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Qiu M, Chen S, Chen J, Gao H. Bibliometric study and visual analysis of postoperative diabetes mellitus in kidney transplant recipients based on WoSCC database. Ren Fail 2025; 47:2444383. [PMID: 39806790 PMCID: PMC11734397 DOI: 10.1080/0886022x.2024.2444383] [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: 08/06/2024] [Revised: 11/12/2024] [Accepted: 12/15/2024] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND In recent years, the increase of the post-transplantation diabetes mellitus (PTDM) after renal transplantation encourages people to do a lot of research on the disease. This paper conducted a bibliometric study on PTDM related literature to explore the risk factors of diabetes after kidney transplantation, as well as the current status, hotspots and development trends of PTDM research, so as to provide reference for researchers in related fields. METHODS We searched the Web of Science Core Collection (WoSCC) database for PTDM literature from January 1, 1990, to August 20, 2023, and used VOSviewer, CiteSpace, and the R package 'bibliometrix' to do bibliometric analysis. RESULTS Obesity, 3 months after transplantation tacrolimus concentration >10 ng/mL, temporary hyperglycemia, delayed graft function, acute rejection is specific risk factors related to PTDM in renal transplant recipients. In addition, 74 countries led by China and the United States published 1546 papers, and the number of PTDM-related publications is increasing every year. Primary institutions included the University of California, Los Angeles, Mayo Clinic, University of Oslo, and University of Toronto. The Journal of Transplantation is the most widely read journal in the subject. The authors with the most published literature are Trond Jenssen and Adnan Sharif, and the most cited author is Kasiske BL. Expectations for continued growth in global PTDM research are increasingly high. Future studies will mainly focus on exploring the risk factors of PTDM and identifying new therapeutic approaches and targets.
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Affiliation(s)
- Minhua Qiu
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Clinical Research Center for Kidney Diseases of Integrated Traditional Chinese and Western Medicine, Nanning, China
| | - Sheng Chen
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Clinical Research Center for Kidney Diseases of Integrated Traditional Chinese and Western Medicine, Nanning, China
| | - Jibing Chen
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Clinical Research Center for Kidney Diseases of Integrated Traditional Chinese and Western Medicine, Nanning, China
| | - Hongjun Gao
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Clinical Research Center for Kidney Diseases of Integrated Traditional Chinese and Western Medicine, Nanning, China
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Popović L, Bulum T. New Onset Diabetes After Organ Transplantation: Risk Factors, Treatment, and Consequences. Diagnostics (Basel) 2025; 15:284. [PMID: 39941214 PMCID: PMC11816453 DOI: 10.3390/diagnostics15030284] [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: 12/09/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
New onset diabetes mellitus after organ transplantation (NODAT) is a frequent and serious complication of solid organ transplantation. It significantly impacts graft function, patient survival, and quality of life. NODAT is diagnosed based on the criteria for type 2 diabetes, with the oral glucose tolerance test (OGTT) serving as the gold standard for diagnosis. The development of NODAT is influenced by a range of risk factors, which are classified into modifiable and non-modifiable categories. Post-transplant, regular glycemic monitoring at specific intervals is essential for timely diagnosis and initiation of therapy. Early intervention can help prevent or delay the onset of diabetes-related complications. The treatment strategy for NODAT involves lifestyle modifications and pharmacological interventions. These include medications such as metformin, sulfonylureas, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and insulin. Adjusting immunosuppressive therapy-either by reducing dosages or substituting drugs with lower diabetogenic potential-is a common preventative and therapeutic measure. However, this must be performed cautiously to avoid acute graft rejection, which poses a greater risk to the patient compared to NODAT itself. In addition to managing diabetes, addressing comorbidities such as hypertension and dyslipidemia is crucial, as they elevate the risk of cardiovascular events and mortality. Patients with NODAT are also prone to developing common diabetes-related complications, including diabetic nephropathy, neuropathy, retinopathy, and peripheral vascular disease. Therefore, regular follow-ups and appropriate treatment are vital to maintaining quality of life and improving long-term outcomes.
