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Leal R, Fragoso P, Venda J, Gomes J, Inácio M, Guedes Marques M, Rodrigues L, Santos L, Romãozinho C, Caramelo F, Sá HO, Martinho A, Figueiredo A, Alves R. Prolonging calcineurin inhibitor therapy post kidney allograft failure: a prospective study. Ren Fail 2025; 47:2483386. [PMID: 40159821 PMCID: PMC11960309 DOI: 10.1080/0886022x.2025.2483386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/28/2025] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND The optimal immunosuppressive (IS) withdrawal strategy after kidney allograft failure remains unclear. This study evaluated the effects of prolonged calcineurin inhibitor (CNI) therapy on HLA sensitization, graft intolerance syndrome (GIS), and key clinical outcomes. METHODS We conducted a prospective cohort study involving 90 adult patients with kidney allograft failure who were candidates for re-transplantation. Patients were divided into two groups: Rapid withdrawal group (discontinuation of all IS except low-dose prednisolone) and Prolonged CNI Group (maintenance of CNI for six months plus low-dose prednisolone). Outcomes assessed over a 12-month follow-up period included HLA sensitization, defined as an increase in calculated panel reactive antibody (cPRA) and the development of de novo donor-specific antibodies (dnDSA), GIS incidence, re-transplantation, hospitalization rates, and mortality. RESULTS No significant differences were observed between the groups regarding HLA sensitization one-year postgraft failure. A composite outcome of cPRA increase, dnDSA, and GIS did not differ between the groups. When evaluated separately, GIS occurred less frequently in the Prolonged CNI Group (4.8% vs. 23%; p = 0.015). Patients who continued CNI maintained better residual kidney function at 6 months (800 vs. 200 mL, p = 0.001) and experienced lower all-cause hospitalization rates (12% vs. 30%, p = 0.036), with comparable retransplantation and mortality rates. Graft removal and higher HLA mismatches were independently linked to increased sensitization at 12 months. CONCLUSIONS Prolonged CNI therapy for six months postallograft loss did not prevent HLA sensitization but reduced the incidence of GIS and preserved residual kidney function without increasing hospitalization or mortality.
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Affiliation(s)
- Rita Leal
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Pedro Fragoso
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
| | - João Venda
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
| | - José Gomes
- Centro de Histocompatibilidade do Centro, Instituto Português do Sangue e Transplantação, Coimbra, Portugal
| | - Maria Inácio
- Centro de Histocompatibilidade do Centro, Instituto Português do Sangue e Transplantação, Coimbra, Portugal
| | - Maria Guedes Marques
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Luís Rodrigues
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Lídia Santos
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Catarina Romãozinho
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | | | - Helena Oliveira Sá
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - António Martinho
- Centro de Histocompatibilidade do Centro, Instituto Português do Sangue e Transplantação, Coimbra, Portugal
| | - Arnaldo Figueiredo
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Urology and Kidney Transplantation Unit, ULS-Coimbra, Coimbra, Portugal
| | - Rui Alves
- Nephrology Department, ULS-Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Beyer AP, Moise PA, Wong M, Gao W, Xiang C, Shen P, Pavlakis M, Vincenti F, Wang W. Clinical events and healthcare resource utilization associated with neutropenia and leukopenia among adult kidney transplant recipients receiving valganciclovir. World J Transplant 2025; 15:102671. [DOI: 10.5500/wjt.v15.i2.102671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 12/09/2024] [Accepted: 01/23/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients, although the impact of these events on healthcare resource utilization (HCRU) and clinical outcomes is unclear.
AIM To quantify clinical events and HCRU associated with neutropenia and leukopenia among adults receiving valganciclovir and/or ganciclovir post-kidney transplantation.
METHODS Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021. Patient characteristics were evaluated in the 1-year period pre-first transplant. HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.
RESULTS Of 15398 identified patients, the average age was 52.39 years and 58.70% were male. Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events, opportunistic infections, use of granulocyte colony stimulating factor, and hospitalizations (relative risk > 1 in year 1 and years 2-5). Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation, including the mean number of inpatient admissions (year 1: 3.47 vs 2.76; years 2-5: 2.70 vs 2.29) and outpatient visits (48.97 vs 34.42; 31.73 vs 15.59, respectively), as well as the mean number of labs (1654.55 vs 1182.27; 622.37 vs 327.89).
CONCLUSION Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia, which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation. These findings suggest the need for alternative prophylaxis options with lower myelosuppressive effects to improve patient outcomes.
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Affiliation(s)
- Andrew P Beyer
- Department of Value and Implementation Outcomes Research, Merck & Co., Inc., Rahway, NJ 07065, United States
| | - Pamela A Moise
- Medical Affairs, Merck & Co., Inc., Rahway, NJ 07065, United States
| | - Michael Wong
- Scientific Affairs, Merck & Co., Inc., Rahway, NJ 07065, United States
| | - Wei Gao
- Analysis Group, Boston, MA 02199, United States
| | | | | | - Martha Pavlakis
- The Transplant Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Flavio Vincenti
- The Transplant Services, University of California San Francisco, San Francisco, CA 94143, United States
| | - Weijia Wang
- Department of Value and Implementation Outcomes Research, Merck & Co., Inc., Rahway, NJ 07065, United States
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Ayvaci MUS, Giacoma T, Abouljoud MS, Tanriover B. The economic value of a transplant nephrologist: The case for improving compensation models. Am J Transplant 2025; 25:1156-1162. [PMID: 40090416 DOI: 10.1016/j.ajt.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 03/08/2025] [Accepted: 03/10/2025] [Indexed: 03/18/2025]
Abstract
This article examined the economic value of transplant nephrologists and the need for adequate compensation. Kidney transplantation is a health and lifespan-extending procedure that relies on the expertise of transplant nephrologists. However, current compensation models, primarily based on relative value units (RVUs), often fail to capture the full scope of their work, particularly nonbillable activities essential to patient care. Additionally, regulatory compliance issues, particularly those related to the physician self-referral law (also known as the Stark law), complicate compensation structures. The Stark law mandates that physician compensation must align with fair market value to avoid conflicts of interest, adding complexity to designing compensation packages that accurately reflect the value of transplant nephrologists' contributions. This article critiques the RVU-based system, highlighting its limitations in adequately compensating these specialists and proposing solutions such as integrating customized RVUs and outcome value units to better account for nonbillable work and incentivize high-quality care. The use of Medicare organ acquisition cost reports is also suggested to align compensation more closely with the actual economic value generated. A comprehensive approach that addresses both the quantitative and qualitative aspects of transplant nephrologists' work, while navigating regulatory requirements, is essential for adequate and equitable compensation.
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Affiliation(s)
- Mehmet U S Ayvaci
- Jindal School of Management, The University of Texas at Dallas, Richardson, Texas, USA
| | | | - Marwan S Abouljoud
- Transplant Institute and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan, USA
| | - Bekir Tanriover
- Division of Nephrology, Department of Internal Medicine, The University of Arizona College of Medicine, Tucson, Arizona, USA.
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Wagner N, Angeloni M, Ferrazzi F, Müller-Deile J, Büttner-Herold M, Amann K, Daniel C, Vonbrunn E. Hypertension in living kidney donors has no effect on complement activation and fibrosis. Kidney Blood Press Res 2025; 50:1-21. [PMID: 40341498 PMCID: PMC12165627 DOI: 10.1159/000545750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/02/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND In the past, elevated blood pressure was considered an exclusion criterion for living kidney donation because of concerns about premature kidney failure. Hypertension leads to complement deposits and renal fibrosis in the kidney. Therefore, the aim of this study was to investigate whether increased complement deposits and fibrosis can be observed in grafts of hypertensive compared to normotensive living donors. METHODS Zero-time renal biopsies from 238 living donors (52 hypertensive) and the corresponding one-year protocol biopsies were examined for complement deposits of C1q, C3c, and MASP-2. Findings were compared to kidney biopsies from patients with hypertensive nephropathy. Further, renal fibrosis was visualized by Sirius Red staining, scored semiquantitatively and compared to biopsies from deceased donors and kidneys with hypertensive nephropathy. Additionally, zero-time biopsies from hypertensive (n = 6) and normotensive (n = 5) living donors were analyzed for expression of fibrosis-associated genes by multiplex mRNA analysis and compared to zero-time biopsies (n = 6) from deceased donors. RESULTS In all zero-time biopsies from living donors, complement deposits were minimal for C1q, C3c, and MASP-2 compared to samples with hypertensive nephropathy, regardless of whether the donor was hypertensive or normotensive. In one-year protocol biopsies, complement deposits were unchanged, while renal fibrosis was slightly but not significantly increased in hypertensive compared to normotensive living donors. Gene expression data showed that the 11 zero-time biopsies from hypertensive and normotensive living donors clustered together, and were clearly separated from the deceased donor biopsies. CONCLUSION The use of kidneys from hypertensive living donors appears to have no or little effect on renal complement deposits and fibrosis one year after transplantation.
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Affiliation(s)
- Nadine Wagner
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Miriam Angeloni
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Fulvia Ferrazzi
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Janina Müller-Deile
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Maike Büttner-Herold
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Kerstin Amann
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Christoph Daniel
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Eva Vonbrunn
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
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Yang J, Yang H, An Z. Catatonia related to tacrolimus: a real world pharmacovigilance study of FDA adverse event reporting system (FAERS) database. Expert Opin Drug Saf 2025; 24:595-598. [PMID: 39152414 DOI: 10.1080/14740338.2024.2393757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/18/2024] [Accepted: 04/22/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Emerging case reports have highlighted that catatonia may be a complication that is easily misdiagnosed. Our study aimed to summarize the clinical characteristics of patients with tacrolimus-induced catatonia and assess the association between tacrolimus and catatonia through disproportionality analysis. RESEARCH DESIGN AND METHODS We conducted a retrospective pharmacovigilance study using the FAERS database, analyzing data up to the third quarter of 2023. The clinical characteristics of the reported cases were summarized using descriptive statistics. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between tacrolimus and catatonia. RESULTS There were 66 reports of tacrolimus-related catatonia, with the majority of cases occurring in the United States (78.79%). The risk signal for tacrolimus-related catatonia was significantly higher compared to all other drugs (ROR 3.222 [2.524, 4.111], IC 1.632 [1.273, 1.991]). A significant association was detected in both male and female, while the risk signal of tacrolimus-associated catatonia was only found in the subgroups aged over 40 years. CONCLUSIONS Our study identified a safety signal for the association between tacrolimus and catatonia compared to all other drugs in FAERS database, particularly in patients aged 40 and above.
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Affiliation(s)
- Jing Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, CN, China
| | - Hui Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, CN, China
| | - Zhuoling An
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, CN, China
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Myaskovsky L, Leyva Y, Puttarajappa C, Kalaria A, Ng YH, Vélez-Bermúdez M, Zhu Y, Bryce C, Croswell E, Wesselman H, Kendall K, Chang CC, Boulware LE, Tevar A, Dew MA. Kidney Transplant Fast Track and Likelihood of Waitlisting and Transplant: A Nonrandomized Clinical Trial. JAMA Intern Med 2025; 185:499-509. [PMID: 40063052 PMCID: PMC11894542 DOI: 10.1001/jamainternmed.2025.0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 12/20/2024] [Indexed: 03/14/2025]
Abstract
Importance Kidney transplant (KT) is the optimal treatment for end-stage kidney disease (ESKD). The evaluation process for KT is lengthy, time-consuming, and burdensome, and racial and ethnic disparities persist. Objective To investigate the potential association of the Kidney Transplant Fast Track (KTFT) evaluation approach with the likelihood of waitlisting, KT, and associated disparities compared with standard care. Design, Setting, and Participants This nonrandomized clinical trial was a prospective comparative cohort trial with a historical control (HC) comparison and equal follow-up duration at a single urban transplant center. Study duration was 2015 to 2018 for KTFT, with follow-up through 2022, and 2010 to 2014 for HC, with follow-up through 2018. Adult, English-speaking patients with ESKD, no history of KT, and a scheduled KT evaluation appointment were included. Among 1472 eligible patients for the KTFT group, 1288 consented and completed the baseline interview and 170 were excluded for not attending an evaluation appointment; among 1337 patients eligible for the HC group, 1152 consented and completed the baseline interview and none were excluded. Data were analyzed from August 2023 through December 2024. Exposure Streamlined, patient-centered, coordinated-care KT evaluation process. Main Outcomes and Measures Time to waitlisting for KT and receipt of KT. Results The study included 1118 participants receiving KTFT (416 female [37.2%]; mean [SD] age, 57.2 [13.2] years; 245 non-Hispanic Black [21.9%], 790 non-Hispanic White [70.7%], and 83 other race or ethnicity [7.4%]) and 1152 participants in the HC group (447 female [38.8%]; mean [SD] age, 55.5 [13.2] years; 267 non-Hispanic Black [23.2%], 789 non-Hispanic White [68.5%], and 96 other race or ethnicity [8.3%]). After adjusting for demographic and clinical factors, the KTFT compared with the HC group had a higher likelihood of being placed on the active waitlist for KT (subdistribution hazard ratio [SHR], 1.40; 95% CI, 1.24-1.59). Among individuals who were waitlisted, patients in the KTFT vs HC group had a higher likelihood of receiving a KT (SHR, 1.21; 95% CI, 1.04-1.41). Black patients (SHR, 1.54; 95% CI, 1.11-2.14) and White patients (SHR, 1.38; 95% CI, 1.16-1.65) receiving KTFT were more likely to be waitlisted for KT than those in the HC group, but no such difference was found for patients with other race or ethnicity. Among Black patients, those with KTFT were more likely than those in the HC group to undergo KT (SHR, 1.52; 95% CI, 1.06-2.16), but no significant differences were found for White patients or those with other race or ethnicity. Conclusions and Relevance This study found that KTFT was associated with a higher likelihood of waitlisting and KT than standard care. Findings suggest that KTFT may be associated with reduced disparities in KT by race and ethnicity. Trial Registration ClinicalTrials.gov Identifier: NCT02342119.
