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1
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Aubert O, Ursule-Dufait C, Brousse R, Gueguen J, Racapé M, Raynaud M, Van Loon E, Pagliazzi A, Huang E, Jordan SC, Chavin KD, Gupta G, Kumar D, Alhamad T, Anand S, Sanchez-Garcia J, Abdalla BA, Hogan J, Garro R, Dadhania DM, Jain P, Mandelbrot DA, Naesens M, Dandamudi R, Dharnidharka VR, Anglicheau D, Lefaucheur C, Loupy A. Cell-free DNA for the detection of kidney allograft rejection. Nat Med 2024; 30:2320-2327. [PMID: 38824959 PMCID: PMC11333280 DOI: 10.1038/s41591-024-03087-3] [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: 11/02/2023] [Accepted: 05/24/2024] [Indexed: 06/04/2024]
Abstract
Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .
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Affiliation(s)
- Olivier Aubert
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Department of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Cindy Ursule-Dufait
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
| | - Romain Brousse
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
| | - Juliette Gueguen
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
| | - Maud Racapé
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
| | - Marc Raynaud
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
| | - Elisabet Van Loon
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Angelica Pagliazzi
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Edmund Huang
- Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Stanley C Jordan
- Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Kenneth D Chavin
- Division of Abdominal Organ Transplant, Department of Surgery, Temple University Hospital, Philadelphia, PA, USA
| | - Gaurav Gupta
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
| | - Dhiren Kumar
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
| | - Tarek Alhamad
- Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Sanjiv Anand
- Intermountain Medical Center, Transplant Services, Murray, UT, USA
| | | | - Basmah A Abdalla
- Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Julien Hogan
- Department of Pediatric Nephrology, Robert Debré Hospital, Paris Cité University, Paris, France
| | - Rouba Garro
- Pediatric Nephrology Department, Children Healthcare of Atlanta, Emory University, Atlanta, GA, USA
| | | | - Pranjal Jain
- Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
| | - Didier A Mandelbrot
- Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Maarten Naesens
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Raja Dandamudi
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Vikas R Dharnidharka
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Dany Anglicheau
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Department of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Carmen Lefaucheur
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Alexandre Loupy
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France.
- Department of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
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2
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Berger M, Baliker M, Van Gelder T, Böhmig GA, Mannon RB, Kumar D, Chadban S, Nickerson P, Lee LA, Djamali A. Chronic Active Antibody-mediated Rejection: Opportunity to Determine the Role of Interleukin-6 Blockade. Transplantation 2024; 108:1109-1114. [PMID: 37941113 PMCID: PMC11042519 DOI: 10.1097/tp.0000000000004822] [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: 06/07/2023] [Revised: 07/17/2023] [Accepted: 08/16/2023] [Indexed: 11/10/2023]
Abstract
Chronic active antibody-mediated rejection (caAMR) is arguably the most important cause of late kidney allograft failure. However, there are no US Food and Drug Administration (FDA)-approved treatments for acute or chronic AMR and there is no consensus on effective treatment. Many trials in transplantation have failed because of slow and/or inadequate enrollment, and no new agent has been approved by the FDA for transplantation in over a decade. Several lines of evidence suggest that interleukin-6 is an important driver of AMR, and clazakizumab, a humanized monoclonal antibody that neutralizes interleukin-6, has shown promising results in phase 2 studies. The IMAGINE trial (Interleukin-6 Blockade Modifying Antibody-mediated Graft Injury and Estimated Glomerular Filtration Rate Decline) (NCT03744910) is the first to be considered by the FDA using a reasonably likely surrogate endpoint (slope of estimated glomerular filtration rate decline >1 y) for accelerated approval and is the only ongoing clinical trial for the treatment of chronic rejection. This trial offers us the opportunity to advance the care for our patients in need, and this article is a call to action for all transplant providers caring for patients with caAMR.
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Affiliation(s)
- Mel Berger
- Departments of Pediatrics and Pathology, Case Western Reserve University, Cleveland, OH
| | | | - Teun Van Gelder
- Department Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Georg A. Böhmig
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Roslyn B. Mannon
- Division of Nephrology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
| | - Deepali Kumar
- Department of Medicine, Division of Transplant Infectious Disease, Ajmera Transplant Centre, Toronto, ON, Canada
| | - Steve Chadban
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Peter Nickerson
- Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Laurie A. Lee
- Research and Development, Transplant Therapeutic Area, CSL Behring, King of Prussia, Pennsylvania, PA
| | - Arjang Djamali
- Department of Medicine, Maine Medical Center, Portland, ME
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3
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Tran J, Alrajhi I, Chang D, Sherwood KR, Keown P, Gill J, Kadatz M, Gill J, Lan JH. Clinical relevance of HLA-DQ eplet mismatch and maintenance immunosuppression with risk of allosensitization after kidney transplant failure. Front Genet 2024; 15:1383220. [PMID: 38638120 PMCID: PMC11024336 DOI: 10.3389/fgene.2024.1383220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 03/21/2024] [Indexed: 04/20/2024] Open
Abstract
The optimal immunosuppression management in patients with a failed kidney transplant remains uncertain. This study analyzed the association of class II HLA eplet mismatches and maintenance immunosuppression with allosensitization after graft failure in a well characterized cohort of 21 patients who failed a first kidney transplant. A clinically meaningful increase in cPRA in this study was defined as the cPRA that resulted in 50% reduction in the compatible donor pool measured from the time of transplant failure until the time of repeat transplantation, death, or end of study. The median cPRA at the time of failure was 12.13% (interquartile ranges = 0.00%, 83.72%) which increased to 62.76% (IQR = 4.34%, 99.18%) during the median follow-up of 27 (IQR = 18, 39) months. High HLA-DQ eplet mismatches were significantly associated with an increased risk of developing a clinically meaningful increase in cPRA (p = 0.02) and de novo DQ donor-specific antibody against the failed allograft (p = 0.02). We did not observe these associations in patients with high HLA-DR eplet mismatches. Most of the patients (88%) with a clinically meaningful increase in cPRA had both a high DQ eplet mismatch and a reduction in their immunosuppression, suggesting the association is modified by immunosuppression. The findings suggest HLA-DQ eplet mismatch analysis may serve as a useful tool to guide future clinical studies and trials which assess the management of immunosuppression in transplant failure patients who are repeat transplant candidates.
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Affiliation(s)
- Jenny Tran
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Ibrahim Alrajhi
- King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Doris Chang
- Vancouver Coastal Health Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Karen R. Sherwood
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Paul Keown
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Vancouver Coastal Health Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Jagbir Gill
- Division of Nephrology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Providence Health Care Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Matthew Kadatz
- Vancouver Coastal Health Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Division of Nephrology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - John Gill
- Division of Nephrology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Providence Health Care Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - James H. Lan
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Vancouver Coastal Health Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Division of Nephrology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
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Bathini S, Jha V. Immunosuppressive Practices in Failed Kidney Grafts in South Asia-An Investigative Survey. Kidney Int Rep 2024; 9:1107-1110. [PMID: 38765570 PMCID: PMC11101818 DOI: 10.1016/j.ekir.2024.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 01/09/2024] [Accepted: 01/11/2024] [Indexed: 05/22/2024] Open
Affiliation(s)
| | - Vivekanand Jha
- George Institute for Global Health, UNSW, New Delhi, India
- Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India
- School of Public Health, Imperial College, London, UK
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Samarasinghe A, Wong G, Teixeira-Pinto A, Johnson DW, Hawley C, Pilmore H, Mulley WR, Roberts MA, Polkinghorne KR, Boudville N, Davies CE, Viecelli AK, Ooi E, Larkins NG, Lok C, Lim WH. Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss. Clin Kidney J 2024; 17:sfad245. [PMID: 38468698 PMCID: PMC10926326 DOI: 10.1093/ckj/sfad245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Indexed: 03/13/2024] Open
Abstract
Background Diabetes mellitus (DM) is associated with a greater risk of mortality in kidney transplant patients, primarily driven by a greater risk of cardiovascular disease (CVD)-related mortality. However, the associations between diabetes status at time of first allograft loss and mortality on dialysis remain unknown. Methods All patients with failed first kidney allografts transplanted in Australia and New Zealand between 2000 and 2020 were included. The associations between diabetes status at first allograft loss, all-cause and cause-specific mortality were examined using competing risk analyses, separating patients with diabetes into those with pre-transplant DM or post-transplant diabetes mellitus (PTDM). Results Of 3782 patients with a median (IQR) follow-up duration of 2.7 (1.1-5.4) years, 539 (14%) and 390 (10%) patients had pre-transplant DM or developed PTDM, respectively. In the follow-up period, 1336 (35%) patients died, with 424 (32%), 264 (20%) and 199 (15%) deaths attributed to CVD, dialysis withdrawal and infection, respectively. Compared to patients without DM, the adjusted subdistribution HRs (95% CI) for pre-transplant DM and PTDM for all-cause mortality on dialysis were 1.47 (1.17-1.84) and 1.47 (1.23-1.76), respectively; for CVD-related mortality were 0.81 (0.51-1.29) and 1.02 (0.70-1.47), respectively; for infection-related mortality were 1.84 (1.02-3.35) and 2.70 (1.73-4.20), respectively; and for dialysis withdrawal-related mortality were 1.71 (1.05-2.77) and 1.51 (1.02-2.22), respectively. Conclusions Patients with diabetes at the time of kidney allograft loss have a significant survival disadvantage, with the excess mortality risk attributed to infection and dialysis withdrawal.
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Affiliation(s)
- Amali Samarasinghe
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia
| | - Germaine Wong
- School of Public Health, Faculty of Medicine and Health, Sydney University, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
- Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, Australia
| | - Armando Teixeira-Pinto
- School of Public Health, Faculty of Medicine and Health, Sydney University, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - David W Johnson
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Queensland, Australia
- Australasian Kidney Trials Network, University of Queensland, Queensland, Australia
- Translational Research Institute, Queensland, Australia
| | - Carmel Hawley
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Queensland, Australia
- Australasian Kidney Trials Network, University of Queensland, Queensland, Australia
- Translational Research Institute, Queensland, Australia
| | - Helen Pilmore
- Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand
- Department of Medicine, Auckland University, Auckland, New Zealand
| | - William R Mulley
- Department of Nephrology, Monash Medical Centre, Melbourne, Australia
- Department of Medicine, Monash University, Melbourne, Australia
| | - Matthew A Roberts
- Eastern Health Clinical School, Monash University, Victoria, Australia
| | - Kevan R Polkinghorne
- Department of Nephrology and Medicine, Monash Medical Centre, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Neil Boudville
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia
- Internal Medicine, University of Western Australia Medical School, Perth, Australia
| | - Christopher E Davies
- Faculty of Health and Medical Science, Adelaide University Medical School, South Australia, Australia
- Australia and New Zealand Dialysis and Transplant Registry, South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Andrea K Viecelli
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Queensland, Australia
- Australasian Kidney Trials Network, University of Queensland, Queensland, Australia
| | - Esther Ooi
- School of Biomedical Sciences, University of Western Australia, Western Australia, Australia
| | - Nicholas G Larkins
- Department of Nephrology, Perth Children's Hospital, Perth, Western Australia, Australia
- School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia
| | - Charmaine Lok
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Division of Nephrology, Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada
| | - Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia
- Internal Medicine, University of Western Australia Medical School, Perth, Australia
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6
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Babiker A, Karadkhele G, Bombin A, Watkins R, Robichaux C, Smith G, Beechar VB, Steed DB, Jacob JT, Read TD, Satola S, Larsen CP, Kraft CS, Pouch SM, Woodworth MH. The Burden and Impact of Early Post-transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005-2021. Open Forum Infect Dis 2024; 11:ofae060. [PMID: 38464488 PMCID: PMC10924447 DOI: 10.1093/ofid/ofae060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 02/06/2024] [Indexed: 03/12/2024] Open
Abstract
Background Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score-weighted sensitivity, and subgroup analyses were performed. Results Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%-1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31-0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21-8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92-55.5; subdistribution aHR, 7.15; 95% CI, 0.95-53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.