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Affiliation(s)
- Lucija Popović
- Department of Emergency Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - Tomislav Bulum
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Department of Diabetes and Endocrinology, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Dugi dol 4a, 10000 Zagreb, Croatia
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Le Ha K, Nguyen Van D, Do Manh H, Tran Thi D, Nguyen Trung K, Le Viet T, Nguyen Thi Thu H. Elevated Plasma High Sensitive C-Reactive Protein and Triglyceride/High-Density Lipoprotein Cholesterol Ratio are Risks Factors of Diabetes Progression in Prediabetes Patients After Kidney Transplant: A 3-Year Single-Center Study in Vietnam. Int J Gen Med 2024; 17:5095-5103. [PMID: 39526064 PMCID: PMC11550698 DOI: 10.2147/ijgm.s490561] [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: 08/07/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose Determination the rate of developing post-transplant diabetes mellitus (PTDM) in prediabetic patients and the relationship with plasma hs-CRP levels and TG/HDL-C ratio in patients after kidney transplantation from living donors followed for 3 years. Subjects and Methods A total of 206 post-transplant patients diagnosed with prediabetes by oral glucose tolerance test (OGTT) were included in the study. At the time of diagnosis of prediabetes, all patients were clinically examined, paraclinical tests were performed, plasma hs-CRP was quantified, and the TG/HDL-C ratio was determined. Patients are individualized and given a reasonable diet and exercise regimen. Patients had their fasting blood glucose measured monthly or had an OGTT every 3 months. Patients meeting the criteria for diagnosis of PTDM according to the American Diabetes Association (ADA)-2018 were collected during 3 years of follow-up. Results The study group had an average age of 39.46 ± 10.26 years old, including 74.8% males and 25.2% females. The rate of patients who had a development of PTDM from prediabetes was 29.6% (61/206 patients). BMI, plasma TG, HDL-C, hs-CRP, and TG/HDL-C ratio at the time of prediabetes diagnosis were factors related to the progression of PTDM, in which hs-CRP and TG/HDL-C ratio were good predictors (with AUC = 0.85 and 0.874, respectively; p < 0.001). Conclusion After 3 years of follow-up, nearly one-third of prediabetic patients developed PTDM post-living donor kidney transplantation. BMI, plasma TG, HDL-C, hs-CRP, and the TG/HDL-C ratio were linked to DM progression, with hs-CRP and TG/HDL-C being the strongest predictors.
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Affiliation(s)
- Khoa Le Ha
- Hanoi Medical University, Hanoi, Vietnam
| | - Duc Nguyen Van
- Organ Transplant Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Ha Do Manh
- Organ Transplant Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Doan Tran Thi
- Department of Metabolic Disorders and Cardiology, National Hospital of Endocrinology, Hanoi, Vietnam
| | - Kien Nguyen Trung
- Hematology and Blood Transfusion Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Thang Le Viet
- Organ Transplant Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Ha Nguyen Thi Thu
- Organ Transplant Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
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Rudzki G, Knop-Chodyła K, Piasecka Z, Kochanowska-Mazurek A, Głaz A, Wesołek-Bielaska E, Woźniak M. Managing Post-Transplant Diabetes Mellitus after Kidney Transplantation: Challenges and Advances in Treatment. Pharmaceuticals (Basel) 2024; 17:987. [PMID: 39204092 PMCID: PMC11357592 DOI: 10.3390/ph17080987] [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: 06/25/2024] [Revised: 07/10/2024] [Accepted: 07/16/2024] [Indexed: 09/03/2024] Open
Abstract
Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.
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Affiliation(s)
- Grzegorz Rudzki
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Kinga Knop-Chodyła
- University Clinical Hospital No. 4 in Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (K.K.-C.); (E.W.-B.)
| | - Zuzanna Piasecka
- Saint Queen Jadwiga’s Regional Clinical Hospital No. 2 in Rzeszow, Lwowska 60, 35-301 Rzeszów, Poland;
| | - Anna Kochanowska-Mazurek
- Stefan Cardinal Wyszynski Province Specialist Hospital, al. Kraśnicka 100, 20-718 Lublin, Poland;
| | - Aneta Głaz
- Faculty of medicine, Medical University of Lublin, al. Racławickie 1, 20-059 Lublin, Poland;
| | - Ewelina Wesołek-Bielaska
- University Clinical Hospital No. 4 in Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (K.K.-C.); (E.W.-B.)