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Affiliation(s)
- Larissa Myaskovsky
- Center for Healthcare Equity in Kidney Disease, University of New Mexico Health Sciences Center, Albuquerque
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque
| | - Yuridia Leyva
- Center for Healthcare Equity in Kidney Disease, University of New Mexico Health Sciences Center, Albuquerque
| | - Chethan Puttarajappa
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Arjun Kalaria
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Now with Florida Kidney Physicians, Tampa
| | - Yue-Harn Ng
- Department of Medicine, University of Washington School of Medicine, Seattle
| | - Miriam Vélez-Bermúdez
- Center for Healthcare Equity in Kidney Disease, University of New Mexico Health Sciences Center, Albuquerque
| | - Yiliang Zhu
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque
| | - Cindy Bryce
- Department of Health Policy and Management, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
| | - Emilee Croswell
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | | | - Chung-Chou Chang
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
- Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
| | | | - Amit Tevar
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Mary Amanda Dew
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
- Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Acute and Tertiary Care, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania
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Aarattuthodi S, Kang D, Gupta SK, Chen P, Redel B, Matuha M, Mohammed H, Sinha AK. Cryopreservation of biological materials: applications and economic perspectives. In Vitro Cell Dev Biol Anim 2025:10.1007/s11626-025-01027-0. [PMID: 40266443 DOI: 10.1007/s11626-025-01027-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/09/2025] [Indexed: 04/24/2025]
Abstract
Cryopreservation is a transformative technology that allows for the long-term storage of biological materials by cooling them to extremely low temperatures at which metabolic and biochemical processes are effectively slowed or halted. Cryopreservation utilizes various techniques to minimize ice crystal formation and cellular damage during freezing and thawing processes. This technology has broad applications in the fields of medicine, agriculture, and conservation, spanning across stem cell research, reproductive and regenerative medicine, organ transplantation, and cell-based therapies, each with significant economic implications. While current techniques and their associated costs present certain challenges, ongoing research advancements related to cryoprotectants, cooling methods, and automation promise to enhance efficiency and accessibility, potentially broadening the technology's impact across various sectors. This review focuses on the applications of cryopreservation, research advancements, and economic implications, emphasizing the importance of continued research to overcome the current limitations.
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Affiliation(s)
- Suja Aarattuthodi
- Plant Genetics Research Unit, United States Department of Agriculture - Agricultural Research Service, Columbia, MO, 65211, USA.
| | - David Kang
- Biological Control of Insects Research Laboratory, United States Department of Agriculture - Agricultural Research Service, Columbia, MO, 65211, USA
| | - Sanjay Kumar Gupta
- Indian Institute of Agricultural Biotechnology, Garhkhatanga, Ranchi, Jharkhand, 834003, India
| | - Paula Chen
- Plant Genetics Research Unit, United States Department of Agriculture - Agricultural Research Service, Columbia, MO, 65211, USA
| | - Bethany Redel
- Plant Genetics Research Unit, United States Department of Agriculture - Agricultural Research Service, Columbia, MO, 65211, USA
| | - Moureen Matuha
- Department of Agriculture and Environmental Sciences, Lincoln University of Missouri, Jefferson City, MO, 65101, USA
| | - Haitham Mohammed
- Department of Rangeland, Wildlife and Fisheries Management, Texas a&M University, College Station, TX, 77843, USA
| | - Amit Kumar Sinha
- Department of Aquaculture and Fisheries, University of Arkansas Pine Bluff, Pine Bluff, AR, 71601, USA
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Massey EK. Unmet Educational and Psychosocial Support Needs After Graft Loss: A Call for Clarity and Compassion. Transplantation 2025:00007890-990000000-01060. [PMID: 40211104 DOI: 10.1097/tp.0000000000005413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2025]
Affiliation(s)
- Emma K Massey
- Department of Internal Medicine, Erasmus MC Transplant Institute, Rotterdam, the Netherlands
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Duarte S, Fassler AM, Willman M, Lewis D, Warren C, Angeli-Pahim I, Shah R, Vrakas G, El Hinnawi A, De Faria W, Beduschi T, Battula N, Zarrinpar A. Soluble DNA Concentration in the Perfusate is a Predictor of Posttransplant Renal Function in Hypothermic Machine Perfused Kidney Allografts. Transplant Direct 2025; 11:e1768. [PMID: 40124244 PMCID: PMC11927653 DOI: 10.1097/txd.0000000000001768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 12/19/2024] [Indexed: 03/25/2025] Open
Abstract
Background Hypothermic machine perfusion (HMP) has greatly improved kidney allograft preservation. However, tissue damage still occurs during HMP, affecting posttransplant graft function. Therefore, better methods are needed to continuously assess organ quality and to predict posttransplant graft function and survival. We propose that soluble DNA (sDNA) concentration in HMP perfusate can be used as a noninvasive biomarker for this purpose. Methods Perfusate samples of kidney grafts placed on HMP were collected 5 min after the initiation of HMP and again at the conclusion of HMP. sDNA of nuclear origin from the perfusate was quantified by real-time polymerase chain reaction and correlated with HMP parameters and posttransplant clinical outcomes. Results Kidney grafts from 52 deceased donors placed on HMP were studied. Perfusate sDNA concentration was significantly higher in transplanted kidneys with delayed graft function. Higher concentrations of perfusate sDNA at 5 min and at HMP conclusion were also correlated with lower graft function in the initial posttransplant period, as measured by postoperative day 2, 3, and 4 creatinine reduction ratios. Standard pump parameters such as renal vascular resistance and renal vascular flow were poor indicators of early posttransplant graft function. Conclusions sDNA concentration in HMP perfusate of kidney grafts can indicate the quality of kidney graft preservation and predict posttransplant renal function. This biomarker should be explored further to improve renal organ assessment and transplantation outcomes.
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Affiliation(s)
- Sergio Duarte
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Anne-Marie Fassler
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Matthew Willman
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Duncan Lewis
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Curtis Warren
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Isabella Angeli-Pahim
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Rushi Shah
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Georgios Vrakas
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Ashraf El Hinnawi
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Werviston De Faria
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Thiago Beduschi
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Narendra Battula
- Division of Transplant Surgery, Department of Surgery, Oklahoma University College of Medicine, Oklahoma City, OK
| | - Ali Zarrinpar
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
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Kumar D, Yakubu I, Gupta G. Belatacept Versus Tacrolimus for Kidney Transplant Recipients of Deceased Donors With Acute Kidney Injury: Glass Half-Full? Transplantation 2025; 109:582-583. [PMID: 39348669 DOI: 10.1097/tp.0000000000005248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Affiliation(s)
- Dhiren Kumar
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA
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Madhusoodanan T, Schladt DP, Lyden GR, Lozano C, Miller JM, Pyke J, Weaver T, Israni AK, McKinney WT. Access to Transplant for African American and Latino Patients Under the 2014 US Kidney Allocation System. Transplantation 2025:00007890-990000000-01026. [PMID: 40064639 DOI: 10.1097/tp.0000000000005360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
BACKGROUND Kidney transplant offers better outcomes and reduced costs compared with chronic dialysis. However, racial and ethnic disparities in access to kidney transplant persist despite efforts to expand access to transplant and improve the equity of deceased donor allocation. Our objective was to evaluate after listing the association of race and ethnicity with access to deceased donor kidney transplant (DDKT) after changes to the allocation system in 2014. METHODS This retrospective study evaluated access to DDKT after listing since the implementation of the 2014 kidney allocation system. Waitlist status and transplant outcomes were ascertained from data from the Scientific Registry of Transplant Recipients. Our analysis included every adult kidney transplant candidate on the waiting list in the US from January 1, 2015, through June 30, 2023. RESULTS A total of 290 763 candidates were on the waiting list for DDKT during the study period. Of these, 36.4% of candidates were African American and 22.2% were Latino. Compared with White non-Latino patients, access to DDKT after listing was reduced for African American (unadjusted hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.92-0.94) and Latino individuals (unadjusted HR, 0.88; 95% CI, 0.87-0.90). After controlling for demographic and clinical factors, these differences in access to transplant widened substantially for African American (HR, 0.78; 95% CI, 0.77-0.80) and Latino patients (HR, 0.73; 95% CI, 0.72-0.74). CONCLUSIONS African American and Latino patients had reduced access to DDKT after listing. More effective approaches to improving access for African American and Latino individuals after listing are needed.
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Affiliation(s)
- Teija Madhusoodanan
- Nephrology Division, Hennepin Healthcare, Minneapolis, MN
- Department of Medicine, University of Minnesota, Minneapolis, MN
| | - David P Schladt
- Chronic Disease Research Group (CDRG), Minneapolis, MN
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
| | - Grace R Lyden
- Chronic Disease Research Group (CDRG), Minneapolis, MN
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
| | - Cinthia Lozano
- Division of Nephrology, Department of Medicine, University of Texas Medical Branch, Galveston, TX
| | - Jonathan M Miller
- Chronic Disease Research Group (CDRG), Minneapolis, MN
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
| | - Joshua Pyke
- Chronic Disease Research Group (CDRG), Minneapolis, MN
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
| | - Tim Weaver
- Chronic Disease Research Group (CDRG), Minneapolis, MN
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
| | - Ajay K Israni
- Division of Nephrology, Department of Medicine, University of Texas Medical Branch, Galveston, TX
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Warren T McKinney
- Scientific Registry of Transplant Recipients (SRTR), Minneapolis, MN
- Nephrology Division, Hennepin Healthcare Research Institute (HHRI), Minneapolis, MN
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12
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Khan MA, Hanna A, Sridhara S, Chaudhari H, Me HM, Attieh RM, Abu Jawdeh BG. Maintenance Immunosuppression in Kidney Transplantation: A Review of the Current Status and Future Directions. J Clin Med 2025; 14:1821. [PMID: 40142628 PMCID: PMC11943253 DOI: 10.3390/jcm14061821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Kidney transplantation remains the gold standard for managing end-stage kidney disease, providing superior survival and quality-of-life outcomes compared to dialysis. Despite the ongoing gap between organ availability and demand, it is inevitable that kidney transplantation will continue to grow. This is owed to broader organ sharing, increased comfort of transplant programs with marginal kidney utilization, and the expansion of paired exchange among living donor kidneys. The evolution of kidney transplantation could not have been possible without the availability of effective immunosuppressive regimens that prevent rejection and maintain graft function. Mycophenolic acid and calcineurin inhibitors continue to serve as the foundation of modern maintenance immunosuppression. While these agents have markedly reduced acute rejection rates, their long-term efficacy in graft survival remains suboptimal. Alternative immunosuppressive therapies, including belatacept and mammalian target of rapamycin inhibitors, have demonstrated potential benefits. However, concerns regarding an increased risk of rejection have limited their widespread adoption as primary treatment options. In addition to ongoing efforts to refine steroid- and calcineurin inhibitor-sparing strategies, the identification of practical and quantifiable biomarkers for predicting long-term graft survival remains a critical objective. This review evaluates contemporary immunosuppressive protocols, highlights existing challenges, and explores future directions for optimizing long-term transplant outcomes.