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Affiliation(s)
- Ahmed Babiker
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Geeta Karadkhele
- Emory Transplant Center and Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Andrei Bombin
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Rockford Watkins
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Chad Robichaux
- Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Gillian Smith
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
- Georgia Emerging Infections Program, Atlanta, Georgia, USA
- Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, USA
| | - Vivek B Beechar
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Danielle B Steed
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Jesse T Jacob
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Timothy D Read
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Sarah Satola
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Christian P Larsen
- Emory Transplant Center and Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Colleen S Kraft
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Stephanie M Pouch
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Michael H Woodworth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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7
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Ostadi F, Anzali BC, Mehryar HR. Relationship between serum lactate dehydrogenase levels and prognosis in patients infected with omicron and delta variants of COVID-19: A cross-sectional study. Toxicol Rep 2023; 11:368-373. [PMID: 37868806 PMCID: PMC10589382 DOI: 10.1016/j.toxrep.2023.10.003] [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: 09/12/2023] [Revised: 10/08/2023] [Accepted: 10/09/2023] [Indexed: 10/24/2023] Open
Abstract
Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However, there is currently insufficient evidence regarding the role of lactate dehydrogenase (LDH) in COVID-19 and its prognostic implications. This retrospective cross-sectional study analyzed data from all patients hospitalized at Urmia Imam Khomeini Hospital between September 2021 and March 2023 with a diagnosis of COVID-19 involving the Delta and Omicron variants. Patient information, including age, sex, duration of hospitalization, admission to the intensive care unit (ICU), strain type, and outcomes, was extracted. Exclusion criteria encompassed myocardial infarction, lung, liver, blood, skeletal muscle diseases, injury, neoplasm, pancreatitis, pregnancy, poisoning, unwillingness to participate in the study, and the use of ascorbic acid. A total of 609 patients with an average age of 54.80 years were included in this study. Among these patients, 56.3% were female, and the mortality rate was 20.7%. The serum LDH levels were significantly higher in patients who succumbed to the disease (P < 0.001), those requiring ICU admission (P < 0.001), and female patients (P = 0.02) compared to other groups. Furthermore, the LDH serum levels exhibited a strong significant correlation with the duration of hospitalization (r = -0.11, P = 0.007). The results revealed that there is a difference in the mean serum LDH levels between deceased patients and discharged patients (P < 0.001). The findings indicate that elevated serum LDH levels are associated with increased mortality, prolonged hospitalization, ICU admission, and infection with the Delta variant of COVID-19.
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Affiliation(s)
- Fatemeh Ostadi
- Department of medicine, School of medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Babak Choobi Anzali
- Emergency Medicine, Department of emergency Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hamid Reza Mehryar
- Emergency Medicine, Department of emergency Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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8
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Corr M, Lawrie K, Baláž P, O'Neill S. Management of an aneurysmal arteriovenous fistula in kidney transplant recipients. Transplant Rev (Orlando) 2023; 37:100799. [PMID: 37804690 DOI: 10.1016/j.trre.2023.100799] [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: 08/03/2023] [Revised: 09/26/2023] [Accepted: 09/26/2023] [Indexed: 10/09/2023]
Abstract
Aneurysms remain the most common complication of an arteriovenous fistula created for dialysis access. The management of an aneurysmal arteriovenous fistula (AAVF) in kidney transplant recipients remains contentious with a lack of clear clinical guidelines. Recipients of a functioning graft do not require the fistula for dialysis access, however risk of graft failure and needing the access at a future date must be considered. In this review we outline the current evidence in the assessment and management of a transplant recipient with an AAVF. We will describe our recommended five-step approach to assessing an AAVF in transplant patients; 1.) Define AAVF 2.) Risk assess AAVF 3.) Assess transplant graft function and future graft failure risk 4.) Consider future renal replacement therapy options 5.) Vascular mapping to assess future vascular access options. Then we will describe the current therapeutic options and when they would most appropriately be employed.
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Affiliation(s)
- Michael Corr
- Centre of Public Health - Queen's University Belfast, Belfast, United Kingdom; Regional Nephrology & Transplant Unit-Belfast Health and Social Care Trust, Belfast, United Kingdom.
| | - Kateřina Lawrie
- Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Peter Baláž
- Division of Vascular Surgery, University Hospital Královské Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Cardiocenter, University Hospital Královské Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Vascular Surgery, National Institute for Cardiovascular Disease, Bratislava, Slovak Republic
| | - Stephen O'Neill
- Regional Nephrology & Transplant Unit-Belfast Health and Social Care Trust, Belfast, United Kingdom; Centre of Medical Education, Queen's University Belfast, Belfast, United Kingdom
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9
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Budhiraja P, Nguyen M, Heilman R, Kaplan B. The Role of Allograft Nephrectomy in the Failing Kidney Transplant. Transplantation 2023; 107:2486-2496. [PMID: 37122077 DOI: 10.1097/tp.0000000000004625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
Patients with failed renal allografts have associated increased morbidity and mortality. The individualization of immunosuppression taper is the key element in managing these patients to avoid graft intolerance and sensitization while balancing the risk of continued immunosuppression. Most patients with uncomplicated chronic allograft failure do not require allograft nephrectomy (AN), and there is no clear evidence that it improves outcomes. The AN procedure is associated with variable morbidity and mortality. It is reserved mainly for early technical graft failure or in symptomatic cases associated with allograft infection, malignancy, or graft intolerance syndrome. It may also be considered in those who cannot tolerate immunosuppression and are at high risk for graft intolerance. AN has been associated with an increased risk of sensitization due to inflammatory response from surgery, immunosuppression withdrawal with allograft failure, and retained endovascular tissue. Although it is presumed that for-cause AN after transplant failure is associated with sensitization, it remains unclear whether elective AN in patients who remain on immunotherapy may prevent sensitization. The current practice of immunosuppression taper has not been shown to prevent sensitization or increase infection risk, but current literature is limited by selection bias and the absence of medication adherence data. We discuss the management of failed allografts based on retransplant candidacy, wait times, risk of graft intolerance syndrome, and immunosuppression side effects. Many unanswered questions remain, and future prospective randomized trials are needed to help guide evidence-based management.
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Affiliation(s)
| | | | | | - Bruce Kaplan
- Department of Medicine, Colorado Center for Transplantation Care, Research and Education (CCTCARE), University of Colorado, Aurora, CO
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10
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Tanriover C, Copur S, Basile C, Ucku D, Kanbay M. Dialysis after kidney transplant failure: how to deal with this daunting task? J Nephrol 2023; 36:1777-1787. [PMID: 37676635 DOI: 10.1007/s40620-023-01758-x] [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: 12/06/2022] [Accepted: 08/06/2023] [Indexed: 09/08/2023]
Abstract
The best treatment for patients with end-stage kidney disease is kidney transplantation, which, if successful provides both a reduction in mortality and a better quality of life compared to dialysis. Although there has been significant improvement in short-term outcomes after kidney transplantation, long-term graft survival still remains insufficient. As a result, there has been an increase in the number of individuals who need dialysis again after kidney transplant failure, and increasingly contribute to kidney transplant waiting lists. Starting dialysis after graft failure is a difficult task not only for the patients, but also for the nephrologists and the care team. Furthermore, recommendations for management of dialysis after kidney graft loss are lacking. Aim of this narrative review is to provide a perspective on the role of dialysis in the management of patients with failed kidney allograft. Although numerous studies have reported higher mortality in patients undergoing dialysis following kidney allograft failure, reports are contrasting. A patient-centered, individualized approach should drive the choices of initiating dialysis, dialysis modality, maintenance of immunosuppressive drugs and vascular access.
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Affiliation(s)
- Cem Tanriover
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Carlo Basile
- Associazione Nefrologica Gabriella Sebastio, Via Battisti 192, 74121, Taranto, Italy.
| | - Duygu Ucku
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
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11
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Ogawa L, Beaird OE, Schaenman JM. Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications. FRONTIERS IN NEPHROLOGY 2023; 3:1149116. [PMID: 37675348 PMCID: PMC10479655 DOI: 10.3389/fneph.2023.1149116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 07/17/2023] [Indexed: 09/08/2023]
Abstract
Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced "IS" varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.
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Affiliation(s)
| | | | - Joanna M. Schaenman
- Division of Infectious Diseases, David Geffen School of Medicine at University of California—Los Angeles, Los Angeles, CA, United States
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12
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McDonald M. Allograft nephrectomy vs. no nephrectomy for failed renal transplants. FRONTIERS IN NEPHROLOGY 2023; 3:1169181. [PMID: 37675360 PMCID: PMC10479781 DOI: 10.3389/fneph.2023.1169181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 06/13/2023] [Indexed: 09/08/2023]
Abstract
The role of allograft nephrectomy (AN) in failed renal transplants is a topic of debate, owing to controversial results reported in the literature and the fact that most of the studies are limited by a retrospective design and small numbers of participants. Allograft nephrectomy is most likely of benefit in the patient with recurrent allograft intolerance syndrome (AIS) following pulse steroids. Immunosuppression weaning in the presence of clinical signs related to a chronic inflammatory state is also reasonable grounds to pursue AN. Studies are mainly inconclusive but suggest that AN has no overall benefit for allograft survival after retransplant. This topic is still of interest in the transplant field and is particularly relevant for patients who are likely to require retransplantation within their lifetime. Further assessment is needed in the form of randomized controlled trials that control for various AN indications and immunosuppression regimens, and have clearly defined survival outcomes.
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Affiliation(s)
- Michelle McDonald
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
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13
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Truchot A, Raynaud M, Loupy A. Excess mortality after kidney transplantation: does sex matter? Kidney Int 2023; 103:1023-1024. [PMID: 37210193 DOI: 10.1016/j.kint.2023.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 05/22/2023]
Abstract
Understanding sex differences in graft outcomes within the course of kidney transplantation is needed to unravel factors leading to the observed disparities and further improve patient management. In this issue, Vinson et al. presented a relative survival analysis comparing the excess risk of mortality in female and male recipients after kidney transplantation. This commentary discusses the major findings but also the challenges of the use of registry data to conduct large-scale analyses.
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Affiliation(s)
- Agathe Truchot
- Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, Institut National de la Santé et de la Recherche Médicale, U-970, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Marc Raynaud
- Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, Institut National de la Santé et de la Recherche Médicale, U-970, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Alexandre Loupy
- Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, Institut National de la Santé et de la Recherche Médicale, U-970, Assistance Publique-Hôpitaux de Paris, Paris, France.
