A5031813099- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Renal Diseases and Glomerulopathies
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Complement system in diseases
- Drug-Induced Adverse Reactions
- HIV/AIDS drug development and treatment
- Multiple Myeloma Research and Treatments
- Pharmacological Effects and Toxicity Studies
- Organ Donation and Transplantation
- Immune Cell Function and Interaction
- Renal and Vascular Pathologies
- Liver Disease and Transplantation
- Pneumocystis jirovecii pneumonia detection and treatment
- Metabolism and Genetic Disorders
- Acute Kidney Injury Research
- Biological Research and Disease Studies
- Organ and Tissue Transplantation Research
- Hematopoietic Stem Cell Transplantation
- Hepatitis C virus research
- Immunodeficiency and Autoimmune Disorders
- Hepatitis B Virus Studies
- Transplantation: Methods and Outcomes
- Xenotransplantation and immune response
University of Cincinnati
2010-2024
Christ Hospital
2013-2024
University of Cincinnati Medical Center
2011-2023
Christ Hospital
2014-2023
The efficacy of plasma cell targeted therapies for antibody-mediated rejection (AMR) has not been defined in detail. purpose this study was to compare early and late acute AMR terms immunologic characteristics responses with proteasome inhibitor (PI) therapy.Renal transplant recipients were treated PI-based regimens. Early as occurring within 6 months posttransplant. Immunodominant donor-specific antibody (iDSA) the DSA highest level.Results are expressed or AMR. Thirty episodes (13 early,...
A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose plasmapheresis. Abs were measured by solid phase flow cytometry (FCM) assays. Immunodominant Ab (iAb) defined as highest level. Forty-four patients received 52 desensitization courses (7 enrolled multiple phases):...
Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked context critical to mechanistic understanding how occurs despite immunosuppression (IS). We performed combined single-cell transcriptomic and TCR-α/β sequencing on rBx from patients ACR under differing IS drugs: tacrolimus, iscalimab, belatacept. found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon type,...
Significance Statement Single-center trials and retrospective case series have reported promising outcomes transplanting kidneys from donors with hepatitis C virus (HCV) infection into HCV-negative recipients, although concerns remain about immunologic complications. In this first multicenter trial, 30 HCV-uninfected adults received a kidney an HCV-viremic deceased donor were cured of HCV 8-week regimen coformulated glecaprevir pibrentasvir initiated 2–5 days post-transplant. Three patients...
Proteasome inhibitor–based strategies hold promise in transplant but have yielded varying results. Carfilzomib, a second-generation proteasome inhibitor, may possess advantages over bortezomib, the first-generation inhibitors. The purpose of this study was to evaluate safety, toxicity, and preliminary efficacy carfilzomib highly HLA-sensitized kidney candidates. Renal candidates received escalating doses followed by plasmapheresis (group A) or an identical regimen with additional once weekly...
Simultaneous calcineurin inhibitor avoidance (CNIA) and early corticosteroid withdrawal (ESW) have not been achieved primarily due to excessive acute rejection. This trial compared 2 belatacept-based CNIA/ESW regimens with a tacrolimus-based ESW regimen. Kidney transplant recipients were randomized receive alemtuzumab/belatacept, rabbit anti-thymocyte globulin (rATG)/belatacept, or rATG/tacrolimus. The combinatorial primary endpoint consisted of patient death, renal allograft loss,...
Morbid obesity is a barrier to kidney transplantation due inferior outcomes, including higher rates of new-onset diabetes after (NODAT), delayed graft function (DGF), and failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in candidates, but the effect surgical weight loss on posttransplantation outcomes unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before from 2011-2016 (n = 20). Post-LSG recipients...
A prospective intermediate-term evaluation of toxicities associated with bortezomib therapy for antibody-mediated rejection (AMR) and desensitization was conducted.Patients were graded bortezomib-related toxicities: hematologic gastrointestinal by Common Terminology Criteria Adverse Events peripheral neuropathy modified Functional Assessment Cancer Therapy questionnaire Events.Fifty-one patients treated AMR 19 received 96 cycles (1.3 mg/m(2) ×4 doses); mean (SD) follow-up 16.3 (9.0) months....