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Affiliation(s)
- Muhammad Ali Khan
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Alessandra Hanna
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Srilekha Sridhara
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Harshad Chaudhari
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Hay Me Me
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Rose Mary Attieh
- Department of Transplant, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Bassam G. Abu Jawdeh
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
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13
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Caldwell JS, Cheng XS, Chertow GM, Goldhaber-Fiebert JD. Kidney Transplant Wait Times Under Waiting List Expansion Scenarios. JAMA Netw Open 2025; 8:e251665. [PMID: 40126479 PMCID: PMC11933994 DOI: 10.1001/jamanetworkopen.2025.1665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 12/04/2024] [Indexed: 03/25/2025] Open
Abstract
Importance Kidney transplantation offers survival benefits and superior quality of life compared with maintenance dialysis for patients with end-stage kidney disease (ESKD), but it is limited to approximately 25 000 patients annually in the United States. Expanding access to transplant could be accomplished by allowing more patients to join the waiting list or by increasing organ supply. Objective To estimate how these interventions could affect transplant wait times. Design, Setting, and Participants This decision-analytic study used a Markov model with a simulated cohort of transplant-eligible US patients over 10 years (2022-2032). Exposures Three expansion strategies: waiting list expansion alone, waiting list expansion with deceased-donor transplant (DDT) expansion, and waiting list expansion with living-donor transplant (LDT) expansion. Relative 10%, 25%, 50%, and 100% expansions of the current deceased-donor organ supply and 25%, 50%, 100%, and 200% expansions of current living donation rates were simulated, modeling 2 degrees of waiting list expansion (10% and 50%) for each strategy. Main Outcomes and Measures Median wait time to kidney transplant using Kaplan-Meier survival analysis. Results There were a total of 662 190 transplant-eligible patients in the simulated cohort, with a mean (SD) age of 58.7 (14.7) years; 327 126 (49%) female individuals; and 269 082 (41%) Black, 163 028 (25%) Hispanic, 233 739 (35%) non-Hispanic White, and 78 496 (12%) Asian individuals and individuals with another race or ethnicity. Under the baseline strategy, median (IQR) wait time was 32.8 (13.1-66.4) months and increased to 36.8 (14.7-74.7) months and 52.6 (21.0-107.9) months for 10% and 50% waiting list expansion alone. DDT and LDT expansion strategies added 1911 to 20 035 organs. For 10% waiting list expansion, median (IQR) wait times ranged from 23.7 (9.3-47.8) months to 34.5 (13.9-74.7) months. For 50% waiting list expansion, median (IQR) wait times ranged from 34.2 (13.6-69.4) months to 49.4 (19.7-101.0) months. Conclusions and Relevance In this decision-analytic model, expansion strategies without additional organ supply increased the median time to kidney transplant by nearly 2 years; 10% waiting list expansion required at least 2850 additional organs to shorten wait times. However, 50% waiting list expansion required at least 11 000 additional organs to approximate current wait times. Reduction in the deceased-donor organ nonuse rate alone is unlikely to meet the shortfall. Systems-level efforts to significantly increase deceased and living donation should be prioritized alongside increased access to the transplant waiting list.
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Affiliation(s)
- Jillian S. Caldwell
- School of Medicine, Division of Nephrology, Stanford University, Stanford, California
| | - Xingxing S. Cheng
- School of Medicine, Division of Nephrology, Stanford University, Stanford, California
| | - Glenn M. Chertow
- School of Medicine, Division of Nephrology, Stanford University, Stanford, California
- Department of Health Policy, Stanford University, Stanford, California
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14
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Magua W, Cristea O, Eichenberger EM, Karadkhele GM, Morris AA, Newell K, Rickert JB, Larsen CP. Early Post-Transplant Renal Recovery Trajectory and Trajectory Velocity Functions Are Predictors of Estimated GFR at 1 Year: A Functional Data Analysis Approach. Clin Transplant 2025; 39:e70119. [PMID: 40047136 DOI: 10.1111/ctr.70119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 02/13/2025] [Accepted: 02/15/2025] [Indexed: 05/13/2025]
Abstract
INTRODUCTION Kidney function at 1-year post-transplant is an indicator of long-term graft function. Using functional data analysis (FDA), we evaluate the relationship between early renal recovery trajectories and kidney function at 1 year. METHODS We analyzed 1748 adults who underwent deceased-donor kidney transplantation between 2010 and 2021. Renal recovery trajectory functions were derived from longitudinal inverse creatinine values. Functional linear regression models were used to evaluate how well early (<90 days) renal recovery trajectory functions, and their rate of change explained 1-year eGFR. The explanatory power of the functional regression models was compared to results from ordinary least squares models, which used cross-sectional inverse creatinine values and linear slopes. Models were adjusted for age, sex, kidney donor profile index (KDPI), delayed graft function (DGF), race, body mass index (BMI), rejection, diabetes, hypertension, cytomegalovirus (CMV) serostatus risk, index admission length of stay, and immunosuppression agent. The R2 coefficient quantified the 1-year eGFR variation explained by model variables. RESULTS Adjusted functional linear models with renal recovery trajectory and trajectory velocity functions as independent variables explained 68% (65, 71), 70% (67, 74), 70% (66, 74), 70% (66, 75), and 73% (69, 79) of the variation in 1-year eGFR by 7, 14, 30, 60, and 90 days, respectively. By comparison, the ordinary least squares linear models explained a maximum of 69% of the variation in 1-year eGFR at 90 days. CONCLUSION Renal recovery patterns captured as continuous functions as early as 14 days are predictive of renal function at 1 year and may enable early personalized care of recipients at increased risk of poor graft function.
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Affiliation(s)
- Wairimu Magua
- Division of Transplantation, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Octav Cristea
- Division of Transplantation, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Emily M Eichenberger
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia, USA
| | - Geeta M Karadkhele
- Division of Transplantation, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Alanna A Morris
- Department of Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA
| | - Kenneth Newell
- Division of Transplantation, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | | | - Christian P Larsen
- Division of Transplantation, Department of Surgery, Emory University, Atlanta, Georgia, USA
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15
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Gu L, Gross AC, Kizilbash S. Multidisciplinary approach to optimizing long-term outcomes in pediatric kidney transplant recipients: multifaceted needs, risk assessment strategies, and potential interventions. Pediatr Nephrol 2025; 40:661-673. [PMID: 39356298 DOI: 10.1007/s00467-024-06519-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/18/2024] [Accepted: 08/19/2024] [Indexed: 10/03/2024]
Abstract
The post-transplant course of pediatric kidney transplant recipients is marked by a myriad of challenges, encompassing medical complications, recurrent hospitalizations, physical and dietary restrictions, and mental health concerns such as depression, anxiety, and post-traumatic stress disorder. Moreover, pediatric recipients are at risk of neurodevelopmental impairment, which may result in neurocognitive deficits and pose significant psychosocial obstacles. Addressing these multifaceted demands necessitates a multidisciplinary approach to pediatric kidney transplant care. However, the existing literature on the effective implementation of such a model remains scarce. This review examines the psychosocial and neurodevelopmental challenges faced by pediatric kidney transplant recipients and their families, discussing their impact on long-term transplant outcomes. Furthermore, it provides insights into risk assessment strategies and potential interventions within a multidisciplinary framework, aiming to enhance patient care and optimize post-transplant outcomes.
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Affiliation(s)
- Lidan Gu
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Amy C Gross
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Sarah Kizilbash
- Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave, MB680, Minneapolis, MN, 55454, USA.
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16
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Khairallah P, Lorenz EC, Waterman A, Aggarwal N, Pai A, Winkelmayer WC, Niu J. Trends in Kidney Allograft Failure Among First-Time Transplant Recipients in the United States. Am J Kidney Dis 2025; 85:273-283.e1. [PMID: 39521400 DOI: 10.1053/j.ajkd.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/28/2024] [Accepted: 09/17/2024] [Indexed: 11/16/2024]
Abstract
RATIONALE & OBJECTIVE The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019. EXPOSURE The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019. OUTCOME (1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure. ANALYTICAL APPROACH Competing risk survival analyses with the approach described by Fine and Gray used for the outcomes of waitlisting and retransplantation, and Cox proportional hazards models used for the outcome of all-cause mortality. RESULTS The absolute number of patients whose allograft failed and who started dialysis increased from 3,197 in 1990 to 5,821 in 2019. Compared with 1990-1994, the rate of waitlisting for a second transplant increased with each subsequent 5-year period, peaking between 2005 and 2009 before decreasing again subsequently. The rate of retransplantation following allograft failure decreased by 9%, 14%, 18%, 7%, and 11% in the sequential 5-year eras; and the mortality rate was 25% lower in 2015-2019 (HR, 0.75 [95% CI, 0.72-0.77]) compared with 1990-1994. Women had a reduced rate of waitlisting (HR, 0.93 [95% CI, 0.91-0.95]) and lower rate of retransplantation (HR, 0.93 [95% CI, 0.91-0.95]) compared with men. Compared with White patients, African American and Hispanic patients had significantly lower rates of waitlisting, retransplantation, and mortality. LIMITATIONS Retrospective data that lacks granular clinical information. CONCLUSIONS During the past 3 decades, among patients whose first kidney allograft failed and subsequently initiated dialysis, the rates of waitlisting for retransplantation increased while the rates of retransplantation and mortality decreased. Disparities based on race, ethnicity, and sex in waitlisting and retransplantation were observed and warrant further investigation. PLAIN-LANGUAGE SUMMARY Kidney allograft failure constitutes the fourth most common cause of dialysis initiation in the United States, and it accounts for 4% to 10% of yearly new dialysis starts globally. Little is known about the trends in the outcomes of patients whose kidney allograft failed. We studied US patients whose first kidney allograft failed between 1990 and 2019 to understand trends in waitlisting for retransplantation, retransplantation, and all-cause mortality after kidney allograft failure. Among patients whose first kidney allograft failed and started dialysis, rates of waitlisting increased and rates of retransplantation and mortality decreased over the past 3 decades. We found racial, ethnic, and sex-based disparities in outcomes. Compared with White patients, African American and Hispanic patients had significantly lower rates of waitlisting, retransplantation, and mortality. Women also had lower rates of waitlisting and retransplantation compared with men.
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Affiliation(s)
| | | | - Amy Waterman
- Department of Surgery and J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas
| | - Nidhi Aggarwal
- Section of Nephrology, Baylor College of Medicine, Houston, Texas
| | - Akshta Pai
- Section of Nephrology, Baylor College of Medicine, Houston, Texas
| | | | - Jingbo Niu
- Section of Nephrology, Baylor College of Medicine, Houston, Texas
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17
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Nielsen J, Chen X, Davis L, Waterman A, Gentili M. Investigating the Classification of Living Kidney Donation Experiences on Reddit and Understanding the Sensitivity of ChatGPT to Prompt Engineering: Content Analysis. JMIR AI 2025; 4:e57319. [PMID: 39918869 PMCID: PMC11845884 DOI: 10.2196/57319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 09/18/2024] [Accepted: 11/18/2024] [Indexed: 02/09/2025]
Abstract
BACKGROUND Living kidney donation (LKD), where individuals donate one kidney while alive, plays a critical role in increasing the number of kidneys available for those experiencing kidney failure. Previous studies show that many generous people are interested in becoming living donors; however, a huge gap exists between the number of patients on the waiting list and the number of living donors yearly. OBJECTIVE To bridge this gap, we aimed to investigate how to identify potential living donors from discussions on public social media forums so that educational interventions could later be directed to them. METHODS Using Reddit forums as an example, this study described the classification of Reddit content shared about LKD into three classes: (1) present (presently dealing with LKD personally), (2) past (dealt with LKD personally in the past), and (3) other (LKD general comments). An evaluation was conducted comparing a fine-tuned distilled version of the Bidirectional Encoder Representations from Transformers (BERT) model with inference using GPT-3.5 (ChatGPT). To systematically evaluate ChatGPT's sensitivity to distinguishing between the 3 prompt categories, we used a comprehensive prompt engineering strategy encompassing a full factorial analysis in 48 runs. A novel prompt engineering approach, dialogue until classification consensus, was introduced to simulate a deliberation between 2 domain experts until a consensus on classification was achieved. RESULTS BERT and GPT-3.5 exhibited classification accuracies of approximately 75% and 78%, respectively. Recognizing the inherent ambiguity between classes, a post hoc analysis of incorrect predictions revealed sensible reasoning and acceptable errors in the predictive models. Considering these acceptable mismatched predictions, the accuracy improved to 89.3% for BERT and 90.7% for GPT-3.5. CONCLUSIONS Large language models, such as GPT-3.5, are highly capable of detecting and categorizing LKD-targeted content on social media forums. They are sensitive to instructions, and the introduced dialogue until classification consensus method exhibited superior performance over stand-alone reasoning, highlighting the merit in advancing prompt engineering methodologies. The models can produce appropriate contextual reasoning, even when final conclusions differ from their human counterparts.
