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Article ; Online: Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells.

Yigitbilek, Furkan / Ozdogan, Elif / Abrol, Nitin / Park, Walter D / Hansen, Michael J / Dasari, Surendra / Stegall, Mark D / Taner, Timucin

Frontiers in immunology

2022 Volume 13, Page(s) 952262

Abstract: Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver's overall tolerogenic ... ...

Abstract	Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver's overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation.
MeSH term(s)	Granzymes/metabolism ; Humans ; Interleukin-2/metabolism ; Killer Cells, Natural/metabolism ; Liver/metabolism ; Mesenchymal Stem Cells/metabolism ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Perforin/metabolism ; Secretome
Chemical Substances	Interleukin-2 ; NK Cell Lectin-Like Receptor Subfamily K ; Perforin (126465-35-8) ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2022-09-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.952262
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Article: Computational Biology: Modeling Chronic Renal Allograft Injury.

Stegall, Mark D / Borrows, Richard

Frontiers in immunology

2015 Volume 6, Page(s) 385

Abstract: New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in ... ...

Abstract	New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury.
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00385
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Article ; Online: Electrocardiography-based Artificial Intelligence Algorithms Aid in Prediction of Long-term Mortality After Kidney Transplantation.

Pencovich, Niv / Smith, Byron H / Attia, Zachi I / Jimenez, Francisco Lopez / Bentall, Andrew J / Schinstock, Carrie A / Khamash, Hasan A / Jadlowiec, Caroline C / Jarmi, Tambi / Mao, Shennen A / Park, Walter D / Diwan, Tayyab S / Friedman, Paul A / Stegall, Mark D

Transplantation

2024

Abstract: Background: Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative ... ...

Abstract	Background: Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT. Methods: We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data. Results: Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality (P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751). Conclusions: The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000005023
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Clinical outcomes after ABO-incompatible renal transplantation.

Loupy, Alexandre / Bouquegneau, Antoine / Stegall, Mark D / Montgomery, Robert A

Lancet (London, England)

2019 Volume 394, Issue 10213, Page(s) 1988–1989

MeSH term(s)	Blood Group Incompatibility ; Graft Survival ; Kidney Transplantation
Language	English
Publishing date	2019-12-01
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(19)32490-0
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Article ; Online: The need for novel trial designs, master protocols, and research consortia in transplantation.

Stegall, Mark D / Smith, Byron / Bentall, Andrew / Schinstock, Carrie

Clinical transplantation

2019 Volume 34, Issue 1, Page(s) e13759

Abstract: Large multicenter, randomized controlled trials are the paradigm for determining the efficacy and safety of new therapies. However, applying this classical approach to many areas of transplantation is difficult. For most types of organ transplants, the ... ...

Abstract	Large multicenter, randomized controlled trials are the paradigm for determining the efficacy and safety of new therapies. However, applying this classical approach to many areas of transplantation is difficult. For most types of organ transplants, the number of transplants performed is too small for such a trial (lung, pancreas, or vascular composite transplantation are examples). In larger populations such as kidney transplantation, the major unmet needs commonly involve small subsets of patients (antibody-mediated rejection, recurrent renal disease, etc). This issue is not unique to transplantation and has been successfully overcome in other areas of medicine. In oncology, for example, novel trial designs such as adaptive trial design and master protocols are now relatively common. In addition, the existence of multicenter, ongoing clinical research consortia have greatly enhanced the successful implementation of these novel trial designs. In this manuscript, we examine how novel trial designs, master protocols, and research consortia might enhance studies in transplantation aimed at the regulatory approval of new agents. Our premise is that more efficient approaches to clinical trials already exist and, through a coordinated effort by researchers, the pharmaceutical industry, and regulatory bodies like the FDA, they can be implemented in transplantation.
MeSH term(s)	Humans ; Kidney Transplantation ; Multicenter Studies as Topic ; Research Design
Language	English
Publishing date	2019-12-31
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.13759
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Article ; Online: Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity.

Kukla, Aleksandra / Sahi, Sukhdeep S / Navratil, Pavel / Benzo, Roberto P / Smith, Byron H / Duffy, Dustin / Park, Walter D / Shah, Meera / Shah, Pankaj / Clark, Matthew M / Fipps, David C / Denic, Aleksandar / Schinstock, Carrie A / Dean, Patrick G / Stegall, Mark D / Kudva, Yogish C / Diwan, Tayyab S

Mayo Clinic proceedings

2024 Volume 99, Issue 5, Page(s) 705–715

Abstract: Objective: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT.: Methods: Retrospective analysis was conducted of electronic medical records of KT candidates with ... ...

Abstract	Objective: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT. Methods: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m Results: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m Conclusion: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT.
MeSH term(s)	Humans ; Kidney Transplantation ; Male ; Female ; Retrospective Studies ; Middle Aged ; Obesity/surgery ; Obesity/complications ; Bariatric Surgery/methods ; Adult ; Weight Loss ; Gastrectomy/methods ; Gastrectomy/adverse effects ; Body Mass Index ; Treatment Outcome ; Kidney Failure, Chronic/surgery
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2024.01.017
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