| | - Magdalena Woźniak
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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Du Q, Li T, Yi X, Song S, Kang J, Jiang Y. Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis. Acta Diabetol 2024; 61:809-829. [PMID: 38507083 DOI: 10.1007/s00592-024-02253-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/01/2024] [Indexed: 03/22/2024]
Abstract
AIMS Post-transplant diabetes is a prevalent and consequential complication following kidney transplantation, which significantly augments the risk of cardiovascular disease, graft loss, infection, and mortality, thereby profoundly impacting both graft and patient survival. However, the early stages of post-transplant diabetes often go unnoticed or receive inadequate management. Consequently, this study systematically assesses the incidence of new-onset diabetes after kidney transplantation with the aim to enhance medical staff awareness regarding post-transplantation diabetes and provide clinical management guidance. METHODS We conducted a comprehensive search across multiple databases including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed until September 21, 2023. Data extraction was performed using standardized tables and meta-analysis was conducted using Stata 16.0 software. A random effects model was employed to estimate the combined prevalence along with its corresponding 95% confidence interval. The source of heterogeneity was explored using subgroup analysis and sensitivity analysis, while publication bias was assessed through funnel plot and Egger's test. This study has been registered with PROSPERO under the registration number CRD42023465768. RESULTS This meta-analysis comprised 39 studies with a total sample size of 16,584 patients. The prevalence of new-onset diabetes after transplantation was found to be 20% [95% CI (18.0, 22.0)]. Subgroup analyses were conducted based on age, gender, body mass index, family history of diabetes, type of kidney donor, immunosuppressive regimen, acute rejection episodes, hepatitis C infection status and cytomegalovirus infection. CONCLUSIONS The incidence of post-kidney transplantation diabetes is substantial, necessitating early implementation of preventive and control measures to mitigate its occurrence, enhance prognosis, and optimize patients' quality of life. CLINICAL TRIAL REGISTRATION PROSPERO: CRD42023465768.
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Affiliation(s)
- Qiufeng Du
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Tao Li
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Xiaodong Yi
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Shuang Song
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Jing Kang
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Yunlan Jiang
- Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu City, 610072, Sichuan Province, China.
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Alajous S, Budhiraja P. New-Onset Diabetes Mellitus after Kidney Transplantation. J Clin Med 2024; 13:1928. [PMID: 38610694 PMCID: PMC11012473 DOI: 10.3390/jcm13071928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/19/2024] [Accepted: 03/24/2024] [Indexed: 04/14/2024] Open
Abstract
New-Onset Diabetes Mellitus after Transplantation (NODAT) emerges as a prevalent complication post-kidney transplantation, with its incidence influenced by variations in NODAT definitions and follow-up periods. The condition's pathophysiology is marked by impaired insulin sensitivity and β-cell dysfunction. Significant risk factors encompass age, gender, obesity, and genetics, among others, with the use of post-transplant immunosuppressants intensifying the condition. NODAT's significant impact on patient survival and graft durability underscores the need for its prevention, early detection, and treatment. This review addresses the complexities of managing NODAT, including the challenges posed by various immunosuppressive regimens crucial for transplant success yet harmful to glucose metabolism. It discusses management strategies involving adjustments in immunosuppressive protocols, lifestyle modifications, and pharmacological interventions to minimize diabetes risk while maintaining transplant longevity. The importance of early detection and proactive, personalized intervention strategies to modify NODAT's trajectory is also emphasized, advocating for a shift towards more anticipatory post-transplant care.
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Affiliation(s)
| | - Pooja Budhiraja
- Division of Medicine, Mayo Clinic Arizona, Phoenix, AZ 85054, USA;
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Liu Y, Xu H, Yan N, Tang Z, Wang Q. Research progress of ophthalmic preparations of immunosuppressants. Drug Deliv 2023; 30:2175925. [PMID: 36762580 DOI: 10.1080/10717544.2023.2175925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023] Open
Abstract
Immune ophthalmopathy is a collection of autoimmune eye diseases. Immunosuppressants are drugs that can inhibit the body's immune response. Considering drug side effects such as hepatorenal toxicity and the unique structure of the eye, incorporating immunosuppressants into ophthalmic nanodrug delivery systems, such as microparticles, nanoparticles, liposomes, micelles, implants, and in situ gels, has the advantages of improving solubility, increasing bioavailability, high eye-target specificity, and reducing side effects. This study reviews recent research and applications of this aspect to provide a reference for the development of an ophthalmic drug delivery system.