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14
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Vinson AJ, Zhang X, Dahhou M, Süsal C, Döhler B, Melk A, Sapir-Pichhadze R, Cardinal H, Wong G, Francis A, Pilmore H, Foster BJ. A multinational cohort study uncovered sex differences in excess mortality after kidney transplant. Kidney Int 2023; 103:1131-1143. [PMID: 36805451 DOI: 10.1016/j.kint.2023.01.022] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 01/14/2023] [Accepted: 01/19/2023] [Indexed: 02/21/2023]
Abstract
Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02-1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females.
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Affiliation(s)
- Amanda J Vinson
- Department of Medicine, Nephrology Division, Dalhousie University, Halifax, Nova Scotia, Canada.
| | - Xun Zhang
- Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation, Montréal, Québec, Canada
| | - Mourad Dahhou
- Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation, Montréal, Québec, Canada
| | - Caner Süsal
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany; Transplant Immunology Research Center of Excellence, Koç University, Istanbul, Turkey
| | - Bernd Döhler
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany
| | - Anette Melk
- Children's Hospital, Hannover Medical School, Hannover, Germany
| | - Ruth Sapir-Pichhadze
- Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation, Montréal, Québec, Canada; Department of Medicine, Division of Nephrology, McGill University, Montréal, Québec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada
| | - Heloise Cardinal
- Department of Medicine, Division of Nephrology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | - Germaine Wong
- School of Public Health, University of Sydney, Sydney, New South Wales, Australia
| | - Anna Francis
- School of Clinical Medicine, University of Queensland, Brisbane, Queensland, Australia; Department of Nephrology, Queensland Children's Hospital, Brisbane, Queensland, Australia
| | - Helen Pilmore
- Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand
| | - Bethany J Foster
- Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation, Montréal, Québec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada; Department of Pediatrics, Division of Nephrology, McGill University Faculty of Medicine, Montréal, Québec, Canada.
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15
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Au EHK, Chapman JR, Teixeira-Pinto A, Craig JC, Wong G. Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis. Transplantation 2023; 107:1359-1364. [PMID: 36683232 DOI: 10.1097/tp.0000000000004493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Cancer incidence and mortality may change with varying kidney allograft function and after graft loss. We aimed to quantify cancer incidence and mortality during periods with a functioning graft and after graft loss. METHODS We included all adult Australians aged 20 and above who commenced kidney replacement therapy between 1982 and 2014 using data from Australia and New Zealand Dialysis and Transplant Registry. We calculated the standardized incidence ratios and standardized mortality ratios (standardized against the Australian general population) for dialysis patients and transplant recipients during periods with a functioning graft and after graft loss. RESULTS A total of 44 765 dialysis patients without transplants, 13 443 with first kidney transplants, 2951 after first graft loss, 1010 with second transplants, and 279 after second graft loss were followed for 274 660 patient-years. Cancer incidence and mortality (per 100 000 patient-years) were 1564 and 760 in dialysis patients, 1564 and 689 in recipients of first transplants, 1188 and 390 after first graft loss, 1525 and 693 after second transplants, and 1645 and 779 after second graft loss. Cancer standardized incidence ratios and standardized mortality ratios (95% confidence intervals) were 1.15 (1.11-1.20) and 1.29 (1.21-1.36) for dialysis patients, 2.03 (1.94-2.13) and 2.50 (2.33-2.69) for recipients following their first transplant, 1.55 (1.29-1.85) and 1.40 (1.00-1.90) after first graft loss, 2.18 (1.79-2.63) and 3.00 (2.23-3.96) for second transplants, 2.59 (1.56-4.04) and 3.82 (1.75-7.25) after second graft loss. CONCLUSIONS In kidney transplant recipients, cancer incidence and mortality are highest during periods with a functioning graft and remained higher than in the general population even after graft loss.
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Affiliation(s)
- Eric H K Au
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
- School of Public Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
| | - Jeremy R Chapman
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - Armando Teixeira-Pinto
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
- School of Public Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
| | - Jonathan C Craig
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Germaine Wong
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
- School of Public Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
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16
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Murakami N, Reich AJ, Pavlakis M, Lakin JR. Conservative Kidney Management in Kidney Transplant Populations. Semin Nephrol 2023; 43:151401. [PMID: 37499572 PMCID: PMC10543459 DOI: 10.1016/j.semnephrol.2023.151401] [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] [Indexed: 07/29/2023]
Abstract
Conservative kidney management (CKM) has been increasingly accepted as a therapeutic option for seriously ill patients with advanced chronic kidney disease. CKM is active medical management of advanced chronic kidney disease without dialysis, with a focus on delaying the worsening of kidney disease and minimizing symptom burden. CKM may be considered a suitable option for kidney transplant recipients with poorly functioning and declining allografts, defined as patients with low estimated glomerular filtration rate (<20 mL/min per 1.73 m2) who are approaching allograft failure. CKM may be a fitting option for transplant patients facing high morbidity and mortality with or without dialysis resumption, and it should be offered as a choice for this patient population. In this review, we describe clinical considerations in caring for patients with poorly functioning and declining kidney allografts, especially the unique decision-making process around kidney replacement therapies. We discuss ways to incorporate CKM as an option for these patients. We also discuss financial and policy considerations in providing CKM for this population. Patients with poorly functioning and declining kidney allografts should be supported throughout transitions of care by an interprofessional and multidisciplinary team attuned to their unique challenges. Further research on when, who, and how to integrate CKM into existing care structures for patients with poorly functioning and declining kidney allografts is needed.
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Affiliation(s)
- Naoka Murakami
- Harvard Medical School, Boston, MA; Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA.
| | - Amanda J Reich
- Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA
| | - Martha Pavlakis
- Harvard Medical School, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA
| | - Joshua R Lakin
- Harvard Medical School, Boston, MA; Division of Palliative Medicine, Brigham and Women's Hospital, Boston, MA; Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, MA
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17
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Chen J, He ZX, Wang FK. RETRACTED ARTICLE: Evaluation of ferritin level in COVID-19 patients and its inflammatory response. APPLIED NANOSCIENCE 2023; 13:3121. [PMID: 35136706 PMCID: PMC8812356 DOI: 10.1007/s13204-021-02115-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 09/24/2021] [Indexed: 01/08/2023]
Affiliation(s)
- Jing Chen
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Zheng-Xin He
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Fun-Kun Wang
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
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18
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Bunthof K, Saboerali K, Wetering JVD, Nurmohamed A, Bemelman F, Zuilen AV, Brand JVD, Baas M, Hilbrands L. Can We Predict Graft Intolerance Syndrome After Kidney Transplant Failure? External Validation of a Previously Developed Model. Transpl Int 2023; 36:11147. [PMID: 37213489 PMCID: PMC10195885 DOI: 10.3389/ti.2023.11147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 04/25/2023] [Indexed: 05/23/2023]
Abstract
Previously we established a prediction model for graft intolerance syndrome requiring graft nephrectomy in patients with late kidney graft failure. The aim of this study is to determine generalizability of this model in an independent cohort. The validation cohort included patients with late kidney graft failure between 2008 and 2018. Primary outcome is the prognostic performance of our model, expressed as the area under the receiver operating characteristic curve (ROC-AUC), in the validation cohort. In 63 of 580 patients (10.9%) a graft nephrectomy was performed because of graft intolerance. The original model, which included donor age, graft survival and number of acute rejections, performed poorly in the validation cohort (ROC-AUC 0.61). After retraining of the model using recipient age at graft failure instead of donor age, the model had an average ROC-AUC of 0.70 in the original cohort and of 0.69 in the validation cohort. Our original model did not accurately predict the graft intolerance syndrome in a validation cohort. However, a retrained model including recipient age at graft failure instead of donor age performed moderately well in both the development and validation cohort enabling identification of patients with the highest and lowest risk of graft intolerance syndrome.
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Affiliation(s)
- Kim Bunthof
- Department of Nephrology, Radboud University Medical Centre, Nijmegen, Netherlands
- Department of Internal Medicine, Bravis Ziekenhuis, Roosendaal, Netherlands
| | - Khalid Saboerali
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | | | - Azam Nurmohamed
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Frederike Bemelman
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Arjan Van Zuilen
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
| | | | - Marije Baas
- Department of Nephrology, Radboud University Medical Centre, Nijmegen, Netherlands
| | - Luuk Hilbrands
- Department of Nephrology, Radboud University Medical Centre, Nijmegen, Netherlands
- *Correspondence: Luuk Hilbrands,
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19
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Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design. Trials 2022; 23:1042. [PMID: 36550562 PMCID: PMC9772593 DOI: 10.1186/s13063-022-06897-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 11/08/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. METHODS IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. DISCUSSION IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. TRIAL REGISTRATION ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.
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20
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Effect of Maintaining Immunosuppression After Kidney Allograft Failure on Mortality and Retransplantation. Transplant Direct 2022; 9:e1415. [DOI: 10.1097/txd.0000000000001415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 10/11/2022] [Indexed: 12/12/2022] Open
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21
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Cherukuri A, Rothstein DM. Regulatory and transitional B cells: potential biomarkers and therapeutic targets in organ transplantation. Curr Opin Organ Transplant 2022; 27:385-391. [PMID: 35950881 PMCID: PMC9474638 DOI: 10.1097/mot.0000000000001010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF THE REVIEW Regulatory B cells (Bregs) play a prominent role in various disease settings. While progress has been hindered by the lack of a specific Breg marker, new findings highlight their role modulating the alloimmune response and promoting allograft survival. RECENT FINDINGS Herein, we focus on the recent advances in Breg biology and their role in transplantation. We review studies showing that T-cell immunoglobulin and mucin domain 1 (TIM-1) is an inclusive and functional Breg marker in mice that may have human relevance. We highlight the utility of the B cell interleukin-10/tumor necrosis factor-alpha (IL-10/TNFα) ratio in identifying underlying immunological reactivity and predicting clinical outcomes in kidney transplantation. This may identify patients requiring more immunosuppression and provide insight into potential therapeutic approaches that can modulate the Breg: B effector cell (Beff) balance. SUMMARY Emerging data support Bregs as potent modulators of immune responses in humans. Their ability to promote allograft survival must await development of approaches to expand Bregs in vitro/in vivo . The low IL-10/TNFα ratio reflecting decreased Breg/Beff balance, predicts acute rejection (AR) and poorer outcomes in renal transplantation. It remains to be determined whether this paradigm can be extended to other allografts and whether therapy aiming to correct the relative deficiency of Bregs will improve outcomes.