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Affiliation(s)
- Joshua Nielsen
- Department of Industrial Engineering, JB Speed School of Engineering, University of Louisville, Louisville, KY, United States
| | - Xiaoyu Chen
- Department of Industrial and Systems Engineering, School of Engineering and Applied Sciences, University at Buffalo, Buffalo, NY, United States
| | - LaShara Davis
- Patient Engagement, Diversity, and Education Division, Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
| | - Amy Waterman
- Patient Engagement, Diversity, and Education Division, Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
| | - Monica Gentili
- Department of Industrial Engineering, JB Speed School of Engineering, University of Louisville, Louisville, KY, United States
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18
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Papa S, Popovic A, Hod Dvorai R, Shahbazov R. The Impact of Learning Curve on Robotic Living Donor Nephrectomy Outcomes: Retrospective Analysis. Int J Med Robot 2025; 21:e70041. [PMID: 39835438 DOI: 10.1002/rcs.70041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 12/22/2024] [Accepted: 01/09/2025] [Indexed: 01/22/2025]
Abstract
BACKGROUND We aimed to investigate the outcome of patients after RDN at different time points. METHODS We studied the outcomes of 77 living robotic living donor nephrectomies (RDN). Donors were separated into three groups: learning curve period (LCP), stabilisation period (SP), and teaching period (TP). RESULTS There were significant differences in blood loss and hospitalisation times between the three groups. Operative time was significantly shorter in the LCP group compared with the SP and TP groups (282 ± 51.6 min vs. 308 ± 38.7 min vs. 314 ± 28.7, p = 0.02). However, warm ischaemia time was shorter in the TP group compared with the LCP and SP groups (5.0 ± 3.6 min vs. 3.4 ± 3.2 min vs. 1.5 ± 1.3 min, p < 0.01). Complication rates were higher in the LCP group compared with the SP and TP groups (p = 0.04). CONCLUSION This study demonstrated that RDN outcomes improve after the learning period.
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Affiliation(s)
- Sarah Papa
- Department of Surgery, Division of Transplantation, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Aleksandar Popovic
- Department of Surgery, Division of Urology, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Reut Hod Dvorai
- Department of Pathology and Laboratory Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Rauf Shahbazov
- Department of Surgery, Division of Transplantation, SUNY Upstate Medical University, Syracuse, New York, USA
- Department of Surgery, Division of Transplantation, Albany Medical Center, Albany, New York, USA
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19
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Peticca B, Khalil IY, Robinson SG, Prudencio TM, Inlaw C, Majeethia H, Di Carlo A, Karhadkar SS. Underappreciated Effects of Delayed Graft Function in Pediatric Kidney Transplantation. Pediatr Transplant 2025; 29:e14901. [PMID: 39688245 DOI: 10.1111/petr.14901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/10/2024] [Accepted: 11/12/2024] [Indexed: 12/18/2024]
Abstract
PURPOSE In kidney transplantation (KT), delayed graft function (DGF) is associated with worse outcomes. However, it is unclear what effect DGF plays in long-term survival compared to the impact of the various transplant, donor, and recipient risk factors associated with DGF. This study aims to determine the effect of DGF alone on long-term survival in pediatric deceased donor kidney transplant recipients (DDKTRs). METHODS Using a national database, 1728 pediatric patients who received a kidney transplant between 1994 and 2009 (n = 978) and 2010 and 2022 (n = 750) were identified. Cases and controls were matched by DGF status for transplant date, cold ischemia time, distance from the transplant center, HLA mismatch level, PRA, KDPI, recipient and donor age, BMI, sex assigned at birth, and ethnicity. Kaplan-Meier curves were analyzed with a log-rank test. Pearson's chi-squared tests were used to compare survival proportions between groups at time benchmarks. RESULTS Pediatric DDKTRs with DGF had worse graft (p < 0.001) and patient (p < 0.001) survival compared to non-DGF patients in both eras. Between 1994 and 2009, graft survival rates were lower in the DGF cohort at 1 (p < 0.001), 3 (p < 0.001), 5 (p < 0.001), and 10 years (p = 0.010). Patient survival rates were lower in the DGF cohort at 1 (p = 0.017) and 5 years (p = 0.019) post-DDKT. There was no difference in 3 (p = 0.071) and 10-year patient survival rates (p = 0.141). Between 2010 and 2022, graft and patient survival rates were lower in the DGF cohort at 1, 3, 5, and 10 years (all p < 0.001). There was no difference in rates of retransplantation (p = 0.307 and p = 0.771) between groups for either era. CONCLUSIONS DGF alone is associated with worse outcomes in pediatric DDKTRs. DGF should be taken seriously, especially in cases where pediatric DDKTRs do not possess known, attributable risk factors for DGF.
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Affiliation(s)
- Benjamin Peticca
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Ibrahim Y Khalil
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Samuel G Robinson
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Tomas M Prudencio
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Christopher Inlaw
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Heli Majeethia
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Antonio Di Carlo
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania, USA
| | - Sunil S Karhadkar
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania, USA
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20
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Anwar IJ, DeLaura I, Ladowski JM, Schilirò D, Gao Q, Manook M, Yoon J, Belloni R, Park A, Schuster DJ, Song M, Lin L, Farris AB, Magnani D, Williams K, Kwun J, Knechtle SJ. CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients. Sci Transl Med 2025; 17:eadn8130. [PMID: 39742504 PMCID: PMC11797747 DOI: 10.1126/scitranslmed.adn8130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 12/05/2024] [Indexed: 01/03/2025]
Abstract
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells. After transplant, the nonhuman primates maintained on 5C8-based immunosuppression had significantly better survival compared with those maintained on SOC immunosuppression (135.2 days versus 32.8 days, P = 0.013). The 5C8-treated group demonstrated better suppression of DSAs after transplant, more robust suppression of B cell populations, and better induction of regulatory T cells. Fewer infectious and welfare complications, including viral reactivation and weight loss, were also observed with 5C8-based immunosuppression compared with SOC immunosuppression. Therefore, anti-CD154 mAbs may improve kidney transplant outcomes through better control of posttransplant immune responses. The superior efficacy of anti-CD154 mAb-based immunosuppression over tacrolimus-based SOC seen in this highly sensitized NHP transplant model suggests that anti-CD154 mAbs could potentially be used to desensitize and treat highly sensitized patients receiving kidney transplantation.
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Affiliation(s)
- Imran J. Anwar
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Isabel DeLaura
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Joseph M. Ladowski
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Davide Schilirò
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Qimeng Gao
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Miriam Manook
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Janghoon Yoon
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Rafaela Belloni
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Angela Park
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Daniel J. Schuster
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Mingqing Song
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Lin Lin
- Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA
| | - Alton B. Farris
- Department of Pathology, Emory University School of Medicine; Atlanta, GA 30322, USA
| | - Diogo Magnani
- Nonhuman Primate reagent Resource, UMass Chan Medical School, Worcester, MA 01605, USA
| | - Kyha Williams
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Jean Kwun
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Stuart J. Knechtle
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
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21
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Wang J, Zhou T. Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety. Med Res Rev 2025; 45:311-343. [PMID: 39180410 DOI: 10.1002/med.22077] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 07/20/2024] [Accepted: 08/04/2024] [Indexed: 08/26/2024]
Abstract
Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.
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Affiliation(s)
- Jinyi Wang
- Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, China
- Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Tingting Zhou
- Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, China
- Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai, China
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22
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Gu L, Anzalone CJ, Kane-Grade F, Glad D, Evans M, Kizilbash S. Neurocognitive disruption in pediatric kidney transplant candidates: Medical and sociodemographic factors. APPLIED NEUROPSYCHOLOGY. CHILD 2024:1-10. [PMID: 39632247 DOI: 10.1080/21622965.2024.2436599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
We evaluated the effects of kidney failure etiology, dialysis, and area deprivation index on the subdomains of neurocognitive functioning in pediatric kidney transplant candidates. The study included 78 pediatric kidney transplant candidates (47.4% male, 70.5% White, M.age = 11.77 years, and 51.3% patients have public insurance) who completed a pre-transplant neuropsychological evaluation between 1/1/2010 and 10/31/2022. Linear regression models were employed to complete data analyses. The mean scores of various neurocognitive functioning domains in pediatric kidney transplant candidates were significantly lower than in the general population (ps < .001). After adjusting for covariates, patients with congenital anomalies of the kidney and urinary tract (M = 87; 95% CI: 80-94) and other etiologies (M = 82; 95% CI: 76-89) had significantly lower processing speed compared to patients with nephrotic syndrome (M = 98; 95% CI: 89-107) (p = .02). Patients living in high-level deprivation neighborhoods showed significantly lower verbal skills (p = .01), working memory performance (p = .02), and full-scale IQ (p = .03) than patients living in median-level and low-level deprivation neighborhoods. Additionally, dialysis did not show significant association with neurocognitive domains ((ps ranged from .07 to .52).
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Affiliation(s)
- Lidan Gu
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Christopher J Anzalone
- Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Harvard Medical School
| | - Finola Kane-Grade
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Danielle Glad
- Division of Neuropsychology, Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Michael Evans
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, United States
| | - Sarah Kizilbash
- Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States
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23
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Syed FJ, Bekbolsynov D, Green RC, Kaur D, Ekwenna O, Sindhwani P, Rees M, Stepkowski S. Potential of new 250-nautical mile concentric circle allocation system for improving the donor/recipient HLA matching: Development of new matching algorithm. Transpl Immunol 2024; 87:102146. [PMID: 39537113 DOI: 10.1016/j.trim.2024.102146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 11/06/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND High-resolution typing of human leukocyte antigen (HLA) may revolutionize the field of kidney transplantation by selection of low immunogenic grafts. The new 250-nautical mile circle allocation system offers a unique opportunity to find low HLA immunogenic donors for eligible recipients. METHODS 501 transplant candidates from the University of Toledo Medical Center (UTMC) between 2015 and 2019, registered at the Scientific Registry of Transplant Recipients (SRTR) were virtually matched to 4812 donors procured within 250-nautical miles using an in-house-developed simulation algorithm. Immunogenicity of HMS (hydrophobic mismatch score) ≤10 was measured based on imputed high-resolution HLAs. Simulated "optimal" matches with a KDPI≤50 % were compared with the transplant cohort between 2000 and 2010 with their kidney allograft survivals. RESULTS Out of 501 recipients 500 (99.8 %) were matched with donors ≤10 HMS and KDPI ≤50 %. The average HMS value for simulated transplants was 1.4 (range 0-10) versus 6.3 (range 0-75) in the retrospective cohort (p < 0.001). The simulated model had a median mismatch number of 3/6, while the reference cohort 4/6 among HLA-A/B/DR antigens (p < 0.001). The estimated median graft survival was 18.2 years for the simulated cohort vs. 13.4 years in the real-life cohort (p < 0.001), gaining 4.9 years per transplant and 2450 survival years for all patients. For year 2014, out of 98 patients and 659 donors, each recipient had a median number of 141 donors (HMS < 10; range 8-378). Similar values were found for patients between 2015 and 2019. CONCLUSION Donors within 250-nautical miles proffers excellent and multiple options for finding well-matched low immunogenic HLA kidney donors for UTMC patients, thus significantly improving their chances for long-term allograft survival.
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Affiliation(s)
- Fayeq Jeelani Syed
- Electrical Engineering and Computer Science Department, University of Toledo, 2801 W Bancroft St., Toledo 43606, OH, USA
| | - Dulat Bekbolsynov
- Department of Medical Microbiology and Immunology, University of Toledo Medical Center, 3000 Arlington Ave., Toledo 43614, OH, USA.
| | - Robert C Green
- Department of Computer Science, Bowling Green State University, 1001 E Wooster St., Bowling Green 43403, OH, USA
| | - Devinder Kaur
- Electrical Engineering and Computer Science Department, University of Toledo, 2801 W Bancroft St., Toledo 43606, OH, USA
| | - Obi Ekwenna
- Department of Urology, University of Toledo Medical Center, 3000 Arlington Ave., Toledo 43614, OH, USA
| | - Puneet Sindhwani
- Department of Urology, University of Toledo Medical Center, 3000 Arlington Ave., Toledo 43614, OH, USA
| | - Michael Rees
- Department of Urology, University of Toledo Medical Center, 3000 Arlington Ave., Toledo 43614, OH, USA
| | - Stanislaw Stepkowski
- Department of Medical Microbiology and Immunology, University of Toledo Medical Center, 3000 Arlington Ave., Toledo 43614, OH, USA
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24
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Ammar M, Yaich S, Hakim A, Ghozzi H, Sahnoun Z, Ben Hmida M, Zghal K, Ben Mahmoud L. Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients. Ren Fail 2024; 46:2313863. [PMID: 38345031 PMCID: PMC10863538 DOI: 10.1080/0886022x.2024.2313863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND The effect of tacrolimus (TAC) on oxidative stress after kidney transplantation (KT) is unclear. This study aimed to evaluate the influence of TAC trough levels of oxidative stress status in Tunisian KT patients during the post-transplantation period (PTP). METHODS A prospective study including 90 KT patients was performed. TAC whole-blood concentrations were measured by the microparticle enzyme immunoassay method and adjusted according to the target range. Plasma levels of oxidants (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)) and antioxidants (ascorbic acid, glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured using spectrophotometry. The subjects were subdivided according to PTP into three groups: patients with early, intermediate, and late PT. According to the TAC level, they were subdivided into LL-TAC, NL-TAC, and HL-TAC groups. RESULTS A decrease in MDA levels, SOD activity, and an increase in GSH levels and GPx activity were observed in patients with late PT compared to those with early and intermediate PT (p < 0.05). Patients with LL-TAC had lower MDA levels and higher GSH levels and GPx activity compared with the NL-TAC and HL-TAC groups (p < 0.05). CONCLUSION Our results have shown that in KT patients, despite the recovery of kidney function, the TAC reduced but did not normalize oxidative stress levels in long-term therapy, and the TAC effect significantly depends on the concentration used.