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Affiliation(s)
- Ye Liu
- School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China
| | - Haonan Xu
- School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China
| | - Na Yan
- Department of Pharmacy, Jin Hua Municipal Maternal and Child Health Care Hospital, Jinhua, Zhejiang, 321000, China
| | - Zhan Tang
- School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China.,Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China
| | - Qiao Wang
- School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China.,Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China
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Luu D, Shah T, Sakharkar P, Min DI. Genetic variations in a Sestrin2/Sestrin3/mTOR Axis and development of new-onset diabetes after kidney transplantation. Transpl Immunol 2023; 81:101947. [PMID: 37918578 DOI: 10.1016/j.trim.2023.101947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/24/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Genetic variations in Sestrin2/Sestrin3/ mTOR axis may cause obesity-associated metabolic syndrome, including lipid accumulation and insulin resistance thereby increasing individual's risk of diabetes. In this study, we explored the association between single nucleotide polymorphisms (SNPs) of these genes and new onset diabetes after transplantation in Hispanic renal transplant recipients (RTRs). METHODS Nine potential functional polymorphisms in Sestrin2, Sestrin3 and mTOR genes were genotyped using the Taqman qPCR method in this study. We compared 160 Hispanic RTRs with no evidence of pre-existing diabetes, who developed new onset diabetes after transplantation (NODAT) with 152 controls with no history of diabetes. The logistic proportional hazard model was used to examine risks for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. RESULTS Significant associations were observed between NODAT and mTOR TT (rs2295080 OR = 1.79, 95% CI =1.14-2.82, p = 0.01), Sestrin2 AA (rs580800, OR = 0.42, 95% CI =0.27-0.67, p = 0.002), and Sestrin3 AA (rs684856, OR = 0.45, 95% CI = 0.27-0.75, p = 0.001). Sestrin2 AA (rs580800), Sestrin3 AA (rs684856) and mTOR TT (rs2295080) remained significantly associated with NODAT after adjusting for acute rejection and sirolimus use. No interactions observed between the mTOR rs2295080 and Sestrin3 rs684856 and risk of NODAT (mTOR rs2295080 and Sestrin3 rs684856, p = 0.123 and mTOR rs2295080 and Sestrin2 rs580800, p = 0.167). Of the nongenetic factors, use of sirolimus and older age were associated with an increased risk for NODAT. CONCLUSION Polymorphisms in the Sestrin2/Sestrin3/ mTOR gene may confer certain protection/predisposition for NODAT.
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Affiliation(s)
- Don Luu
- Saint Vincent Medical Center, Los Angeles, CA, United States of America; Transplant Research Institute, Los Angeles, CA, United States of America; Western University of Health Sciences, Pomona, CA, United States of America.
| | - Tariq Shah
- Saint Vincent Medical Center, Los Angeles, CA, United States of America; Transplant Research Institute, Los Angeles, CA, United States of America
| | - Prashant Sakharkar
- Roosevelt University College of Pharmacy, Schaumburg, IL, United States of America
| | - David I Min
- Saint Vincent Medical Center, Los Angeles, CA, United States of America; Western University of Health Sciences, Pomona, CA, United States of America
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Gupta SK, Mostofsky E, Motiwala SR, Hage A, Mittleman MA. Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study. Front Endocrinol (Lausanne) 2023; 14:1248940. [PMID: 37929038 PMCID: PMC10623448 DOI: 10.3389/fendo.2023.1248940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/02/2023] [Indexed: 11/07/2023] Open
Abstract
Introduction Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. Methods We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. Results In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. Conclusion The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.