Optimal induction regimens for patients at high risk antibody and/or cell–mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell–targeting agents to T cell–based with rabbit antithymocyte globulin (rATG) in immunologic renal transplant recipients. Patients were rATG, rATG + rituximab, bortezomib or rituximab bortezomib. Inclusion criteria were: (1) current cytotoxic panel reactive (PRA) ≥20% peak PRA ≥50% (2) cell...
Background and objectives Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T-cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared calcineurin inhibitor–based immunosuppression. The efficacy safety of simultaneous inhibitor avoidance rapid steroid withdrawal were tested a randomized, prospective, multicenter study. Design, setting, participants, & measurements This study reports the 2-year...
Abstract Background Severe obesity has been shown to limit access renal transplantation in patients with end‐stage disease ( ESRD ). Laparoscopic sleeve gastrectomy LSG ) performed the population assist achieving waitlist and transplant eligibility. Little is known about how impacts bioequivalence of tacrolimus products immunosuppression pharmacokinetics. Methods This was a prospective, open‐label, single‐dose, crossover, two‐period pharmacokinetic PK study. The purpose this study assess...
The cellular events that contribute to generation of donor-specific anti-HLA antibodies (DSA) post-kidney transplantation (KTx) are not well understood. Characterization such mechanisms could allow tailoring immunosuppression benefit sensitized patients.We prospectively monitored circulating T follicular helper (cTFH) cells in KTx recipients who received T-cell depleting (thymoglobulin, n = 54) or nondepleting (basiliximab, 20) induction therapy from pre-KTx 1 year post-KTx and assessed...
Background. Renal allograft rejection is more frequent under belatacept-based, compared with tacrolimus-based, immunosuppression. We studied kidney transplant recipients experiencing belatacept-based early corticosteroid withdrawal following T-cell–depleting induction in a recent randomized trial (Belatacept-based Early Steroid Withdrawal Trial, clinicaltrials.gov NCT01729494) to determine mechanisms of and treatment. Methods. Peripheral mononuclear cells, serum creatinine levels, renal...
Background: Contrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase mortality and morbidity. Data regarding CIN renal allografts limited however. We retrospectively studied at our institution: its incidence, risk factors effect on long-term outcomes including allograft loss death. Methods: 135 transplant recipients undergoing 161 contrast-enhanced CT scans (CT) or coronary angiograms (Cath) between years 2000 2013 were identified. Contrast agents iso-...
Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not separately analyzed for early and late AMR mixed acute (MAR). The purpose of this study was to evaluate long-term responses proteasome inhibitor-based therapy 4 phenotypes determine factors that predict survival.Retrospective cohort evaluating transplant recipients first episodes treated from January 2005 July 2015.A total...
In Brief Background Histology remains a cornerstone for antibody-mediated rejection (AMR) diagnosis. Little data exist supporting histology assessing therapeutic responses. This study evaluates histologic components in AMR Methods Antibody-mediated was diagnosed using Antibody Working Group criteria and Banff component scoring, C4d staining were analyzed. Statistics included independent paired samples t test, χ2, Fisher exact, or the Wilcoxon-signed rank test. Fifty-five patients Early...
Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked context critical to mechanistic understanding. We performed combined single cell transcriptomic and TCRα/β sequencing on rBx from patients ACR under differing immunosuppression (IS): tacrolimus, iscalimab, belatacept. TCR revealed a highly restricted CD8 + T clonal expansion (CD8 EXP ), independent HLA mismatch or IS type. Subcloning cDNAs into...
Belatacept, a fusion protein immunosuppressant, may be removed by plasmapheresis (PP) in clinically significant amount. Scenarios arise requiring concurrent PP patients maintained on belatacept; however, clinical guidance for dosing remains an unmet need. We propose supplemental strategy of belatacept the setting PP. Kidney transplant (KT) recipients included received de novo as part BEST (Belatacept Early Steroid Withdrawal Trial) randomized controlled trial at University Cincinnati Medical...
Walsh, R. C.; Shields, A. R.; Girnita, A.; Wall, G. E.; Brailey, P.; Arend, L.; Cardi, M.; Govil, Tevar, Safdar, S.; Alloway, Woodle, E. S. Author Information
Walsh, R. C.; Shields, A. R.; Mogilishetty, G.; Govil, A.; Roy-Chaudhury, P.; Young, S.; Wall, G. E.; Safdar, Huang, Cardi, M.; Alloway, Woodle, E. S. Author Information