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Affiliation(s)
- Mariam Ammar
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
- Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia
| | - Soumaya Yaich
- Department of Nephrology, Hedi Chaker University Hospital, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Renal Pathology, University of Sfax, Sfax, Tunisia
| | - Ahmed Hakim
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
| | - Hanen Ghozzi
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
| | - Zouheir Sahnoun
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
| | - Mohamed Ben Hmida
- Department of Nephrology, Hedi Chaker University Hospital, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Renal Pathology, University of Sfax, Sfax, Tunisia
| | - Khaled Zghal
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
| | - Lobna Ben Mahmoud
- Department of Pharmacology, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Laboratory of Research of Pharmacology and Toxicology, University of Sfax, Sfax, Tunisia
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25
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Ye X, Lin Y, Yang J, Qi B, Wei X, Huang Y, Wang L. Deciphering the pathogen heterogeneity for precise diagnosis and personalized therapeutics of infections after kidney transplantation: insights from metagenomic next-generation sequencing. Front Cell Infect Microbiol 2024; 14:1456407. [PMID: 39611100 PMCID: PMC11602478 DOI: 10.3389/fcimb.2024.1456407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 10/28/2024] [Indexed: 11/30/2024] Open
Abstract
Introduction The aim of this study was to compare the detection performance of mNGS against that of conventional tests (CT) in patients suffering from infection after kidney transplantation. Methods A total of 138 samples from 85 kidney transplant patients with acute or chronic infections were simultaneously analyzed using mNGS and CT from July 2021 to August 2023. Results Compared with CT, mNGS demonstrated a higher sensitivity (95.96% vs. 27.27%) but lower specificity (48.72% vs. 84.62%) in pathogen detection. Moreover, mNGS exhibited significant advantages in detecting mixed and rare infections. The pathogens commonly identified in kidney transplant patients were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), followed by Pneumocystis jirovecii and Cytomegalovirus (CMV). mNGS guided the precise clinical diagnosis in 89.13% of cases and assisted in altering therapeutics from empirical antibiotic approaches to personalized plans in 56.10% of cases, including treatment escalation (40.65%), initiation (11.38%), drug adjustment (3.25%), and de-escalation (0.81%). Discussion Our study demonstrated the superior detection performance of mNGS and its significant clinical value. This reflected the great potential of mNGS as a complementary clinical detection technology for kidney transplant patients.
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Affiliation(s)
- Xin Ye
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuxin Lin
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiangnan Yang
- Department of Medicine, Dinfectome Inc., Nanjing, China
| | - Baocui Qi
- Department of Medicine, Dinfectome Inc., Nanjing, China
| | - Xuedong Wei
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhua Huang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Liangliang Wang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Thompson A, Fleischmann KE, Smilowitz NR, de Las Fuentes L, Mukherjee D, Aggarwal NR, Ahmad FS, Allen RB, Altin SE, Auerbach A, Berger JS, Chow B, Dakik HA, Eisenstein EL, Gerhard-Herman M, Ghadimi K, Kachulis B, Leclerc J, Lee CS, Macaulay TE, Mates G, Merli GJ, Parwani P, Poole JE, Rich MW, Ruetzler K, Stain SC, Sweitzer B, Talbot AW, Vallabhajosyula S, Whittle J, Williams KA. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2024; 150:e351-e442. [PMID: 39316661 DOI: 10.1161/cir.0000000000001285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
AIM The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.
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Affiliation(s)
| | | | | | - Lisa de Las Fuentes
- Former ACC/AHA Joint Committee on Clinical Practice Guidelines member; current member during the writing effort
| | | | | | | | | | | | | | | | - Benjamin Chow
- Society of Cardiovascular Computed Tomography representative
| | | | | | | | | | | | | | | | | | | | | | - Purvi Parwani
- Society for Cardiovascular Magnetic Resonance representative
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27
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Thompson A, Fleischmann KE, Smilowitz NR, de Las Fuentes L, Mukherjee D, Aggarwal NR, Ahmad FS, Allen RB, Altin SE, Auerbach A, Berger JS, Chow B, Dakik HA, Eisenstein EL, Gerhard-Herman M, Ghadimi K, Kachulis B, Leclerc J, Lee CS, Macaulay TE, Mates G, Merli GJ, Parwani P, Poole JE, Rich MW, Ruetzler K, Stain SC, Sweitzer B, Talbot AW, Vallabhajosyula S, Whittle J, Williams KA. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2024; 84:1869-1969. [PMID: 39320289 DOI: 10.1016/j.jacc.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
AIM The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.
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28
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Gramkow AM, Baatrup JH, Gramkow ET, Koefoed-Nielsen P, Wittenhagen P, Thiesson HC. The Impact of Reduced Immunosuppression on Alloimmunity: A Retrospective Study of Pediatric Kidney Transplant Recipients. Pediatr Transplant 2024; 28:e14880. [PMID: 39462688 DOI: 10.1111/petr.14880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/12/2024] [Accepted: 10/13/2024] [Indexed: 10/29/2024]
Abstract
BACKGROUND Kidney transplantation is the best treatment for end-stage kidney disease but requires immunosuppressive medications, which have significant side effects. Many pediatric recipients experience these side effects, leading to dosage reductions, which potentially increase the risk of alloimmunity. We aimed to describe the alteration in immunosuppressive medication, explore the reasons for the reductions, and assess the potential impact on alloimmunity. METHOD Data from 49 pediatric kidney transplant recipients receiving an allograft from 2009 to 2020 were retrospectively studied. The recipients were screened for HLA antibodies after the transplantation. RESULTS The median age of recipients was 11 years (IQR 8), with a median follow-up of 5 years (IQR 5). Eighty percent of the transplantations were corticosteroid-free. During follow-up, 11% developed de novo donor-specific antibodies (dnDSA), and 60% had detectable HLA antibodies. The 1-year rejection rate was 4%. Immunosuppressive medication was altered substantially in most recipients, resulting in 72% being on mono- or dual therapy with a reduced mycophenolate mofetil (MMF) dosage by the end of the first posttransplant year. The median MMF dose was nearly half of the intended. Tacrolimus levels were maintained close to the target of 5 ng/mL. No association was found between reduced immunosuppression and dnDSA or rejections. Reductions were primarily due to MMF-related side effects: leukopenia in 77%, gastrointestinal issues in 34%, and infections with Epstein-Barr virus, cytomegalovirus, and BK polyomavirus in 49%. CONCLUSIONS Reduced MMF with a sufficient trough tacrolimus level in a population of mainly corticosteroid-free pediatric kidney transplant recipients did not lead to unacceptable alloimmunity.
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Affiliation(s)
- Ann-Maria Gramkow
- Department of Nephrology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Johanne H Baatrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Emilie T Gramkow
- Department of Nephrology, Odense University Hospital, Odense, Denmark
- Department of Molecular Medicine - Cancer and Inflammation, University of Southern Denmark, Odense, Denmark
| | | | - Per Wittenhagen
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Helle C Thiesson
- Department of Nephrology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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29
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Johnson JC, Malik M, Engebretsen TL, Mujtaba M, Lea AS, Stevenson HL, Kueht ML. Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database. Drugs Aging 2024; 41:915-927. [PMID: 39417973 DOI: 10.1007/s40266-024-01147-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. OBJECTIVE The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. METHODS The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥ 65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. RESULTS After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2 ± 3.7 years (ESW) and 69.2 ± 3.4 years (SCI, p = 0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p = 0.01) and 3 years (34.89% vs 44.29%, p = 0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p = 0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p = 0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p < 0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. CONCLUSIONS There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.
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Affiliation(s)
- John C Johnson
- John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77550, USA.
| | - Moosa Malik
- John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77550, USA
| | - Trine L Engebretsen
- Division of Multiorgan Transplant and Hepatobiliary Surgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA
| | - Muhammad Mujtaba
- Division of Transplant Nephrology, Department of Medicine, The University of Texas Medical Branch, Galveston, TX, USA
| | - A Scott Lea
- Division of Infectious Disease, Department of Medicine, The University of Texas Medical Branch, Galveston, TX, USA
| | - Heather L Stevenson
- Division of Transplant Pathology, Department of Pathology, The University of Texas Medical Branch, Galveston, TX, USA
| | - Michael L Kueht
- Division of Multiorgan Transplant and Hepatobiliary Surgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA
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30
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Ku E, Legaspi S, Copeland TP, Adey DB, Whelan AM, Roll GR, McCulloch CE, Lee BK, Johansen KL. Living Donor Candidates' Self-reported Health and Health Perceptions and Completion of Donor Evaluation: A Cohort Study. Kidney Med 2024; 6:100909. [PMID: 39534796 PMCID: PMC11554918 DOI: 10.1016/j.xkme.2024.100909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
Rationale & Objective Given the organ shortage in the United States, increasing living donation is vital to improving access to kidney transplantation, but many donor candidates do not complete the donor evaluation. Our objective was to understand potential living donors' perceived health and its association with the likelihood of completing the donor evaluation process. Study Design Potential donors' self-reported health was ascertained using the Patient Reported Outcomes Measurement Information System (PROMIS) global physical and mental health and the Davies and Ware Health Perceptions surveys. Setting & Participants Potential living donors who expressed interest in donation at a single medical center were recruited prospectively between 2017 and 2022. Exposure Donors' self-reported health and health perceptions. Outcomes Completion of the donor evaluation. Analytical Approach Adjusted linear and logistic regression models were used to examine the association between self-reported health and health perceptions with outcomes. Results A total of 1,347 individuals were included for study; 46% (N = 613) were < 40 years of age, 71% (n = 951) were female, 22% (n = 294) were of Hispanic ethnicity, and 16% (n = 215) completed the donor evaluation. The mean PROMIS global physical health (17.0 ± 1.9) and mental health (15.5 ± 2.7) raw scores were higher among donor candidates proceeding to completion of the donor evaluation when compared with those who withdrew early in the process (16.3 ± 2.2 for physical health and 14.9 ± 3.1 for mental health). Every z-score change in the PROMIS physical health score was associated with 1.48-fold higher odds of completing the donor evaluation (95% CI, 1.19-1.85). Fully adjusted models incorporating the PROMIS scores for predicting the completion of donor evaluations had a c-statistic of 0.70. Potential donors' Davies and Wares health perceptions did not predict the likelihood of completing the donor evaluation in fully adjusted models. Limitations Data are derived from a single center and may not generalize to the donor evaluation process at other transplant centers. Conclusions Donor candidates' self-reported physical health may serve as a predictor of the likelihood of completing the donor evaluation process and a potential avenue for future interventions.
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Affiliation(s)
- Elaine Ku
- Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Sabrina Legaspi
- Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California
| | - Timothy P. Copeland
- Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California
| | - Deborah B. Adey
- Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California
| | - Adrian M. Whelan
- Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California
| | - Garrett R. Roll
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, California
| | - Charles E. McCulloch
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Brian K. Lee
- Department of Medicine, Division of Nephrology, University of Texas, Austin
| | - Kirsten L. Johansen
- Hennepin Healthcare, Division of Nephrology, Department of Medicine, University of Minnesota, Minneapolis
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Hasan N, Zakhour R, Sanchez LHG, Lloyd AR, Li G, Ortiz CL, Hutto C. Post-Transplant Lymphoproliferative Disorder Presenting as a Gastrointestinal Fistulous Tract in a Heart Transplant Recipient: Case Report and Literature Review. Transplant Proc 2024; 56:2084-2091. [PMID: 39214719 DOI: 10.1016/j.transproceed.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 06/21/2024] [Accepted: 07/12/2024] [Indexed: 09/04/2024]
Abstract
We present a challenging case of Epstein-Barr virus-related isolated small bowel post-transplant lymphoproliferative disorder (PTLD) in a pediatric heart transplant recipient presenting as recurrent gastrointestinal (GI) bleeding and subsequently a GI fistulous tract with associated intra-abdominal abscess. Diagnosis was not confirmed until exploratory laparoscopy was performed, with excision of the fistulous tract revealing evidence of PTLD on pathology. Early diagnosis of GI-PTLD remains a challenge, especially if isolated in the small intestine. Diagnosis may rely on positron emission tomography/ computed tomography scan (PET/CT) or invasive intervention to obtain appropriate tissue samples for pathology diagnosis.