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Affiliation(s)
- Suruchi K. Gupta
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
- Harvard Medical School, Boston, MA, United States
| | - Elizabeth Mostofsky
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Shweta R. Motiwala
- Harvard Medical School, Boston, MA, United States
- Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Ali Hage
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- London Health Sciences Centre, Schulich School of Medicine, Western University, London, ON, Canada
| | - Murray A. Mittleman
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Harvard Medical School, Boston, MA, United States
- Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
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Soliman M, Eskander A, Effat H, Fayad T, Elgohary T. Adverse Cardiovascular Events in Post-Renal Transplant Patients, a Retrospective Study of Five Hundred Cases Over Twenty-Two Years. CURRENT TRANSPLANTATION REPORTS 2023; 10:89-99. [DOI: 10.1007/s40472-023-00399-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 10/13/2023]
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Klupa T, Czupryniak L, Dzida G, Fichna P, Jarosz-Chobot P, Gumprecht J, Mysliwiec M, Szadkowska A, Bomba-Opon D, Czajkowski K, Malecki MT, Zozulinska-Ziolkiewicz DA. Expanding the Role of Continuous Glucose Monitoring in Modern Diabetes Care Beyond Type 1 Disease. Diabetes Ther 2023:10.1007/s13300-023-01431-3. [PMID: 37322319 PMCID: PMC10299981 DOI: 10.1007/s13300-023-01431-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 05/31/2023] [Indexed: 06/17/2023] Open
Abstract
Application of continuous glucose monitoring (CGM) has moved diabetes care from a reactive to a proactive process, in which a person with diabetes can prevent episodes of hypoglycemia or hyperglycemia, rather than taking action only once low and high glucose are detected. Consequently, CGM devices are now seen as the standard of care for people with type 1 diabetes mellitus (T1DM). Evidence now supports the use of CGM in people with type 2 diabetes mellitus (T2DM) on any treatment regimen, not just for those on insulin therapy. Expanding the application of CGM to include all people with T1DM or T2DM can support effective intensification of therapies to reduce glucose exposure and lower the risk of complications and hospital admissions, which are associated with high healthcare costs. All of this can be achieved while minimizing the risk of hypoglycemia and improving quality of life for people with diabetes. Wider application of CGM can also bring considerable benefits for women with diabetes during pregnancy and their children, as well as providing support for acute care of hospital inpatients who experience the adverse effects of hyperglycemia following admission and surgical procedures, as a consequence of treatment-related insulin resistance or reduced insulin secretion. By tailoring the application of CGM for daily or intermittent use, depending on the patient profile and their needs, one can ensure the cost-effectiveness of CGM in each setting. In this article we discuss the evidence-based benefits of expanding the use of CGM technology to include all people with diabetes, along with a diverse population of people with non-diabetic glycemic dysregulation.
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Affiliation(s)
- Tomasz Klupa
- Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
| | - Leszek Czupryniak
- Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Grzegorz Dzida
- Department of Internal Diseases, Medical University of Lublin, Lublin, Poland
| | - Piotr Fichna
- Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Katowice, Poland
| | - Malgorzata Mysliwiec
- Department of Pediatrics, Diabetology and Endocrinology, Medical University of Gdansk, Gdansk, Poland
| | - Agnieszka Szadkowska
- Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland
| | - Dorota Bomba-Opon
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Czajkowski
- 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Maciej T Malecki
- Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland
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Wolde HF, Molla MD, Aragie H, Adugna DG, Teferi ET, Melese EB, Assefa YA, Kifle H, Worku YB, Belay DG, Kibret AA. High burden of diabetes and prediabetes among cancer patients at University of Gondar comprehensive specialized hospital, Northwest Ethiopia. Sci Rep 2023; 13:9431. [PMID: 37296304 PMCID: PMC10256839 DOI: 10.1038/s41598-023-36472-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 06/04/2023] [Indexed: 06/12/2023] Open
Abstract
Cancer and diabetes mellitus (DM) are diagnosed within the same individual more frequently and share common risk factors. Although diabetes among cancer patients may result in more aggressive clinical courses of cancer, there is limited evidence about its burden and associated factors. Hence, this study aimed to assess the burden of diabetes and prediabetes among cancer patients and its associated factors. Institution-based cross-sectional study was conducted at the University of Gondar comprehensive specialized hospital from 10 January to 10 March 2021. A systematic random sampling technique was used to select 423 cancer patients. The data was collected using a structured interviewer-administered questionnaire. Prediabetes and diabetes diagnosis was made based on World Health Organization (WHO) criteria. Bi-variable and multivariable binary logistic regression models were fitted to identify factors associated with the outcome. Adjusted Odds Ratio (AOR) with a 95% confidence interval was estimated to show the direction and strength of associations. Variables with a p-value less than 0.05 in the multivariable model were considered significantly associated with the outcome. The final analysis was based on 384 patients with cancer. The proportion of prediabetes and diabetes was 56.8% (95% CI 51.7, 61.7) and 16.7% (95% CI 13.3, 20.8), respectively. Alcohol consumption was found to increase the odds of elevated blood sugar among cancer patients (AOR: 1.96; 95%CI: 1.11, 3.46). The burden of prediabetes and diabetes is alarmingly high among cancer patients. Besides, alcohol consumption was found to increase the odds of having elevated blood sugar among cancer patients. Hence, it is essential to recognize cancer patients are at high risk of having elevated blood sugar and design strategies to integrate diabetes and cancer care.