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Affiliation(s)
- Aravind Cherukuri
- Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh, PA, USA
| | - David M. Rothstein
- Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh, PA, USA
- Department of Immunology, University of Pittsburgh, PA, USA
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22
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Vanhove T, Elias N, Safa K, Cohen-Bucay A, Schold JD, Riella LV, Gilligan H. Long-term outcome reporting in older kidney transplant recipients and the limitations of conventional survival metrics. Kidney Int Rep 2022; 7:2397-2409. [DOI: 10.1016/j.ekir.2022.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 08/14/2022] [Accepted: 08/15/2022] [Indexed: 11/30/2022] Open
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23
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Mayer KA, Budde K, Jilma B, Doberer K, Böhmig GA. Emerging drugs for antibody-mediated rejection after kidney transplantation: a focus on phase II & III trials. Expert Opin Emerg Drugs 2022; 27:151-167. [PMID: 35715978 DOI: 10.1080/14728214.2022.2091131] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Its therapy continues to be challenge, and no treatment has been approved for the market thus far. AREAS COVERED In this article, we discuss the pathophysiology and phenotypic presentation of ABMR, the current level of evidence to support the use of available therapeutic strategies, and the emergence of tailored drugs now being evaluated in systematic clinical trials. We searched PubMed, Clinicaltrials.gov and Citeline's Pharmaprojects for pertinent information on emerging anti-rejection strategies, laying a focus on phase II and III trials. EXPERT OPINION Currently, we rely on the use of apheresis for alloantibody depletion and intravenous immunoglobulin (referred to as standard of care), preferentially in early active ABMR. Recent systematic trials have questioned the benefits of using the CD20 antibody rituximab or the proteasome inhibitor bortezomib. However, there are now several promising treatment approaches in the pipeline, which are being trialed in phase II and III studies. These include interleukin-6 antagonism, CD38-targeting antibodies, and selective inhibitors of complement. On the basis of the information that has emerged so far, it seems that innovative treatment strategies for clinical use in ABMR may be available within the next 5-10 years.
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Affiliation(s)
- Katharina A Mayer
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Klemens Budde
- Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Bernd Jilma
- Department of Clinical Pharmacology, Medical University of Vienna, Austria
| | - Konstantin Doberer
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Georg A Böhmig
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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24
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Kidney Retransplantation after Graft Failure: Variables Influencing Long-Term Survival. J Transplant 2022; 2022:3397751. [PMID: 35782455 PMCID: PMC9242806 DOI: 10.1155/2022/3397751] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/13/2022] [Indexed: 12/02/2022] Open
Abstract
Background There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan–Meier method, and risk factors were identified using multiple Cox regression. Results We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, p=0.104) but an inferior graft survival thereafter (log-rank p=0.026). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson–Deyo index, active smoking, and life-threatening complications (Clavien–Dindo grade IV) at first transplantation. Conclusion Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible.
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25
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Naesens M, Loupy A, Hilbrands L, Oberbauer R, Bellini MI, Glotz D, Grinyó J, Heemann U, Jochmans I, Pengel L, Reinders M, Schneeberger S, Budde K. Rationale for Surrogate Endpoints and Conditional Marketing Authorization of New Therapies for Kidney Transplantation. Transpl Int 2022; 35:10137. [PMID: 35669977 PMCID: PMC9163307 DOI: 10.3389/ti.2022.10137] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 03/10/2022] [Indexed: 12/13/2022]
Abstract
Conditional marketing authorization (CMA) facilitates timely access to new drugs for illnesses with unmet clinical needs, such as late graft failure after kidney transplantation. Late graft failure remains a serious, burdensome, and life-threatening condition for recipients. This article has been developed from content prepared by members of a working group within the European Society for Organ Transplantation (ESOT) for a Broad Scientific Advice request, submitted by ESOT to the European Medicines Agency (EMA), and reviewed by the EMA in 2020. The article presents the rationale for using surrogate endpoints in clinical trials aiming at improving late graft failure rates, to enable novel kidney transplantation therapies to be considered for CMA and improve access to medicines. The paper also provides background data to illustrate the relationship between primary and surrogate endpoints. Developing surrogate endpoints and a CMA strategy could be particularly beneficial for studies where the use of primary endpoints would yield insufficient statistical power or insufficient indication of long-term benefit following transplantation.
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Affiliation(s)
- Maarten Naesens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- *Correspondence: Maarten Naesens,
| | - Alexandre Loupy
- Paris Translational Research Center for Organ Transplantation, Hôpital Necker, Paris, France
| | - Luuk Hilbrands
- Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Rainer Oberbauer
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | | | - Denis Glotz
- Paris Translational Research Center for Organ Transplantation, Hôpital Saint Louis, Paris, France
| | | | - Uwe Heemann
- Department of Nephrology, Technical University of Munich, Munich, Germany
| | - Ina Jochmans
- Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Liset Pengel
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Marlies Reinders
- Erasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Stefan Schneeberger
- Department of General, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
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26
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Sageshima J, Chandar J, Chen LJ, Shah R, Al Nuss A, Vincenzi P, Morsi M, Figueiro J, Vianna R, Ciancio G, Burke GW. How to Deal With Kidney Retransplantation-Second, Third, Fourth, and Beyond. Transplantation 2022; 106:709-721. [PMID: 34310100 DOI: 10.1097/tp.0000000000003888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.
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Affiliation(s)
- Junichiro Sageshima
- Division of Transplant Surgery, Department of Surgery, University of California Davis School of Medicine, Sacramento, CA
| | - Jayanthi Chandar
- Division of Pediatric Kidney Transplantation, Department of Pediatrics, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Linda J Chen
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Rushi Shah
- Surgical Transplant Fellow, Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Ammar Al Nuss
- Surgical Transplant Fellow, Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Paolo Vincenzi
- Surgical Transplant Fellow, Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Mahmoud Morsi
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Jose Figueiro
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Rodrigo Vianna
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
- Division of Liver and GI Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Gaetano Ciancio
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
| | - George W Burke
- Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL
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27
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Knoll G, Campbell P, Chasse M, Fergusson D, Ramsay T, Karnabi P, Perl J, House A, Kim J, Johnston O, Mainra R, Houde I, Baran D, Treleaven D, Senecal L, Tibbles LA, Hébert MJ, White C, Karpinski M, Gill J. Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multi-Center Canadian Cohort Study. J Am Soc Nephrol 2022; 33:1182-1192. [PMID: 35321940 PMCID: PMC9161795 DOI: 10.1681/asn.2021121642] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 01/01/2023] Open
Abstract
Background: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. Methods: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and panel reactive anti-HLA antibodies (PRA) were determined at 1, 3, 6 , and 12 months and bi-annually until death, repeat transplantation, or loss to follow-up. Results: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, while 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (HR =0.40, 95% CI, 0.17-0.93) and were not at increased risk of hospitalized infection (HR 1.81; 95% CI 0.82 to 4.0) compared to patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II PRA increased from 11% to 27% and 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR 0.81, 95% CI, 0.22-2.94). Conclusions: Prolonged use of immunosuppressants greater than one year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.
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Affiliation(s)
- Greg Knoll
- G Knoll, Department of Medicine (Nephrology), University of Ottawa, Ottawa, Canada
| | - Patrica Campbell
- P Campbell, Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Canada
| | - Michael Chasse
- M Chasse, Department of Medicine (Critical Care), University of Montreal Hospital Centre, Montreal, Canada
| | - Dean Fergusson
- D Fergusson, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
| | - Tim Ramsay
- T Ramsay, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada
| | - Priscilla Karnabi
- P Karnabi, Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
| | - Jeffrey Perl
- J Perl, Division of Nephrology, St Michael's Hospital, Toronto, Canada
| | - Andrew House
- A House, Department of Medicine (Nephrology), Western University, London, Canada
| | - Joe Kim
- J Kim, Institute of Health Policy, Management and Evaluation, University of Toronto Dalla Lana School of Public Health, Toronto, Canada
| | - Olwyn Johnston
- O Johnston, Division of Nephrology, The University of British Columbia, Vancouver, Canada
| | - Rahul Mainra
- R Mainra, Saskatchewan Transplant Program, Department of Medicine, University of Saskatchewan, Saskatoon, Canada
| | - Isabel Houde
- I Houde , Transplantation Unit, Renal Division, Department of Medicine, Laval University Faculty of Medicine, Quebec, Canada
| | - Dana Baran
- D Baran, Division of Nephrology and the Multi Organ Transplant Program, Royal Victoria Hospital, Montreal, Canada
| | - Darin Treleaven
- D Treleaven, Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada
| | - Lynne Senecal
- L Senecal, Department of Nephrology, Maisonneuve-Rosemont Hospital, Montreal, Canada
| | - Lee Ann Tibbles
- L Tibbles, ALTRA Transplant Program, Southern Alberta, Department of Medicine, University of Calgary, Calgary, Canada
| | - Marie-Josée Hébert
- M Hébert, Centre de recherche, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
| | - Christine White
- C White, Department of Medicine, Queen's University, Kingston, Canada
| | - Martin Karpinski
- M Karpinski, Department of Medicine, University of Manitoba, Winnipeg, Canada
| | - John Gill
- J Gill, Division of Nephrology, The University of British Columbia, Vancouver, Canada
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28
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Nasic S, Mölne J, Stegmayr B, Peters B. Histological diagnosis from kidney transplant biopsy can contribute to prediction of graft survival. Nephrology (Carlton) 2022; 27:528-536. [PMID: 35150598 PMCID: PMC9302625 DOI: 10.1111/nep.14028] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 11/29/2022]
Abstract
Aim The primary aim of this study was to in depth examine if the histological findings in a transplanted kidney biopsy can predict the prognosis for the graft and the patient. The secondary aim was to extend knowledge of the impact of time elapsed on biopsy findings. Methods Data from 1462 patients were merged from a kidney transplantation registry and a biopsy registry during 1 January 2007 and 30 September 2017. Kaplan–Meier analysis and multivariate Cox‐regression analysis were performed and hazard ratios (HR) with 95% confidence intervals (CI) were presented. Results Compared to normal biopsy findings, graft survival after biopsy (gsaBiopsy) was shorter for patients with glomerular diseases (HR 8.2, CI:3.2–21.1), rejections (HR 4.2, CI:1.7–10.3), chronic changes including IFTA (HR 3.2, CI:1.3–8.0), acute tubular injuries (HR 3.0, CI:1.2–7.8), and borderline changes (HR 2.9, CI:1.1–7.6). Sub‐analysis of rejections showed shorter gsaBiopsy for chronic TCMR (HR 4.7, CI:1.9–11.3), active ABMR (HR 3.6, CI:1.7–7.7) and chronic ABMR (HR 3.5, CI:2.0–6.0). Patients with TCMR Banff grade II (HR 0.35, CI:0.20–0.63) and grade I (HR 0.52, CI:0.29–0.93) had a better gsaBiopsy compared to all other types of rejections. Conclusion Shorter gsaBiopsy was noted in kidneys with glomerular diseases, rejections, acute tubular injuries and borderline changes. TCMR Banff rejections grade I and II were associated with a better prognosis. This Swedish single centre study showed that the impact on allograft survival is dependent on the nature of the biopsy findings, with histological findings of glomerular disease, severe rejections and chronic changes being associated with more rapid allograft loss.