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Affiliation(s)
- Nour Hasan
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Saint Louis University, St. Louis, Missouri.
| | - Ramia Zakhour
- Division of Pediatric Infectious Diseases, Department of Pediatrics, McGovern Medical School at UTHealth, Houston, Texas; Children's Memorial Hermann Hospital, Houston, Texas
| | - Luz Helena Gutierrez Sanchez
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Alabama at Birmingham, Birmingham, Alabama; Children's of Alabama, Birmingham, Alabama
| | - Audrey R Lloyd
- Children's of Alabama, Birmingham, Alabama; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Geling Li
- Children's of Alabama, Birmingham, Alabama; Department of Pathology and Laboratory Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Clara L Ortiz
- Children's of Alabama, Birmingham, Alabama; Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Cecelia Hutto
- Children's of Alabama, Birmingham, Alabama; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
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Huang AA, Zahid JO, Haji M, Ansari I, Singh M, Dietch Z, Desai A, Ho B, Friedewald JJ, Rohan V. Association of Pre-Existing Type 2 Diabetes on Kidney Transplant Outcomes and Factors Correlating With Survival: A Single-Center Analysis. J Surg Res 2024; 303:268-274. [PMID: 39388991 DOI: 10.1016/j.jss.2024.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 08/07/2024] [Accepted: 09/08/2024] [Indexed: 10/12/2024]
Abstract
INTRODUCTION Kidney transplantation (KT) is the treatment of choice for end-stage renal disease. Diabetes mellitus is the most common indication for KT, with most recipients having type 2 diabetes mellitus (T2DM). Previous studies have shown inferior patient survival in T2DM KT recipients. This single-center study aimed to understand the individual factors associated with negative long-term outcomes. METHODS This is a single-center retrospective analysis of adult KT recipients, with and without T2DM from 2012 to 2017 with a follow-up through December 2022. Primary Outcomes were graft loss and patient survival. Univariate, Multivariate Cox regression, and Kaplan-Meier analyses were used to assess KT outcomes. RESULTS We analyzed 1185 patients, 288 (24.3%) with T2DM. T2DM patients tended to be older, 56.6 ± 9.8 versus 47.1 ± 13.7 y. (P < 0.01), male (66.3% versus 58.2% P < 0.001) had a higher body mass index, 31.3 ± 5.4 versus 27.4 ± 5.7 P < 0.01) and less likely to get a living donor transplant (46.5% versus 58.4%, P < 0.01). T2DM patients after KT had a 50% higher risk for graft loss (hazard ratio 1.509, 95% CI 1.15-1.95, P < 0.001) and a 106% higher risk of death (hazard ratio 2.06 (95% CI 1.48-2.87, P < 0.0001). Among the T2DM patients, the most common cause of death was infection (39.9%). The average HbA1c at 1 y after transplant was 7.8%. CONCLUSIONS The present study shows that T2DM is strongly associated with an increased risk of graft loss and death after KT, particularly in older recipients of deceased donor transplants with longer cold ischemia time that experience delayed graft function. This underscores the importance of avoiding delayed graft function in older, type 2 diabetic kidney transplant recipients and prioritizing living donors.
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Affiliation(s)
- Alexander A Huang
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Jasmine O Zahid
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Maaz Haji
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Ismail Ansari
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Manasi Singh
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Zachary Dietch
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Amishi Desai
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Bing Ho
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - John J Friedewald
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois
| | - Vinayak Rohan
- Northwestern Medicine Organ Transplantation Center, Chicago, Illinois.
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Yabuuchi K, Horinouchi T, Yamamura T, Nozu K, Takasato M. Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived iPSCs. Genes Cells 2024. [PMID: 39435529 DOI: 10.1111/gtc.13170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/13/2024] [Accepted: 09/17/2024] [Indexed: 10/23/2024]
Abstract
Alport syndrome (AS) is a hereditary disease caused by mutations in the COL4A5 gene and leads to chronic kidney disease. Currently, no specific treatment has been developed. However, a recent study using AS-model mice demonstrated that the exon skipping method could partially rescue the symptoms. In this study, we evaluated the effects of the exon skipping method using kidney organoids generated from AS-patient-derived induced pluripotent stem cells (AS-iPSCs). We generated kidney organoids from AS-iPSCs, which exhibited nephron structures. As expected, the C-terminus of COL4A5 was not expressed in AS-organoids. Interestingly, anti-sense oligonucleotides restored the expression of the C-terminus of COL4A5 in vitro. Next, we transplanted AS-organoids into mice and evaluated glomerular basement membrane formation in vivo. We found that AS-organoids formed a lower slit diaphragm ratio compared to control organoids. Finally, we assessed the effects of exon skipping on transplanted organoids but observed minimum effects. These studies suggest that AS-iPSCs can generate kidney organoids lacking the C-terminus of COL4A5, and that exon skipping can induce its expression in vitro.
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Affiliation(s)
- Kensuke Yabuuchi
- Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
- Department of Development and Regeneration, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Tomoko Horinouchi
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomohiko Yamamura
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kandai Nozu
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Minoru Takasato
- Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
- Department of Development and Regeneration, Graduate School of Medicine, Osaka University, Suita, Japan
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Overstreet M, Culpepper H, DeHoff D, Gebregziabher M, Posadas Salas MA, Su Z, Chandler J, Bartlett F, Dunton P, Carcella T, Taber D. Multifaceted Intervention to Improve Graft Outcome Disparities in African American Kidney Transplants (MITIGAAT Study): Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2024; 13:e57784. [PMID: 39388231 PMCID: PMC11502971 DOI: 10.2196/57784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/13/2024] [Accepted: 06/26/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND The outcome disparities for African American recipients of kidney transplant is a public health issue that has plagued the field of transplant since its inception. Based on national data, African American recipients have nearly twice the risk of graft loss at 5 years after transplant, when compared with White recipients. Evidence demonstrates that medication nonadherence and high tacrolimus variability substantially impact graft outcomes and racial disparities, most notably late (>2 years) after the transplant. Nonadherence is a leading cause of graft loss. Prospective multicenter data demonstrate that one-third of all graft loss are directly attributed to nonadherence. We have spent 10 years of focused research to develop a comprehensive model explaining the predominant risk factors leading to disparities in African American kidney recipients. However, there are still gaps in patient-level data that hinder the deeper understanding of the disparities. Lack of data from the patient often lead to provider biases, which will be addressed with this intervention. Culturally competent, pharmacist-led interventions in medication therapy management will also address therapeutic inertia. Pharmacist interventions will mitigate medication access barriers as well (cost and insurance denials). Thus, this multidimensional intervention addresses patient, provider, and structural factors that drive racial disparities in African American kidney recipients. OBJECTIVE This prospective, randomized controlled trial aimed to determine the impact of multimodal health services intervention on health outcomes disparities in African American recipients of kidney transplant. The aims of this study are to improve adherence and control of late clinical issues, which are predominant factors for racial disparities in kidney recipients, through a technology-enabled, telehealth-delivered, 4-level intervention. METHODS The Multifaceted Intervention to Improve Graft Outcome Disparities in African American Kidney Transplants (MITIGAAT) study is a 24-month, 2-arm, single-center (Medical University of South Carolina), 1:1 randomized controlled trial involving 190 participants (95 in each arm), measuring the impact on adherence and control of late clinical issues for racial disparities in kidney recipients, through a technology-enabled, telehealth-delivered, 4-level intervention. The key clinical issues for this study include tacrolimus variability, blood pressure, and glucose control (in those with diabetes mellitus). We will also assess the impact of the intervention on health care use (hospitalizations and emergency department visits) and conduct a cost-benefit analysis. Finally, we will assess the impact of the intervention on acute rejection and graft survival rates as compared with a large contemporary national cohort. RESULTS This study was funded in July 2023. Enrolled began in April 2024 and is expected to be complete in 2026. All patients will complete the study by the end of 2028. CONCLUSIONS In this protocol, we describe the study design, methods, aims, and outcome measures that will be used in the ongoing MITIGAAT clinical trials. TRIAL REGISTRATION ClinicalTrials.gov NCT06023615; https://www.clinicaltrials.gov/study/NCT06023615. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/57784.
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Affiliation(s)
| | - Hannah Culpepper
- Medical University of South Carolina, Charleston, SC, United States
| | - Deanna DeHoff
- Medical University of South Carolina, Charleston, SC, United States
| | | | | | - Zemin Su
- Medical University of South Carolina, Charleston, SC, United States
| | - Jessica Chandler
- Medical University of South Carolina, Charleston, SC, United States
| | - Felicia Bartlett
- Medical University of South Carolina, Charleston, SC, United States
| | - Paige Dunton
- Medical University of South Carolina, Charleston, SC, United States
| | - Taylor Carcella
- Medical University of South Carolina, Charleston, SC, United States
| | - David Taber
- Medical University of South Carolina, Charleston, SC, United States
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Engen RM, Lemoine CP. Evaluation and post-transplant management of children after multi-organ-with-kidney transplantation. Pediatr Nephrol 2024; 39:2875-2885. [PMID: 38483593 DOI: 10.1007/s00467-024-06336-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 08/28/2024]
Abstract
Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research.
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Affiliation(s)
- Rachel M Engen
- Department of Pediatrics, University of Wisconsin Madison, Madison, WI, USA.
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36
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Jadlowiec CC, Thongprayoon C, Suppadungsuk S, Tangpanithandee S, Leeaphorn N, Heilman R, Cooper M, Cheungpasitporn W. Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning. Clin Transplant 2024; 38:e15470. [PMID: 39367771 DOI: 10.1111/ctr.15470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 08/27/2024] [Accepted: 09/05/2024] [Indexed: 10/07/2024]
Abstract
BACKGROUND Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. METHODS Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12 356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5 mg/dL. Significant cluster characteristics were determined, and outcomes were compared. RESULTS The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12 356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). CONCLUSIONS In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.
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Affiliation(s)
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathobodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Supawit Tangpanithandee
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Napat Leeaphorn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Raymond Heilman
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Phoenix, Arizona, USA
| | - Matthew Cooper
- Division of Transplant Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Asfour NW, Zhang KC, Lu J, Reese PP, Saunders M, Peek M, White M, Persad G, Parker WF. Association of Race and Ethnicity With High Longevity Deceased Donor Kidney Transplantation Under the US Kidney Allocation System. Am J Kidney Dis 2024; 84:416-426. [PMID: 38636649 PMCID: PMC11421570 DOI: 10.1053/j.ajkd.2024.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/02/2024] [Accepted: 02/08/2024] [Indexed: 04/20/2024]
Abstract
RATIONALE & OBJECTIVE The US Kidney Allocation System (KAS) prioritizes candidates with a≤20% estimated posttransplant survival (EPTS) to receive high-longevity kidneys defined by a≤20% Kidney Donor Profile Index (KDPI). Use of EPTS in the KAS deprioritizes candidates with older age, diabetes, and longer dialysis durations. We assessed whether this use also disadvantages race and ethnicity minority candidates, who are younger but more likely to have diabetes and longer durations of kidney failure requiring dialysis. STUDY DESIGN Observational cohort study. SETTING & PARTICIPANTS Adult candidates for and recipients of kidney transplantation represented in the Scientific Registry of Transplant Recipients from January 2015 through December 2020. EXPOSURE Race and ethnicity. OUTCOME Age-adjusted assignment to≤20% EPTS, transplantation of a≤20% KDPI kidney, and posttransplant survival in longevity-matched recipients by race and ethnicity. ANALYTIC APPROACH Multivariable logistic regression, Fine-Gray competing risks survival analysis, and Kaplan-Meier and Cox proportional hazards methods. RESULTS The cohort included 199,444 candidates (7% Asian, 29% Black, 19% Hispanic or Latino, and 43% White) listed for deceased donor kidney transplantation. Non-White candidates had significantly higher rates of diabetes, longer dialysis duration, and were younger than White candidates. Adjusted for age, Asian, Black, and Hispanic or Latino candidates had significantly lower odds of having a ETPS score of≤20% (odds ratio, 0.86 [95% CI, 0.81-0.91], 0.52 [95% CI, 0.50-0.54], and 0.49 [95% CI, 0.47-0.51]), and were less likely to receive a≤20% KDPI kidney (sub-hazard ratio, 0.70 [0.66-0.75], 0.89 [0.87-0.92], and 0.73 [0.71-0.76]) compared with White candidates. Among recipients with≤20% EPTS scores transplanted with a≤20% KDPI deceased donor kidney, Asian and Hispanic recipients had lower posttransplant mortality (HR, 0.45 [0.27-0.77] and 0.63 [0.47-0.86], respectively) and Black recipients had higher but not statistically significant posttransplant mortality (HR, 1.22 [0.99-1.52]) compared with White recipients. LIMITATIONS Provider reported race and ethnicity data and 5-year post transplant follow-up period. CONCLUSIONS The US kidney allocation system is less likely to identify race and ethnicity minority candidates as having a≤20% EPTS score, which triggers allocation of high-longevity deceased donor kidneys. These findings should inform the Organ Procurement and Transplant Network about how to remedy the race and ethnicity disparities introduced through KAS's current approach of allocating allografts with longer predicted longevity to recipients with longer estimated posttransplant survival. PLAIN-LANGUAGE SUMMARY The US Kidney Allocation System prioritizes giving high-longevity, high-quality kidneys to patients on the waiting list who have a high estimated posttransplant survival (EPTS) score. EPTS is calculated based on the patient's age, whether the patient has diabetes, whether the patient has a history of organ transplantation, and the number of years spent on dialysis. Our analyses show that Asian, Black or African American, and Hispanic or Latino patients were less likely to receive high-longevity kidneys compared with White patients, despite having similar or better posttransplant survival outcomes.