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Affiliation(s)
- Haileab Fekadu Wolde
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Meseret Derbew Molla
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Hailu Aragie
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Dagnew Getnet Adugna
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Ephrem Tafesse Teferi
- Department of Internal Medicine School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Endalkachew Belayneh Melese
- Department of Internal Medicine School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Yohannes Awoke Assefa
- Department of Occupational Therapy School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Habtu Kifle
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Yilkal Belete Worku
- Department of Internal Medicine School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Daniel Gashaneh Belay
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Anteneh Ayelign Kibret
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
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13
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Granata S, Mercuri S, Troise D, Gesualdo L, Stallone G, Zaza G. mTOR-inhibitors and post-transplant diabetes mellitus: a link still debated in kidney transplantation. Front Med (Lausanne) 2023; 10:1168967. [PMID: 37250653 PMCID: PMC10213242 DOI: 10.3389/fmed.2023.1168967] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 04/25/2023] [Indexed: 05/31/2023] Open
Abstract
The mammalian target of rapamycin inhibitors (mTOR-Is, Sirolimus, and Everolimus) are immunosuppressive drugs widely employed in kidney transplantation. Their main mechanism of action includes the inhibition of a serine/threonine kinase with a pivotal role in cellular metabolism and in various eukaryotic biological functions (including proteins and lipids synthesis, autophagy, cell survival, cytoskeleton organization, lipogenesis, and gluconeogenesis). Moreover, as well described, the inhibition of the mTOR pathway may also contribute to the development of the post-transplant diabetes mellitus (PTDM), a major clinical complication that may dramatically impact allograft survival (by accelerating the development of the chronic allograft damage) and increase the risk of severe systemic comorbidities. Several factors may contribute to this condition, but the reduction of the beta-cell mass, the impairment of the insulin secretion and resistance, and the induction of glucose intolerance may play a pivotal role. However, although the results of several in vitro and in animal models, the real impact of mTOR-Is on PTDM is still debated and the entire biological machinery is poorly recognized. Therefore, to better elucidate the impact of the mTOR-Is on the risk of PTDM in kidney transplant recipients and to potentially uncover future research topics (particularly for the clinical translational research), we decided to review the available literature evidence regarding this important clinical association. In our opinion, based on the published reports, we cannot draw any conclusion and PTDM remains a challenge. However, also in this case, the administration of the lowest possible dose of mTOR-I should also be recommended.
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Affiliation(s)
- Simona Granata
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Silvia Mercuri
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Dario Troise
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Loreto Gesualdo
- Renal, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari, Bari, Italy
| | - Giovanni Stallone
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gianluigi Zaza
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
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14
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Zhang Z, Sun J, Guo M, Yuan X. Progress of new-onset diabetes after liver and kidney transplantation. Front Endocrinol (Lausanne) 2023; 14:1091843. [PMID: 36843576 PMCID: PMC9944581 DOI: 10.3389/fendo.2023.1091843] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/27/2023] [Indexed: 02/11/2023] Open
Abstract
Organ transplantation is currently the most effective treatment for end-stage organ failure. Post transplantation diabetes mellitus (PTDM) is a severe complication after organ transplantation that seriously affects the short-term and long-term survival of recipients. However, PTDM is often overlooked or poorly managed in its early stage. This article provides an overview of the incidence, and pathogenesis of and risk factors for PTDM, aiming to gain a deeper understanding of PTDM and improve the quality of life of recipients.