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Affiliation(s)
- Salmir Nasic
- Research and Development Centre at Skaraborg Hospital, Skövde, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Johan Mölne
- Institute of Biomedicine, Laboratory Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Bernd Stegmayr
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Björn Peters
- Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.,Nephrology, Skaraborg Hospital, Skövde, Sweden
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29
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Nardelli L, Scalamogna A, Messa P, Gallieni M, Cacciola R, Tripodi F, Castellano G, Favi E. Peritoneal Dialysis for Potential Kidney Transplant Recipients: Pride or Prejudice? MEDICINA (KAUNAS, LITHUANIA) 2022; 58:214. [PMID: 35208541 PMCID: PMC8875254 DOI: 10.3390/medicina58020214] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/24/2022] [Accepted: 01/29/2022] [Indexed: 12/28/2022]
Abstract
Kidney transplantation (KT) is recognized as the gold-standard of treatment for patients with end-stage renal disease. Additionally, it has been demonstrated that receiving a pre-emptive KT ensures the best recipient and graft survivals. However, due to an overwhelming discrepancy between the organs available and the patients on the transplant waiting list, the vast majority of transplant candidates require prolonged periods of dialysis before being transplanted. For many years, peritoneal dialysis (PD) and hemodialysis (HD) have been considered competitive renal replacement therapies (RRT). This dualistic vision has recently been questioned by evidence suggesting that an individualized and flexible approach may be more appropriate. In fact, tailored and cleverly planned changes between different RRT modalities, according to the patient's needs and characteristics, are often needed in order to achieve the best results. While home HD is still under scrutiny in this particular setting, current data seems to favor the use of PD over in-center HD in patients awaiting a KT. In this specific population, the demonstrated advantages of PD are superior quality of life, longer preservation of residual renal function, lower incidence of delayed graft function, better recipient survival, and reduced cost.
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Affiliation(s)
- Luca Nardelli
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.N.); (A.S.); (P.M.); (F.T.); (G.C.)
| | - Antonio Scalamogna
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.N.); (A.S.); (P.M.); (F.T.); (G.C.)
| | - Piergiorgio Messa
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.N.); (A.S.); (P.M.); (F.T.); (G.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Maurizio Gallieni
- Department of Biomedical and Clinical Sciences, Università di Milano, 20157 Milan, Italy;
- Nephrology and Dialysis Unit, ASST Fatebenefratelli Sacco, 20157 Milan, Italy
| | - Roberto Cacciola
- Department of Surgical Sciences, Università di Tor Vergata, 00133 Rome, Italy;
| | - Federica Tripodi
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.N.); (A.S.); (P.M.); (F.T.); (G.C.)
| | - Giuseppe Castellano
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.N.); (A.S.); (P.M.); (F.T.); (G.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Evaldo Favi
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
- Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
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Hussain A, Culliford A, Phagura N, Evison F, Gallier S, Sharif A. Comparing survival outcomes for kidney transplant recipients with pre-existing diabetes versus those who develop post-transplantation diabetes. Diabet Med 2022; 39:e14707. [PMID: 34599527 DOI: 10.1111/dme.14707] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 09/09/2021] [Accepted: 09/29/2021] [Indexed: 01/13/2023]
Abstract
INTRODUCTION The aim of this study was to compare the management strategy and clinical outcomes for kidney transplant recipients with pre-transplant versus post-transplantation diabetes (PTDM) in a contemporary cohort. METHODS This is a single-centre, retrospective. observational study of kidney transplant recipients between 2007 and 2018 with follow-up to 31 December 2020. Data were extracted from hospital electronic patient records, with clinical outcomes linked to national data sets. PTDM was diagnosed by international consensus guidelines. Unadjusted and adjusted survival outcomes were assessed with Kaplan-Meier curves and Cox regression models, respectively, with PTDM handled as a time-varying covariate. RESULTS Data were analysed for 1,757 kidney transplant recipients, of whom 11.8% (n = 207) had pre-transplant diabetes, and 13.8% (n = 243) developed PTDM with median time to onset 108 days (IQR 46-549 days). Median follow-up was 1,839 days (IQR 928-2985 days). Disparate management strategies were observed, although insulin was the commonest glucose-lowering therapy for all patients with diabetes. In adjusted models, PTDM was associated with lower mortality (HR 0.663, 95% CI 0.543-0.810) and pre-diabetes with higher mortality (HR 1.675, 95% CI 1.396-2.011). However, if analyses are restricted to those with at least 5-year follow-up, then PTDM has no association with mortality (HR 0.771, 95% CI 0.419-1.096), but pre-transplant diabetes remains associated with higher mortality (HR 2.029, 95% CI 1.367-3.012). CONCLUSIONS Pre-transplant diabetes remains associated with increased mortality risk after kidney transplantation, but PTDM effects are time dependent. Development of PTDM should be encouraged as a mandated registry return to study the long-term impact on survival outcomes.
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Affiliation(s)
- Azm Hussain
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK
| | - Alice Culliford
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK
| | - Nuvreen Phagura
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Felicity Evison
- Department of Health Informatics, University Hospitals Birmingham, Birmingham, UK
| | - Suzy Gallier
- Department of Health Informatics, University Hospitals Birmingham, Birmingham, UK
- PIONEER: HDR-UK hub in Acute Care, University of Birmingham, Birmingham, UK
| | - Adnan Sharif
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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31
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Fusfeld L, Menon S, Gupta G, Lawrence C, Masud SF, Goss TF. US payer budget impact of a microarray assay with machine learning to evaluate kidney transplant rejection in for-cause biopsies. J Med Econ 2022; 25:515-523. [PMID: 35345966 DOI: 10.1080/13696998.2022.2059221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
AIM This study evaluates the economic impact to US commercial payers of MMDx-Kidney used in conjunction with histologic evaluation of for-cause kidney transplant biopsies. MATERIALS AND METHODS An Excel-based model was developed to assess the cost impact of histology plus MMDx-Kidney versus histology alone for the evaluation of potential rejection in kidney transplant patients who receive a for-cause biopsy. Different model time periods were assessed, ranging from 1 to 5 years post-biopsy. A targeted literature review was used to identify parameter estimates, validated by two external clinicians with expertise in managing kidney transplant rejection. A sensitivity analysis was conducted to evaluate the relative impact of key clinical and cost parameters. In particular, the model identified the magnitude of MMDx-Kidney's impact on graft failure from rejection that would be required for MMDx-Kidney to be cost-neutral. RESULTS By more accurately characterizing rejection, MMDx-Kidney is estimated to increase antirejection treatment costs by $1,126 per test. Nevertheless, a break-even analysis shows that the costs of MMDx-Kidney and anti-rejection medication, as well as the costs associated with an increase in the number of patients with functioning transplants, may be offset by reductions in costs associated with graft failure (i.e. costs of hospitalizations, dialysis, and repeat transplants) over 5 years, assuming MMDx-Kidney reduces annual graft failure from rejection by at least 5%. For the base case, with a 25% relative reduction in annual rate of graft failures from rejection, MMDx-Kidney increases overall costs incurred in the first year of the model but starts generating savings by the second year of the model. CONCLUSIONS Compared with histologic evaluation of for-cause kidney transplant biopsies alone, the use of MMDx-Kidney in conjunction with histologic evaluation improves the diagnoses of graft dysfunction and may have the potential to generate overall savings from reductions in rejection-related graft failure.
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Affiliation(s)
- Lauren Fusfeld
- Boston Healthcare Associates, Inc. (now a Veranex company), Boston, MA, USA
| | - Sreeranjani Menon
- Boston Healthcare Associates, Inc. (now a Veranex company), Boston, MA, USA
| | - Gaurav Gupta
- Division of Nephrology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | | | - Salwa F Masud
- Boston Healthcare Associates, Inc. (now a Veranex company), Boston, MA, USA
| | - Thomas F Goss
- Boston Healthcare Associates, Inc. (now a Veranex company), Boston, MA, USA
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32
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Taira H, Noguchi H, Ueki K, Kaku K, Tsuchimoto A, Okabe Y, Ohya Y, Nakamura M. Initiation of dialysis for kidney graft failure: A retrospective single-center cohort study. Ther Apher Dial 2021; 26:806-814. [PMID: 34779578 DOI: 10.1111/1744-9987.13756] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 04/22/2021] [Accepted: 10/26/2021] [Indexed: 11/30/2022]
Abstract
Few studies have focused on the outcome of dialysis for kidney graft failure. We investigated the outcomes of dialysis for graft failure. We retrospectively studied 52 patients undergoing dialysis for graft failure at our facility from January 2004 to December 2018. The mean age at initiation of dialysis was 51.8 ± 13.5 years. The patient survival rates after initiation of dialysis at 1, 3, and 5 years were 96.0%, 93.8%, and 82.4%, respectively. The rate of unplanned initiation was 44.2%. In multivariate logistic analysis, lack of follow-up by nephrologists and pre-emptive kidney transplantation (PEKT) tended to be risk factors for unplanned initiation (P = 0.065 and P = 0.014, respectively). Our study suggests that the prognosis of patients with dialysis for graft failure is acceptable. Dialysis for graft failure, especially in patients with PEKT, tends to be unplanned, and for safe initiation, early involvement of nephrologists may be necessary.
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Affiliation(s)
- Hirona Taira
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan
| | - Hiroshi Noguchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenji Ueki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keizo Kaku
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yusuke Ohya
- Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Vlachopanos G, El Kossi M, Aziz D, Halawa A. Association of Nephrectomy of the Failed Renal Allograft With Outcome of the Future Transplant: A Systematic Review. EXP CLIN TRANSPLANT 2021; 20:1-11. [PMID: 34775942 DOI: 10.6002/ect.2021.0133] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Kidney allograft failure is a significant complication in kidney transplant recipients, and the surgical decision to perform allograft nephrectomy poses a strong dilemma because it is associated with significant morbidity and mortality. There is a debate over the effect of allograft nephrectomy on the development of allosensitization and the impact on potential retransplantation. Moreover, the use of immunosuppression may contribute to antibody allosensitization as allograft nephrectomy and immunosuppression act jointly and interdependently toward antibody formation. Because more and more patients with kidney allograft failure are entering wait lists for repeat transplant procedures, a review of available evidence on the field is required. Here, we performed a literature search using multiple medical databases to identify relevant studies that assessed the effects of allograft nephrectomy on important retransplant endpoints such as allograft and patient survival; furthermore, secondary outcomes such as alloantibody sensitization were also evaluated. A total of 15 studies were identified; all were retrospective, single-center studies. The rate of allograft nephrectomy in patients with retransplant varied widely (from 20% to 80%). The average allograft nephrectomy rate in included studies was 43% (allograft nephrectomy number/number of repeat transplantations: 2351/5431). Most studies did not observe an allograft survival benefit after retransplant for patients with allograft nephrectomy with the exception of 4 studies that found worse allograft survival after allograft nephrectomy. Interestingly, 1 study found that, in the patient subgroup with early kidney allograft failure (<12 months posttransplant), allograft nephrectomy may be associated with better allograft survival. Available data suggested that allograft nephrectomy may be associated with a higher risk of increasing anti-HLA antibody levels. The quality of the included studies suffered from nonrandomized design, potential confounding, and small sample size. To conclude, further randomized controlled trials are required to delineate the role of allograft nephrectomy on retransplant outcomes.