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Affiliation(s)
- Nour W Asfour
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Kevin C Zhang
- Department of Medicine, University of Chicago, Chicago, Illinois
| | - Jessica Lu
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Peter P Reese
- Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Milda Saunders
- Department of Medicine, University of Chicago, Chicago, Illinois
| | - Monica Peek
- Department of Medicine, University of Chicago, Chicago, Illinois
| | - Molly White
- Department of Medicine, University of Chicago, Chicago, Illinois
| | - Govind Persad
- Sturm College of Law, University of Denver, Denver, Colorado
| | - William F Parker
- Department of Medicine, University of Chicago, Chicago, Illinois; MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, Illinois; Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
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Kwon H, Sandhu Z, Sarwar Z, Andacoglu OM. Impact of Medicaid expansion on kidney transplantation in the State Oklahoma. World J Transplant 2024; 14:92981. [PMID: 39295974 PMCID: PMC11317850 DOI: 10.5500/wjt.v14.i3.92981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/04/2024] [Accepted: 05/23/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND There is no data evaluating the impact of Medicaid expansion on kidney transplants (KT) in Oklahoma. AIM To investigate the impact of Medicaid expansion on KT patients in Oklahoma. METHODS The UNOS database was utilized to evaluate data pertaining to adult KT recipients in Oklahoma in the pre-and post-Medicaid eras. Bivariate analysis, Kaplan Meier analysis was used to estimate, and cox proportional models were utilized. RESULTS There were 2758 pre- and 141 recipients in the post-Medicaid expansion era. Post-expansion patients were more often non-United States citizens (2.3% vs 5.7%), American Indian, Alaskan, or Pacific Islander (7.8% vs 9.2%), Hispanic (7.4% vs 12.8%), or Asian (2.5% vs 8.5%) (P < 0.0001). Waitlist time was shorter in the post-expansion era (410 vs 253 d) (P = 0.0011). Living donor rates, pre-emptive transplants, re-do transplants, delayed graft function rates, kidney donor profile index values, panel reactive antibodies levels, and insurance types were similar. Patients with public insurance were more frail. Despite increased early (< 6 months) rejection rates, 1-year patient and graft survival were similar. In Cox proportional hazards model, male sex, American Indian, Alaskan or Pacific Islander race, public insurance, and frailty category were independent risk factors for death at 1 year. Medicaid expansion was not associated with graft failure or patient survival (adjusted hazard ratio: 1.07; 95%CI: 0.26-4.41). CONCLUSION Medicaid expansion in Oklahoma is associated with increased KT access for non-White/non-Black and non-United States citizen patients with shorter wait times. 1-year graft and patient survival rates were similar before and after expansion. Medicaid expansion itself was not independently associated with graft or patient survival outcomes. Ongoing research is necessary to determine the long-term effects of Medicaid expansion.
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Affiliation(s)
- Hyoshin Kwon
- Department of Surgery, Division of Transplantation, Ou College of Medicine, OK 73104, United States
| | - Zoya Sandhu
- Department of Internal Medicine, University of Oklahoma, Tulsa School of Community Medicine, Tulsa, OK 74135, United States
| | - Zoona Sarwar
- Department of Surgery, University of Oklahoma College of Medicine, Oklahoma, OK 73104, United States
| | - Oya M Andacoglu
- Department of Surgery, University of Oklahoma College of Medicine, Oklahoma, OK 73104, United States
- Department of Transplantation and Advanced Hepatobiliary Surgery, University of Utah, Salt Lake, UT 84112, United States
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Gonzalez FM, Gonzalez Cohens FDR. Kidney transplantation outcomes: Is it possible to improve when good results are falling down? World J Transplant 2024; 14:91214. [PMID: 39295975 PMCID: PMC11317855 DOI: 10.5500/wjt.v14.i3.91214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 04/30/2024] [Accepted: 05/28/2024] [Indexed: 07/31/2024] Open
Abstract
Famure et al describe that close to 50% of their patients needed early or very early hospital readmissions after their kidney transplantation. As they taught us the variables related to those outcomes, we describe eight teaching capsules that may go beyond what they describe in their article. First two capsules talk about the ideal donors and recipients we should choose for avoiding the risk of an early readmission. The third and fourth capsules tell us about the reality of cadaveric donors and recipients with comorbidities, and the way transplant physicians should choose them to maximize survival. Fifth capsule shows that any mistake can result in an early readmission, and thus, in poorer outcomes. Sixth capsule talks about economic losses of early readmissions, cost-effectiveness of transplantation, and how to improve outcomes and reduce costs by managing a risky patient-portfolio. Seventh capsule argues about knowing your risk behavior to better manage your portfolio; and Eighth capsule about the importance of the center experience in transplanting complex patients. We finish with some lessons of the importance of the transplantation process and the collaboration with other disciplines in order to prevent the conditions that lead to early readmissions.
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Affiliation(s)
- Fernando M Gonzalez
- Department of Nephrology, Faculty of Medicine, Universidad de Chile, Santiago 7500922, Chile
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Haq K, Yadav A, Mejia C. Approach to Kidney Allograft Dysfunction: A Brief Review. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:416-426. [PMID: 39232612 DOI: 10.1053/j.akdh.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/06/2024] [Accepted: 06/12/2024] [Indexed: 09/06/2024]
Abstract
It is important for providers caring for kidney transplant recipients to be familiar with the common causes of allograft dysfunction. Early detection of allograft dysfunction leads to timely management, with the goal of preventing or delaying progression to allograft failure. Although transplant rejection is always a concern, the differential diagnoses for allograft dysfunction are broad and include perioperative complications, infections, recurrent disease, and calcineurin nephrotoxicity. In this review, we will go over early and late causes of allograft dysfunction and discuss the basic workup and principles of management for each condition.
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Affiliation(s)
- Kanza Haq
- Division of Nephrology, Johns Hopkins University, Baltimore, MD
| | - Anju Yadav
- Division of Nephrology and Hypertension, Thomas Jefferson University, Philadelphia, PA
| | - Christina Mejia
- Division of Nephrology, Johns Hopkins University, Baltimore, MD.
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41
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Abu Jawdeh BG, Me HM. Immunosuppression in Kidney Transplant Recipients: An Update for the General Nephrologist. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:408-415. [PMID: 39232611 DOI: 10.1053/j.akdh.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 04/29/2024] [Accepted: 05/02/2024] [Indexed: 09/06/2024]
Abstract
Over the last 7 decades, kidney transplantation has evolved from an experiment between identical twins to becoming the gold standard treatment for end-stage kidney disease. To date, mycophenolate and calcineurin inhibitors, with or without prednisone, continue to constitute the backbone of modern maintenance immunosuppression. Despite major strides in improving acute rejection, long-term outcomes remain suboptimal with current regimens. Alternatives to calcineurin inhibitors such as belatacept and mammalian targets of rapamycin inhibitors exist; however, their wider-scale adoption remains relatively delayed due to concerns about increased rejection rates. In addition to continuing the investigation of steroid and calcineurin inhibitor sparing protocols, it is time to identify measurable surrogates for meaningful long-term graft survival. iBOX, a dynamic risk-prediction tool that predicts long-term death-censored graft failure could be a potential surrogate end point for future immunosuppression clinical trials. In this review, we summarize the landmark studies supporting current immunosuppression protocols and briefly discuss challenges and future directions.
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Affiliation(s)
| | - Hay Me Me
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, Phoenix, AZ
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Savoye E, Santin G, Legeai C, Kerbaul F, Gaillard F, Pastural M. Comparison of Kidney Graft Function and Survival in an Emulated Trial With Living Donors and Brain-Dead Donors. Transpl Int 2024; 37:13208. [PMID: 39267619 PMCID: PMC11391114 DOI: 10.3389/ti.2024.13208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/25/2024] [Indexed: 09/15/2024]
Abstract
Living donation (LD) transplantation is the preferred treatment for kidney failure as compared to donation after brain death (DBD), but age may play a role. We compared the 1-year estimated glomerular filtration rate (eGFR) after kidney transplantation for recipients of LD and DBD stratified by recipient and donor age between 2015 and 2018 in a matched cohort. The strength of the association between donation type and 1-year eGFR differed by recipient age (P interaction < 0.0001). For LD recipients aged 40-54 years versus same-aged DBD recipients, the adjusted odds ratio (aOR) for eGFR ≥60 mL/min/1.73 m2 was 1.48 (95% CI: 1.16-1.90). For DBD recipients aged ≥ 60 years, the aOR was 0.18 (95% CI: 0.12-0.29) versus DBD recipients aged 40-54 years but was 0.91 (95% CI: 0.67-1.24) versus LD recipients aged ≥60 years. In the matched cohort, 4-year graft and patient survival differed by donor age and type. As compared with DBD grafts, LD grafts increased the proportion of recipients with 1-year eGFR ≥60 mL/min/1.73 m2. Recipients aged ≥60 years benefited most from LD transplantation, even if the donor was aged ≥60 years. For younger recipients, large age differences between donor and recipient could also be addressed with a paired exchange program.
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Affiliation(s)
- Emilie Savoye
- Direction Prélèvement Greffe Organes-Tissus, Agence de la Biomédecine, Saint-Denis La Plaine, France
| | - Gaëlle Santin
- Direction Prélèvement Greffe Organes-Tissus, Agence de la Biomédecine, Saint-Denis La Plaine, France
| | - Camille Legeai
- Direction Prélèvement Greffe Organes-Tissus, Agence de la Biomédecine, Saint-Denis La Plaine, France
| | - François Kerbaul
- Direction Prélèvement Greffe Organes-Tissus, Agence de la Biomédecine, Saint-Denis La Plaine, France
| | - François Gaillard
- Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Myriam Pastural
- Direction Prélèvement Greffe Organes-Tissus, Agence de la Biomédecine, Saint-Denis La Plaine, France
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Mupfudze TG, Martinez A, Noreen SM, Stewart DE, Schold JD, Cartwright L. Individual-level social determinants of health and disparities in access to kidney transplant and waitlist mortality. PLoS One 2024; 19:e0308407. [PMID: 39167588 PMCID: PMC11338441 DOI: 10.1371/journal.pone.0308407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 07/23/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND Comprehensive, individual-level social determinants of health (SDOH) are not collected in national transplant registries, limiting research aimed at understanding the relationship between SDOH and waitlist outcomes among kidney transplant candidates. METHODS We merged Organ Procurement and Transplantation Network data with individual-level SDOH data from LexisNexis, a commercial data vendor, and conducted a competing risk analysis to determine the association between individual-level SDOH and the cumulative incidence of living donor kidney transplant (LDKT), deceased donor kidney transplant (DDKT), and waitlist mortality. We included adult kidney transplant candidates placed on the waiting list in 2020, followed through December 2023. RESULTS In multivariable analysis, having public insurance (Medicare or Medicaid), less than a college degree, and any type of derogatory record (liens, history of eviction, bankruptcy and/ felonies) were associated with lower likelihood of LDKT. Compared with patients with estimated individual annual incomes ≤ $30,000, patients with incomes ≥ $120,000 were more likely to receive a LDKT (sub distribution hazard ratio (sHR), 2.52; 95% confidence interval (CI), 2.03-3.12). Being on Medicare (sHR, 1.49; 95% CI, 1.42-1.57), having some college or technical school, or at most a high school diploma were associated with a higher likelihood of DDKT. Compared with patients with incomes ≤ $30,000, patients with incomes ≥ $120,000 were less likely to receive a DDKT (sHR, 0.60; 95% CI, 0.51-0.71). Lower individual annual income, having public insurance, at most a high school diploma, and a record of liens or eviction were associated with higher waitlist mortality. CONCLUSIONS Patients with adverse individual-level SDOH were less likely to receive LDKT, more likely to receive DDKT, and had higher risk of waitlist mortality. Differential relationships between SDOH, access to LDKT, DDKT, and waitlist mortality suggest the need for targeted interventions aimed at decreasing waitlist mortality and increasing access to LDKT among patients with adverse SDOH.