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Affiliation(s)
- Georgios Vlachopanos
- From the Department of Nephrology, General Hospital of Nikea, Athens, Greece.,From the School of Medicine, Institute of Life Course and Medical Sciences, Faculty of Health and Science, University of Liverpool, Liverpool, United Kingdom
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Díez-Sanmartín C, Sarasa-Cabezuelo A, Andrés Belmonte A. The impact of artificial intelligence and big data on end-stage kidney disease treatments. EXPERT SYSTEMS WITH APPLICATIONS 2021; 180:115076. [DOI: 10.1016/j.eswa.2021.115076] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
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Atique M, Ghafoor A, Javed R, Fatima N, Yousaf A, Zahra S. Correlation of Viral Load With the Clinical and Biochemical Profiles of COVID-19 Patients. Cureus 2021; 13:e16655. [PMID: 34462686 PMCID: PMC8388060 DOI: 10.7759/cureus.16655] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2021] [Indexed: 12/15/2022] Open
Abstract
Background/objective Coronavirus infectious disease (COVID-19) is a novel disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Some studies have shown that disease severity according to clinical and biochemical parameters are in direct relation to viral load while others have found no direct correlation. In this study, the COVID-19 cycle threshold (Ct) value, which is taken as a direct indicator of the viral load, has been correlated with the biochemical and clinical parameters in COVID-19 patients. Methods In this cross-sectional, retrospective, and single-center study, 365 patients admitted with COVID 19 were divided into three groups according to their Ct values obtained from reverse transcription-polymerase chain reaction RT-PCR as 1 (9-20), 2 (21-30), and 3 (31-40). The correlation of the COVID-19 Ct value with biochemical parameters and clinical presentation (taken as mild, moderate, and severe) was done and analyzed. The chi-square test was used for the correlation and calculated by using SPSS V-24.0 (IBM Corp., Armonk, NY). p-value <0.05 was considered significant statistically. Results Disease severity levels (mild, moderate, and severe) correlated in group 1 (Ct value 9 to 20), 2 (Ct value 21 to 30), and 3 (Ct value 31 to 40) but no significance was found between disease severity levels and the Ct value groups' p-value (>0.05). All the biochemical parameters analyzed (alanine transaminase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, c-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, D-dimer, and total leucocyte count (TLC)) showed a significant p-value (<0.05) in all the three groups studied. Procalcitonin (PCT), however, did not show any significant value in any of the groups studied. In the intergroup assessment, it was found that the values of ALT, AST, albumin, CRP, ferritin, bilirubin, and TLC are maximum in group 2 with a downward trend in groups 1 and 2. Neutrophils and lymphocytes did not show any variations. LDH did not follow the trend of increasing viral load. Conclusions The severity of the disease was not statistically significant in the Ct value groups (p> 0.05). However biochemical parameters, i.e. ALT, AST, ALP, CRP, and bilirubin were statistically significant (p<0.05). Patients with COVID-19 should be closely monitored for the assessment of disease progression according to the above-mentioned biochemical parameters.
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Affiliation(s)
- Muhammad Atique
- Histopathology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
| | - Atif Ghafoor
- Molecular Biology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
| | - Rabia Javed
- Histopathology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
| | - Noor Fatima
- Molecular Biology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
| | - Anam Yousaf
- Molecular Biology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
| | - Samana Zahra
- Molecular Biology, Pakistan Kidney and Liver Institute & Research Center, Lahore, PAK
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Lubetzky M, Tantisattamo E, Molnar MZ, Lentine KL, Basu A, Parsons RF, Woodside KJ, Pavlakis M, Blosser CD, Singh N, Concepcion BP, Adey D, Gupta G, Faravardeh A, Kraus E, Ong S, Riella LV, Friedewald J, Wiseman A, Aala A, Dadhania DM, Alhamad T. The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients. Am J Transplant 2021; 21:2937-2949. [PMID: 34115439 DOI: 10.1111/ajt.16717] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/23/2021] [Accepted: 05/20/2021] [Indexed: 01/25/2023]
Abstract
The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.
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Affiliation(s)
- Michelle Lubetzky
- Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Ekamol Tantisattamo
- Division of Nephrology, University of California Irvine, Orange, California, USA
| | - Miklos Z Molnar
- Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah, USA
| | - Krista L Lentine
- Internal Medicine-Nephrology, Saint Louis University, St. Louis, Missouri, USA
| | - Arpita Basu
- Division of Transplantation, Emory University, Atlanta, Georgia, USA
| | - Ronald F Parsons
- Division of Transplantation, Emory University, Atlanta, Georgia, USA
| | - Kenneth J Woodside
- Department of Surgery, Section of Transplantation, University of Michigan, Ann Arbor, Michigan, USA
| | - Martha Pavlakis
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Christopher D Blosser
- Division of Nephrology, University of Washington and Seattle Children's Hospital, Seattle, Washington, USA
| | - Neeraj Singh
- Division of Nephrology, Willis Knighton Health System, Shreveport, Louisiana, USA
| | | | - Deborah Adey
- Division of Nephrology, University of California San Francisco, San Francisco, California, USA
| | - Gaurav Gupta
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Arman Faravardeh
- SHARP Kidney and Pancreas Transplant Center, San Diego, California, USA
| | - Edward Kraus
- Department of Medicine, Johns Hopkins, Baltimore, Maryland, USA
| | - Song Ong
- Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Leonardo V Riella
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - John Friedewald
- Division of Medicine and Surgery, Northwestern University, Chicago, Illinois, USA
| | - Alex Wiseman
- Division of Nephrology, University of Colorado, Denver, Colorado, USA
| | - Amtul Aala
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Darshana M Dadhania
- Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Tarek Alhamad
- Division of Nephrology, Washington University in St. Louis, St. Louis, Michigan, USA
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Codina S, Manonelles A, Tormo M, Sola A, Cruzado JM. Chronic Kidney Allograft Disease: New Concepts and Opportunities. Front Med (Lausanne) 2021; 8:660334. [PMID: 34336878 PMCID: PMC8316649 DOI: 10.3389/fmed.2021.660334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic kidney disease (CKD) is increasing in most countries and kidney transplantation is the best option for those patients requiring renal replacement therapy. Therefore, there is a significant number of patients living with a functioning kidney allograft. However, progressive kidney allograft functional deterioration remains unchanged despite of major advances in the field. After the first post-transplant year, it has been estimated that this chronic allograft damage may cause a 5% graft loss per year. Most studies focused on mechanisms of kidney graft damage, especially on ischemia-reperfusion injury, alloimmunity, nephrotoxicity, infection and disease recurrence. Thus, therapeutic interventions focus on those modifiable factors associated with chronic kidney allograft disease (CKaD). There are strategies to reduce ischemia-reperfusion injury, to improve the immunologic risk stratification and monitoring, to reduce calcineurin-inhibitor exposure and to identify recurrence of primary renal disease early. On the other hand, control of risk factors for chronic disease progression are particularly relevant as kidney transplantation is inherently associated with renal mass reduction. However, despite progress in pathophysiology and interventions, clinical advances in terms of long-term kidney allograft survival have been subtle. New approaches are needed and probably a holistic view can help. Chronic kidney allograft deterioration is probably the consequence of damage from various etiologies but can be attenuated by kidney repair mechanisms. Thus, besides immunological and other mechanisms of damage, the intrinsic repair kidney graft capacity should be considered to generate new hypothesis and potential therapeutic targets. In this review, the critical risk factors that define CKaD will be discussed but also how the renal mechanisms of regeneration could contribute to a change chronic kidney allograft disease paradigm.
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Affiliation(s)
- Sergi Codina
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Anna Manonelles
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
| | - Maria Tormo
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Anna Sola
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Josep M. Cruzado
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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Rodríguez-Espinosa D, Broseta JJ, Hermida E, Cuadrado E, Guillén-Olmos E, Montagud-Marrahi E, Diekmann F. Rapid re-transplantation safety following early kidney graft loss. Nephrology (Carlton) 2021; 26:742-747. [PMID: 34051132 DOI: 10.1111/nep.13907] [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: 03/13/2021] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Early graft loss is a devastating kidney transplant complication associated with high mortality and an increased risk of sensitization to antigens from the failed graft. Moreover, if rapid re-transplantation were to occur, given that the human leukocyte antigen antibodies identification may not be reliable until several weeks after transplantation, the recipient's immunological status would be uncertain. Hence, there could be an increased immunological risk. To date, there is no information on whether a rapid re-transplantation after early graft loss, without a new reliable anti-HLA determination, is safe. METHODS We retrospectively analysed the number of rejections and the graft survival of re-transplanted patients with early graft loss (defined as graft failure before 30 days from transplant) from our centre between June 2003 and November 2019. The studied population was divided into rapid re-transplantation (performed within 30 days of early graft loss) and late re-transplantation (performed beyond those 30 days). RESULTS Forty-seven patients were re-transplanted after early graft loss. There were nine rapid re-transplantation cases with an 89% five-year graft survival and one antibody-mediated rejection episode. Furthermore, we identified 38 cases of late re-transplantation with a 69% five-year graft survival, 4 T cell-mediated, and 11 antibody-mediated rejections. CONCLUSIONS Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor does it impact long-term graft survival when compared to late re-transplantation.
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Affiliation(s)
- Diana Rodríguez-Espinosa
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - José Jesús Broseta
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Evelyn Hermida
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Elena Cuadrado
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Elena Guillén-Olmos
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Enrique Montagud-Marrahi
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain.,Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Red de Investigación Renal (REDINREN), Madrid, Spain
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Blosser CD, Haber G, Engels EA. Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period. Kidney Int 2021; 99:1430-1438. [PMID: 33159960 PMCID: PMC8096865 DOI: 10.1016/j.kint.2020.10.018] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 09/26/2020] [Accepted: 10/01/2020] [Indexed: 02/08/2023]
Abstract
Recipients of kidney transplants have elevated cancer risk compared with the general population. Improvements over time in transplant care and cancer treatment may have affected incidence and outcomes of cancer among recipients of kidney transplant. To evaluate this, we used linked United States transplant and cancer registry data to study 101,014 adult recipients of kidney transplants over three decades (1987-1996, 1997-2006, 2007-2016). Poisson regression was used to assess trends in incidence for cancer overall and seven common cancers. Associations of cancer with risk of death-censored graft failure (DCGF) and death with functioning graft (DWFG) were evaluated with Cox regression. We also estimated absolute risks of DCGF and graft failure following cancer for recipients transplanted in 2007-2016. There was no significant change in the incidence of cancer overall or for six common cancers in recipients across the 1987-2016 period. Only the incidence of prostate cancer significantly decreased across this period after multivariate adjustment. Among recipients of kidney transplants with non-Hodgkin lymphoma, there were significant declines over time in elevated risks for DCGF and DWFG but no significant changes for other combined cancers. For recipients transplanted in the most recent period (2007-2016), risks following cancer diagnosis remained high, with 38% experiencing DWFG and 14% graft failure within four years of diagnosis. Absolute risk of DWFG was especially high following lung cancer (78%), non-Hodgkin lymphoma (38%), melanoma (35%), and colorectal cancer (49%). Thus, across a 30-year period in the United States, there was no overall change in cancer incidence among recipients of kidney transplants. Despite improvements for non-Hodgkin lymphoma, cancer remains a major cause of morbidity and mortality.
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Affiliation(s)
- Christopher D Blosser
- Department of Medicine, University of Washington and Seattle Children's Hospital, Seattle, Washington, USA
| | - Gregory Haber
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
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40
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Meng X, Wu W, Xu S, Cheng Z. Comparison of outcomes of peritoneal dialysis between patients after failed kidney transplant and transplant-naïve patients: a meta-analysis of observational studies. Ren Fail 2021; 43:698-708. [PMID: 33896379 PMCID: PMC8079072 DOI: 10.1080/0886022x.2021.1914659] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
PURPOSE The influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation. METHODS We searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR). RESULTS We included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80-1.61; I2=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97-1.32; I2=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67-1.50; I2=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88-1.78; I2=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72-1.50; I2=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77-2.00; I2=66%; p = 0.38] between the study groups. CONCLUSION Patients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.
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Affiliation(s)
- Xiaohua Meng
- Department of Nephrology, Huzhou Central Hospital, Affiliated Central Hospital of HuZhou University, Huzhou, Zhejiang Province, P.R. China
| | - Weifei Wu
- Department of Nephrology, Huzhou Central Hospital, Affiliated Central Hospital of HuZhou University, Huzhou, Zhejiang Province, P.R. China
| | - Shuang Xu
- Department of Nephrology, Huzhou Central Hospital, Affiliated Central Hospital of HuZhou University, Huzhou, Zhejiang Province, P.R. China
| | - Zhiqun Cheng
- Department of Nephrology, Huzhou Central Hospital, Affiliated Central Hospital of HuZhou University, Huzhou, Zhejiang Province, P.R. China
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41
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Rahimishahmirzadi M, Jevnikar AM, House AA, Luke PP, Humar A, Silverman MS, Shalhoub SM, Hosseini-Moghaddam SM. Late-onset allograft rejection, cytomegalovirus infection, and renal allograft loss: Is anti-CMV prophylaxis required following late-onset allograft rejection? Clin Transplant 2021; 35:e14285. [PMID: 33713374 DOI: 10.1111/ctr.14285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/09/2021] [Accepted: 03/08/2021] [Indexed: 11/29/2022]
Abstract
Renal transplant recipients remain at risk of delayed-onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early-vs late-onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long-term allograft outcome. Median (IQR) duration of follow-up was 1186.0 (904.7-1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R- CMV serostatus (OR: 5.5, 95% CI: 2.5-12.2) and LAR (OR: 7.9, 95% CI: 2.8-22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed-onset CMV infection (HR: 2.51, 95% CI: 1.08-5.86) and LAR (HR: 5.46, 95% CI: 2.26-13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late-onset CMV infection. Post-LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.
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Affiliation(s)
| | - Anthony M Jevnikar
- Multiorgan Transplant Program, London Health Sciences Centre, Western University, London, ON, Canada
| | - Andrew A House
- Multiorgan Transplant Program, London Health Sciences Centre, Western University, London, ON, Canada
| | - Patrick P Luke
- Multiorgan Transplant Program, London Health Sciences Centre, Western University, London, ON, Canada
| | - Atul Humar
- Division of Infectious Diseases, Transplant Infectious Diseases Program, University Health Network, Toronto, ON, Canada.,Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Michael S Silverman
- Division of Infectious Diseases, Department of Medicine, Western University, London, ON, Canada
| | - Sarah M Shalhoub
- Multiorgan Transplant Program, London Health Sciences Centre, Western University, London, ON, Canada.,Division of Infectious Diseases, Department of Medicine, Western University, London, ON, Canada
| | - Seyed M Hosseini-Moghaddam
- Multiorgan Transplant Program, London Health Sciences Centre, Western University, London, ON, Canada.,Division of Infectious Diseases, Department of Medicine, Western University, London, ON, Canada.,Division of Infectious Diseases, Transplant Infectious Diseases Program, University Health Network, Toronto, ON, Canada.,Department of Medicine, University of Toronto, Toronto, ON, Canada
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Han F, Sun Q, Huang Z, Li H, Ma M, Liao T, Luo Z, Zheng L, Zhang N, Chen N, Hong L, Na N, Sun Q. Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients. Aging (Albany NY) 2021; 13:8440-8453. [PMID: 33714205 PMCID: PMC8034952 DOI: 10.18632/aging.202654] [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: 11/13/2020] [Accepted: 01/22/2021] [Indexed: 11/25/2022]
Abstract
We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p<0.001). Multivariate logistic regression analysis showed that dmtDNA levels were also significantly associated with AR (OR=1.588, 95% CI 1.337-4.561, p<0.001). When the dmtDNA level was >0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.
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Affiliation(s)
- Fei Han
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Qipeng Sun
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhengyu Huang
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Heng Li
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Maolin Ma
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Tao Liao
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zihuang Luo
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Lingling Zheng
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Nana Zhang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Nan Chen
- Laboratory of Cancer Biomarkers and Liquid Biopsy, Henan University, Kaifeng, China
| | - Liangqing Hong
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ning Na
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Qiquan Sun
- Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Arnau A, Benito-Hernández A, Ramos-Barrón MA, García-Unzueta MT, Gómez-Román JJ, Gómez-Ortega JM, López-Hoyos M, San Segundo D, Ruiz JC, Rodrigo E. Urinary C-X-C Motif Chemokine 10 Is Related to Acute Graft Lesions Secondary to T Cell- and Antibody-Mediated Damage. Ann Transplant 2021; 26:e929491. [PMID: 33686050 PMCID: PMC7955576 DOI: 10.12659/aot.929491] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-γ-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. Material/Methods A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. Results Banff scores ‘t’, ‘i’, ‘g’, and ‘ptc’ were significantly related to urinary CXCL10 levels. Multivariate analysis showed that ‘t’ (β=0.107, P=0.001) and ‘ptc’ (β=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799–11.646, P=0.001) after multivariate regression analysis. Conclusions DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.
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Affiliation(s)
- Alvaro Arnau
- Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - Adalberto Benito-Hernández
- Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - María Angeles Ramos-Barrón
- Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - María Teresa García-Unzueta
- Department of Clinical Biochemistry, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - José Javier Gómez-Román
- Pathology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - José María Gómez-Ortega
- Pathology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - Marcos López-Hoyos
- Immunology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - David San Segundo
- Immunology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - Juan Carlos Ruiz
- Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
| | - Emilio Rodrigo
- Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain
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Schrezenmeier E, Lehner LJ, Merkel M, Mayrdorfer M, Duettmann W, Naik MG, Fröhlich F, Liefeldt L, Pigorsch M, Friedersdorff F, Schmidt D, Niemann M, Lachmann N, Budde K, Halleck F. What happens after graft loss? A large, long-term, single-center observation. Transpl Int 2021; 34:732-742. [PMID: 33527467 DOI: 10.1111/tri.13834] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/01/2020] [Accepted: 01/26/2021] [Indexed: 12/17/2022]
Abstract
The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss.
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Affiliation(s)
- Eva Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Berlin Institute of Health, Berlin, Germany
| | - Lukas J Lehner
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Marina Merkel
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Manuel Mayrdorfer
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Wiebke Duettmann
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Marcel G Naik
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Felix Fröhlich
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lutz Liefeldt
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Mareen Pigorsch
- Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Friedersdorff
- Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Danilo Schmidt
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Matthias Niemann
- Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Nils Lachmann
- PIRCHE AG, Berlin, Germany.,HLA Laboratory, Institute for Transfusion Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
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45
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Naylor KL, Knoll GA, McArthur E, Garg AX, Lam NN, Field B, Getchell LE, Hahn E, Kim SJ. Outcomes of an Inpatient Dialysis Start in Patients With Kidney Graft Failure: A Population-Based Multicentre Cohort Study. Can J Kidney Health Dis 2021; 8:2054358120985376. [PMID: 33552528 PMCID: PMC7841655 DOI: 10.1177/2054358120985376] [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: 08/23/2020] [Accepted: 11/28/2020] [Indexed: 11/20/2022] Open
Abstract
Background: The frequency and outcomes of starting maintenance dialysis in the hospital as an inpatient in kidney transplant recipients with graft failure are poorly understood. Objective: To determine the frequency of inpatient dialysis starts in patients with kidney graft failure and examine whether dialysis start status (hospital inpatient vs outpatient setting) is associated with all-cause mortality and kidney re-transplantation. Design: Population-based cohort study. Setting: We used linked administrative healthcare databases from Ontario, Canada. Patients: We included 1164 patients with kidney graft failure from 1994 to 2016. Measurements: All-cause mortality and kidney re-transplantation. Methods: The cumulative incidence function was used to calculate the cumulative incidence of all-cause mortality and kidney re-transplantation, accounting for competing risks. Subdistribution hazard ratios from the Fine and Gray model were used to examine the relationship between inpatient dialysis starts (vs outpatient dialysis start [reference]) and the dependent variables (ie, mortality or re-transplant). Results: We included 1164 patients with kidney graft failure. More than half (55.8%) of patients with kidney graft failure, initiated dialysis as an inpatient. Compared with outpatient dialysis starters, inpatient dialysis starters had a significantly higher cumulative incidence of mortality and a significantly lower incidence of kidney re-transplantation (P < .001). The 10-year cumulative incidence of mortality was 51.9% (95% confidence interval [CI]: 47.4, 56.9%) (inpatient) and 35.3% (95% CI: 31.1, 40.1%) (outpatient). After adjusting for clinical characteristics, we found inpatient dialysis starters had a significantly increased hazard of mortality in the first year after graft failure (hazard ratio: 2.18 [95% CI: 1.43, 3.33]) but at 1+ years there was no significant difference between groups. Limitations: Possibility of residual confounding and unable to determine inpatient dialysis starts that were unavoidable. Conclusions: In this study we identified that most patients with kidney graft failure had inpatient dialysis starts, which was associated with an increased risk of mortality. Further research is needed to better understand the reasons for an inpatient dialysis start in this patient population.
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Affiliation(s)
- Kyla L Naylor
- ICES, ON, Canada.,Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Gregory A Knoll
- Department of Medicine (Nephrology), University of Ottawa and Ottawa Hospital Research Institute, ON, Canada
| | | | - Amit X Garg
- ICES, ON, Canada.,Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.,Division of Nephrology, Western University, London, ON, Canada
| | - Ngan N Lam
- Division of Nephrology, University of Alberta, Edmonton, Canada
| | - Bonnie Field
- Renal Patient and Family Advisory Council, London Health Sciences Centre, ON, Canada
| | - Leah E Getchell
- Division of Nephrology, London Health Sciences Centre, ON, Canada
| | - Emma Hahn
- Division of Nephrology, London Health Sciences Centre, ON, Canada
| | - S Joseph Kim
- Division of Nephrology, Toronto General Hospital, University Health Network and University of Toronto, ON, Canada
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46
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Mayer KA, Doberer K, Eskandary F, Halloran PF, Böhmig GA. New concepts in chronic antibody-mediated kidney allograft rejection: prevention and treatment. Curr Opin Organ Transplant 2021; 26:97-105. [PMID: 33315763 DOI: 10.1097/mot.0000000000000832] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Chronic antibody-mediated rejection (AMR) is a cardinal cause of transplant failure, with currently no proven effective prevention or treatment. The present review will focus on new therapeutic concepts currently under clinical evaluation. RECENT FINDINGS One interesting treatment approach may be interference with interleukin-6 (IL-6) signaling to modulate B-cell immunity and donor-specific antibody (DSA) production. Currently, a large phase III randomized controlled trial is underway to clarify the safety and efficacy of clazakizumab, a high-affinity anti-IL-6 antibody, in chronic AMR. A prevention/treatment strategy may be costimulation blockade using belatacept to interfere with germinal center responses and DSA formation. In a recent uncontrolled study, belatacept conversion was shown to stabilize renal function and dampen AMR activity. Moreover, preliminary clinical results suggest efficacy of CD38 antibodies to deplete plasma and natural killer cells to treat AMR, with anecdotal reports demonstrating at least transient resolution of active rejection. SUMMARY There are promising concepts on the horizon for the prevention and treatment of chronic AMR. The design of adequately powered placebo-controlled trials to clarify the safety and efficacy of such new therapies, however, remains a big challenge, and will rely on the definition of precise surrogate endpoints predicting long-term allograft survival. Mapping the natural history of AMR would greatly help the understanding of who would derive benefits from treatment.