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Affiliation(s)
- Tatenda G. Mupfudze
- Research Department, United Network for Organ Sharing, Richmond, Virginia, United States of America
| | - Alina Martinez
- Research Department, United Network for Organ Sharing, Richmond, Virginia, United States of America
| | - Samantha M. Noreen
- Research Department, United Network for Organ Sharing, Richmond, Virginia, United States of America
| | - Darren E. Stewart
- Departments of Surgery, NYU Langone Health, New York, New York, United States of America
| | - Jesse D. Schold
- Departments of Surgery and Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America
| | - Laura Cartwright
- Research Department, United Network for Organ Sharing, Richmond, Virginia, United States of America
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Marks CR, Durand CM, Bowring MG, Hand J, Abidi MZ, Malinis M, Barnaba B, Patel H, Pavlakis M, Alonso CD. Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency. Transpl Infect Dis 2024; 26:e14287. [PMID: 38698669 DOI: 10.1111/tid.14287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 03/19/2024] [Accepted: 04/04/2024] [Indexed: 05/05/2024]
Abstract
PURPOSE Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. METHODS We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. RESULTS Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. CONCLUSIONS In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.
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Affiliation(s)
- Christin Rogers Marks
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | | | - Jonathan Hand
- Ochsner Health, New Orleans, Louisiana, USA
- Ochsner Clinical School, University of Queensland School of Medicine, New Orleans, Louisiana, USA
| | - Maheen Z Abidi
- Division of Infectious Disease, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | | | | | - Het Patel
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Martha Pavlakis
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Carolyn D Alonso
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Fujieda K, Tanaka A, Kikuchi R, Takai N, Saito S, Yasuda Y, Sano Y, Kato M, Furuhashi K, Maruyama S. Changes in antibody titer after four and five doses of the SARS-CoV-2 vaccine in Japanese post-kidney transplant patients. Ther Apher Dial 2024; 28:489-498. [PMID: 38385762 DOI: 10.1111/1744-9987.14114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 01/19/2024] [Accepted: 02/06/2024] [Indexed: 02/23/2024]
Abstract
INTRODUCTION Immunosuppressed patients exhibit low antibody acquisition rates following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Kidney transplant recipients previously exhibited low antibody acquisition rates after two vaccine doses, which increased after the third dose. We evaluated antibody titers of Japanese post-kidney transplant patients after the fourth and fifth vaccinations. METHODS Antibody titers for SARS-CoV-2 spike protein were measured between 3 weeks and 3 months after the fourth or fifth vaccination. RESULTS Increased antibody acquisition rates were observed after the fourth (75.0% antibody-positive) and fifth (81.5% antibody-positive) vaccinations. The antibody-acquired group after the fourth vaccination exhibited a higher body mass index and estimated glomerular filtration rate (eGFR) than the non-acquired group. A higher eGFR was associated with antibody acquisition after the fifth vaccination. CONCLUSION In Japanese post-kidney transplant patients, the antibody acquisition rate increased with each vaccine additional dose. Additional vaccinations are recommended to protect against SARS-CoV-2 infection.
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Affiliation(s)
- Kumiko Fujieda
- Department of Nephrology, Nagoya University Hospital, Nagoya, Japan
| | - Akihito Tanaka
- Department of Nephrology, Nagoya University Hospital, Nagoya, Japan
| | - Ryosuke Kikuchi
- Department of Medical Technique, Nagoya University Hospital, Nagoya, Japan
- Division of Clinical Laboratory, Gifu University Hospital, Gifu, Japan
| | - Nami Takai
- Department of Nursing, Nagoya University Hospital, Nagoya, Japan
| | - Shoji Saito
- Department of Nephrology, Nagoya University Hospital, Nagoya, Japan
| | - Yoshinari Yasuda
- Department of Nephrology, Nagoya University Hospital, Nagoya, Japan
| | - Yuta Sano
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masashi Kato
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Alvarez A, Montgomery A, Galván NTN, Brewer ED, Rana A. Predicting wait time for pediatric kidney transplant: a novel index. Pediatr Nephrol 2024; 39:2483-2493. [PMID: 38216782 PMCID: PMC11199301 DOI: 10.1007/s00467-023-06232-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/06/2023] [Accepted: 11/07/2023] [Indexed: 01/14/2024]
Abstract
BACKGROUND Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors. METHODS A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS database was performed. The data was randomly divided into a training set, comprising two-thirds of the data, and a testing set, comprising one-third of the data. From the training set, univariable and multivariable logistic regressions were used to identify significant predictive factors affecting wait times. A predictive index was created using variables significant in the multivariable analysis. The index's ability to predict likelihood of transplantation within 1 year of listing was validated using ROC analysis on the training set. Validation of the index using ROC analysis was repeated on the testing set. RESULTS A total of 10 variables were found to be significant. The five most significant variables include the following: blood group, B (OR 0.65); dialysis status (OR 3.67); kidney disease etiology, SLE (OR 0.38); and OPTN region, 5 (OR 0.54) and 6 (OR 0.46). ROC analysis of the index on the training set yielded a c-statistic of 0.71. ROC analysis of the index on the testing set yielded a c-statistic of 0.68. CONCLUSIONS This index is a modest prognostic model to assess time to pediatric kidney transplantation. It is intended as a supplementary tool to guide patient management by providing clinicians with an individualized prospective timeline for each candidate. Early identification of candidates with potential for prolonged waiting times may help encourage more living donation including paired donation chains.
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Affiliation(s)
- Alexandra Alvarez
- Office of Student Affairs, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
| | - Ashley Montgomery
- Office of Student Affairs, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Nhu Thao Nguyen Galván
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Eileen D Brewer
- Division of Pediatric Nephrology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Abbas Rana
- Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
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Schilsky J, Dvorai RH, Yang C, Suo L, Saracino G, Shahbazov R. Belatacept based immunosuppression: What and when to combine? Transpl Immunol 2024; 85:102050. [PMID: 38810889 DOI: 10.1016/j.trim.2024.102050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION This study examines the effect of belatacept based salvage regimens on kidney transplant outcomes. METHODS This single-center retrospective study included all adult kidney transplant recipients between 2011 and 2022 who were converted to belatacept salvage therapy during their follow up. eGFR, graft survival, incidence of infections and neoplasia, histology and DSA data were collected through systematic review of the medical record. RESULTS Patients were divided into 3 groups based on salvage regimen: Mycophenolate mofetil/belatacept (MMF/Bela) (n = 28), low-dose Calcineurin inhibitors/belatacept (CNI/Bela) (n = 22), and low-dose Calcineurin inhibitors/ Mycophenolate mofetil /belatacept (CNI/MMF/Bela) (n = 13). Patients with antibody-mediated rejection were more likely to receive CNIs in addition to belatacept (low-dose CNI/MMF/Bela 54%, low-dose CNI/Bela 45%, MMF/Bela 3.6%, p < 0.001). DSA decreased in all groups after transition to belatacept by 15.67% (p = 0.15). No difference in Glomerular filtration rate (eGFR) over time was observed between the groups, and eGFR remained stable over the first year after transition to belatacept. The incidence of death and allograft failure was similar between the groups (low- dose CNI/MMF/Bela n = 3, low-dose CNI/Bela n = 7, MMF/Bela n = 4; p = 0.41). Patients in the low-dose CNI/Bela cohort who were transitioned to belatacept within 6 months from transplant showed a decline in eGFR over the first year after transition, while the other treatment cohorts demonstrated stable or slight increase in eGFR. CONCLUSIONS The present study demonstrates comparable transplant outcomes in terms of eGFR, graft survival, incidence of infections and neoplasia, rejection rate and donor specific antibody (DSA) in three belatacept-based maintenance immunosuppression regimens supporting the safety and efficacy of these therapeutic options.
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Affiliation(s)
- Juliana Schilsky
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Reut Hod Dvorai
- Department of Pathology and Laboratory Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Christine Yang
- Department of Pharmacy, Division of Transplantation, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Liye Suo
- Department of Pathology and Laboratory Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Giovanna Saracino
- Baylor Simmons Transplant Institute, Baylor University Medical Centre, Dallas, TX, USA
| | - Rauf Shahbazov
- Department of Surgery, Division of Transplantation, SUNY Upstate Medical University, Syracuse, NY, USA; Department of Surgery, Division of Transplantation, Albany Medical Center, Albany, USA.
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Orandi BJ, Li Y, Seckin T, Bae S, Lonze BE, Ren-Fielding CJ, Lofton H, Gujral A, Segev DL, McAdams-DeMarco M. Obesogenic Medication Use in End-Stage Kidney Disease and Association With Transplant Listing. Clin Transplant 2024; 38:e15414. [PMID: 39166467 PMCID: PMC11552690 DOI: 10.1111/ctr.15414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/02/2024] [Accepted: 07/03/2024] [Indexed: 08/23/2024]
Abstract
OBJECTIVES Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.
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Affiliation(s)
- Babak J. Orandi
- New York University Department of Surgery; New York, NY, USA
- New York University Department of Medicine; New York, NY, USA
| | - Yiting Li
- New York University Department of Surgery; New York, NY, USA
| | - Timur Seckin
- New York University Department of Surgery; New York, NY, USA
| | - Sunjae Bae
- New York University Department of Surgery; New York, NY, USA
| | - Bonnie E. Lonze
- New York University Department of Surgery; New York, NY, USA
| | | | - Holly Lofton
- New York University Department of Medicine; New York, NY, USA
| | - Akash Gujral
- New York University Department of Surgery; New York, NY, USA
| | - Dorry L. Segev
- New York University Department of Surgery; New York, NY, USA
- New York University Department of Population Health; New York, NY, USA
| | - Mara McAdams-DeMarco
- New York University Department of Surgery; New York, NY, USA
- New York University Department of Population Health; New York, NY, USA
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Zhou D, Leung J, Xiong Y, Ye S, Zhou W, Ye Q, Wang Y. Kidney transplantation from a systemic lupus erythematosus donor and 1-year follow-up: A case report. Transpl Immunol 2024; 85:102077. [PMID: 38950754 DOI: 10.1016/j.trim.2024.102077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 06/28/2024] [Indexed: 07/03/2024]
Abstract
Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in the immune environment after kidney transplantation (KT) are unclear, and the recovery of renal function is poorly understood. We present a case of KT from a deceased donor with SLE who was followed-up for one year. Although SLE-related hemangioma developed during the perioperative period, it was cured after interventional treatment. A pre-planned biopsy was performed one year after KT, and it was found that most of the pathological changes and immunofluorescent markers of lupus had resolved. Renal function was stable, and urinary protein and occult blood levels reduced one year after KT.
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Affiliation(s)
- Dawei Zhou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China
| | - Junto Leung
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China
| | - Yan Xiong
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China
| | - Shaojun Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China
| | - Wei Zhou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China; The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, Hunan, Province 410013, PR China.
| | - Yanfeng Wang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation， Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, Hubei Province 43007, PR China.
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Obayemi JE, Callans L, Nair N, Gao H, Gandla D, Loza BL, Gao S, Mohebnasab M, Trofe-Clark J, Jacobson P, Keating B. Assessing the Utility of a Genotype-Guided Tacrolimus Equation in African American Kidney Transplant Recipients: A Single Institution Retrospective Study. J Clin Pharmacol 2024; 64:944-952. [PMID: 38766706 DOI: 10.1002/jcph.2461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 02/26/2024] [Indexed: 05/22/2024]
Abstract
Tacrolimus metabolism is heavily influenced by the CYP3A5 genotype, which varies widely among African Americans (AA). We aimed to assess the performance of a published genotype-informed tacrolimus dosing model in an independent set of adult AA kidney transplant (KTx) recipients. CYP3A5 genotypes were obtained for all AA KTx recipients (n = 232) from 2010 to 2019 who met inclusion criteria at a single transplant center in Philadelphia, Pennsylvania, USA. Medical record data were used to calculate predicted tacrolimus clearance using the published AA KTx dosing equation and two modified iterations. Observed and model-predicted trough levels were compared at 3 days, 3 months, and 6 months post-transplant. The mean prediction error at day 3 post-transplant was 3.05 ng/mL, indicating that the model tended to overpredict the tacrolimus trough. This bias improved over time to 1.36 and 0.78 ng/mL at 3 and 6 months post-transplant, respectively. Mean absolute prediction error-a marker of model precision-improved with time to 2.33 ng/mL at 6 months. Limiting genotype data in the model decreased bias and improved precision. The bias and precision of the published model improved over time and were comparable to studies in previous cohorts. The overprediction observed by the published model may represent overfitting to the initial cohort, possibly limiting generalizability.
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Affiliation(s)
- Joy E Obayemi
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Lauren Callans
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Nikhil Nair
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Hui Gao
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Divya Gandla
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Bao-Li Loza
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Sarah Gao
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Maedeh Mohebnasab
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Jennifer Trofe-Clark
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Pamala Jacobson
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Brendan Keating
- Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
- Department of Surgery, New York University, New York, NY, USA
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