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Affiliation(s)
- Katharina A Mayer
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Konstantin Doberer
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Farsad Eskandary
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Philip F Halloran
- Alberta Transplant Applied Genomics Centre (ATAGC), University of Alberta, Edmonton, AB, Canada
| | - Georg A Böhmig
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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47
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Requião-Moura LR, Albino CRM, Bicalho PR, Ferraz ÉDA, Pires LMDMB, da Silva MFR, Pacheco-Silva A. Long-term outcomes after kidney transplant failure and variables related to risk of death and probability of retransplant: Results from a single-center cohort study in Brazil. PLoS One 2021; 16:e0245628. [PMID: 33471845 PMCID: PMC7816974 DOI: 10.1371/journal.pone.0245628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 01/04/2021] [Indexed: 11/19/2022] Open
Abstract
Background Returning to dialysis after kidney graft loss (GL) is associated with a high risk of mortality, mainly in the first 3–6 months. The follow-up of patients with GL should be extended to better understand crude patient outcomes, mainly in emerging countries, where the transplantation activity has increased. Methods This is a historical single-center cohort study conducted in an emerging country (Brazil) that included 115 transplant patients with kidney allograft failure who were followed for 44.1 (21.4; 72.6) months after GL. The outcomes were death or retransplantation after GL calculated by Kaplan-Meier and log-rank tests. Proportional hazard ratios for death and retransplantation were assessed by Cox regression. Results The 5-year probability of retransplantation was 38.7% (95% CI: 26.1%-51.2%) and that of death was 37.7% (95% CI: 24.9%-50.5%); OR = 1.03 (95% CI: 0.71–1.70) and P = 0.66. The likelihood of retransplantation was higher in patients who resumed dialysis with higher levels of hemoglobin (HR = 1.22; 95% CI = 1.04–1.43; P = 0.01) and lower in blood type O patients (HR = 0.48; 95% CI = 0.25–0.93; P = 0.03), which was associated with a lower frequency of retransplantation with a subsequent living-donor kidney. On the other hand, the risk of death was significantly associated with Charlson comorbidity index (HR for each point = 1.37; 95% CI 1.19–1.50; P<0.001), and residual eGFR at the time when patients had resumed to dialysis (HR for each mL = 1.14; 95% CI = 1.05–1.25; P = 0.002). The trend toward a lower risk of death when patients had resumed to dialysis using AV fistula access was observed (HR = 0.50; 95% CI 0.25–1.02; P = 0.06), while a higher risk seems to be associated with the number of previous engraftment (HR = 2.01; 95% CI 0.99–4.07; P = 0.05). Conclusions The 5-year probability of retransplantation was not less than that of death. Variables related to the probability of retransplantation were hemoglobin level before resuming dialysis and ABO blood type, while the risk of death was associated with comorbidities and residual eGFR.
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Affiliation(s)
- Lúcio R. Requião-Moura
- Renal Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
- * E-mail:
| | | | | | | | | | | | - Alvaro Pacheco-Silva
- Renal Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
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48
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Freist M, Bertrand D, Bailly E, Lambert C, Rouzaire PO, Lemal R, Aniort J, Büchler M, Heng AE, Garrouste C. Management of Immunosuppression After Kidney Transplant Failure: Effect on Patient Sensitization. Transplant Proc 2020; 53:962-969. [PMID: 33288310 DOI: 10.1016/j.transproceed.2020.10.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 10/03/2020] [Accepted: 10/20/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Immunosuppressive treatment is often interrupted in the first months following kidney transplant failure (KTF) to limit side effects. The aim of this study was to assess the effect of prolonged treatment (PT) of more than 3 months' duration after KTF on HLA sensitization and treatment tolerance. METHODS We performed a retrospective observational study involving 119 patients with KTF in 3 French kidney transplant centers between June 2007 and June 2017. Sensitization was defined as the development of HLA donor-specific antibodies (DSA). RESULTS In the PT group receiving calcineurin inhibitor (CNI) treatment, 30 of 52 patients (57.7%) were sensitized vs 52 of 67 patients (77.6%) who had early cessation of treatment (P = .02). The results were confirmed by multivariate analysis (odds ratio [OR] = 0.39, 95% confidence interval [CI] [0.16; 0.98], P = .04). The development of de novo DSAs after CNI treatment (n = 63/90 [70.0%]) was significantly more frequent than during CNI treatment, (n = 18/52 [34.6%], P = .01). Panel-reactive antibody ≥85% was lower in the PT group in multivariate analysis (OR = 0.28, 95% CI [0.10; 0.78], P = .02). No differences in the rates of infection, cardiovascular complications, neoplasia, and deaths were observed between the 2 groups. In multivariate analysis, continuation of corticosteroid treatment had no influence on sensitization but was associated with a higher rate of infection (OR = 2.66, 95% CI [1.09; 6.46], P = .03). CONCLUSION Maintenance of CNI treatment after return to dialysis in patients requesting a repeat transplant could avoid the development of anti-HLA sensitization with a good tolerance.
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Affiliation(s)
- Marine Freist
- Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Dominique Bertrand
- Service de Néphrologie, Centre Hospitalier Régional Universitaire, Rouen, France
| | - Elodie Bailly
- Department of Nephrology and Clinical Immunology, Centre Hospitalier Régional Universitaire de Tours, Tours, France
| | - Céline Lambert
- Biostatistics Unit, University Hospital Clermont-Ferrand, Clermont-Ferrand, France
| | - Paul Olivier Rouzaire
- Department of Human Leucocyte Antigen, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Richard Lemal
- Department of Human Leucocyte Antigen, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Julien Aniort
- Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Matthias Büchler
- Department of Nephrology and Clinical Immunology, Centre Hospitalier Régional Universitaire de Tours, Tours, France
| | - Anne Elisabeth Heng
- Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Cyril Garrouste
- Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
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49
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Plage H, Pielka P, Liefeldt L, Budde K, Ebbing J, Sugünes N, Miller K, Cash H, Bichmann A, Sattler A, Kotsch K, Friedersdorff F. Extended Criteria Donors in Living Kidney Transplantation Including Donor Age, Smoking, Hypertension and BMI. Ther Clin Risk Manag 2020; 16:787-793. [PMID: 32922016 PMCID: PMC7455534 DOI: 10.2147/tcrm.s256962] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 06/14/2020] [Indexed: 12/02/2022] Open
Abstract
Purpose An expansion of selection criteria for deceased organ transplantation already exists to manage the current donor shortage. Comparable evaluation of risk factors for living donors should be investigated to improve this issue. Patients and Methods Our retrospective single-centre study analysed 158 patients with living kidney transplants performed between February 2006 and June 2012. We investigated the influence of donor risk factors (RF) including body mass index over 30 kg/m2, age >60 years, active nicotine abuse and arterial hypertension on postoperative kidney function with focus on the recipients. This was measured for long-term survival and glomerular filtration rate (GFR) in a 5-year follow-up. Results Overall, out of 158 living donors, 84 donors were identified to have no risk factors, whereas 74 donors had at least one risk factor. We noted a significant higher delayed graft function (p=0.042) in the first 7 days after transplantation, as well as lower GFR of recipients of allografts with risk factors in the first-year after transplantation. In our long-term results, there was no significant difference in the functional outcome (graft function, recipient and graft survival) between recipients receiving kidneys from donors with no and at least one risk factors. In the adjusted analysis of subgroups of different risk factors, recipients of donors with “age over 60 years” at time of transplantation had a decreased transplant survival (p=0.014). Conclusion Thus, a careful expansion for selection criteria for living donors with critical evaluation could be possible, but especially the age of the donors could be a limited risk factor.
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Affiliation(s)
- Henning Plage
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Poline Pielka
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Lutz Liefeldt
- Department of Nephrology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Klemens Budde
- Department of Nephrology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Jan Ebbing
- Department of Urology, University Hospital Basel, Urological University Clinic Basel-Liestal, Basel, Switzerland
| | - Nesrin Sugünes
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Kurt Miller
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Hannes Cash
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Anna Bichmann
- Department of Anaesthesia and Operative Intensive Care Medicine, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Arne Sattler
- Department of General, Visceral- and Vascular Surgery, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Katja Kotsch
- Department of General, Visceral- and Vascular Surgery, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Frank Friedersdorff
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
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50
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Bisigniano L, Laham G, Giordani MC, Tagliafichi V, Hansen Krogh D, Maceira A, Rosa-Diez GJ. Reduced survival in patients who return to dialysis after kidney allograft failure. Clin Transplant 2020; 34:e14014. [PMID: 32567723 DOI: 10.1111/ctr.14014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 05/25/2020] [Accepted: 06/04/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND The outcome of patients who return to dialysis after Kidney allograft failure (KAF) remains unclear. Our aim was to compare the outcome of KAF patients vs two different types of transplant naive incident dialysis (TNID) patients, those on the waiting list (WL) and those with a kidney transplant contraindication (KTC). METHODS We performed an observational study using data from the Argentinian Dialysis Registry between 2005 and 2016. We compare mortality between KAF, WL, and KTC. RESULTS We included 75 722 patients of which 2734 were KAF. Survival between the three cohorts (KAF vs WL (n = 14 630) vs KTC (n = 58 358) revealed a significant difference (log-rank test: P < .0001) indicating worse survival for KTC patients and best survival for WL. We found that KAF patients had as poor outcome as KTC patients after multivariate adjustment. Cox regression showed that age >65 years: HR: 1.845 (1.79-1.89) P < .0001, transient catheter: HR: 1.303 (1.26-1.34) P < .0001, diabetic: HR: 1.273 (1.22-1.31) P < .0001, hepatitis C: HR: 1.156 (1.09-1.22) P < .0001, and albumin: HR: 1.247 (1.21-1.28) P < .0001 were associated with mortality. CONCLUSION Patients who return to dialysis after KAF have higher mortality than WL patients and similar to KTC patients.
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Affiliation(s)
- Liliana Bisigniano
- Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Gustavo Laham
- Department of Internal Medicine, Nephrology Section, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Maria Cora Giordani
- Nephrology Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Viviana Tagliafichi
- Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Daniela Hansen Krogh
- Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Alberto Maceira
- Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
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