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Affiliation(s)
- Zhen Zhang
- Department of Urology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Jianyun Sun
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Meng Guo
- National Key Laboratory of Medical Immunology &Institute of Immunology, Navy Medical University, Shanghai, China
| | - Xuemin Yuan
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
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15
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Jose N, Varughese S. Not so sweet!!: Posttransplant diabetes ‒ An update for the nephrologist. INDIAN JOURNAL OF TRANSPLANTATION 2023. [DOI: 10.4103/ijot.ijot_97_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
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16
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Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Harreiter J, Kautzky‐Willer A, Leutner M, Werzowa J, Tura A, Budde K, Eller K, Pascual J, Krebs M, Jenssen TG, Hecking M. Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial. Am J Transplant 2022; 22:2880-2891. [PMID: 36047565 PMCID: PMC10087499 DOI: 10.1111/ajt.17187] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 08/09/2022] [Accepted: 08/29/2022] [Indexed: 01/25/2023]
Abstract
Posttransplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA1c as alternatives to oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2hPG) using sensitivity and specificity in 263 kidney transplant recipients (KTRs) from a clinical trial. Between visits at 6, 12, and 24 months after transplantation, 28%-31% of patients switched glycemic category (normal glucose tolerance [NGT], IGT/IFG, PTDM). Correlations of FPG and HbA1c against 2hPG were lower at 6 months (r = 0.59 [FPG against 2hPG]; r = 0.45 [HbA1c against 2hPG]) vs. 24 months (r = 0.73 [FPG against 2hPG]; r = 0.74 [HbA1c against 2hPG]). Up to 69% of 2hPG-defined PTDM cases were missed by conventional HbA1c and FPG thresholds. For prediabetes, concordance of FPG and HbA1c with 2hPG ranged from 6%-9%. In conclusion, in our well-defined randomized trial cohort, one-third of KTRs switched glycemic category over 2 years and although the correlations of FPG and HbA1c with 2hPG improved with time, their diagnostic concordance was poor for PTDM and, especially, prediabetes. Considering posttransplant metabolic instability, FPG's and HbA1c 's diagnostic performance, the OGTT remains indispensable to diagnose PTDM and prediabetes after kidney transplantation.
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Affiliation(s)
- Amelie Kurnikowski
- Internal Medicine III, Nephrology and DialysisMedical University of ViennaViennaAustria
| | - Espen Nordheim
- Department of Transplantation Medicine, NephrologyOslo University Hospital, RikshospitaletOsloNorway
- Faculty of Clinical MedicineUniversity of OsloOsloNorway
| | - Elisabeth Schwaiger
- Internal Medicine III, Nephrology and DialysisMedical University of ViennaViennaAustria
- Department of Internal Medicine I, Cardiology and Nephrology, Krankenhaus der Barmherzigen Brüder EisenstadtEisenstadtAustria
| | - Simon Krenn
- Internal Medicine III, Nephrology and DialysisMedical University of ViennaViennaAustria
| | - Jürgen Harreiter
- Internal Medicine III, Endocrinology and MetabolismMedical University of ViennaViennaAustria
| | | | - Michael Leutner
- Internal Medicine III, Endocrinology and MetabolismMedical University of ViennaViennaAustria
| | - Johannes Werzowa
- Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre MeidlingViennaAustria
- 1st Medical Department, Hanusch HospitalViennaAustria
| | | | - Klemens Budde
- Medizinische Klinik m. S. NephrologieCharité Universitätsmedizin BerlinBerlinGermany
| | - Kathrin Eller
- Clinical Division of Nephrology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Julio Pascual
- Department of NephrologyHospital del Mar‐Institut Hospital del Mar d'Investigacions Mèdiques (IMIM)BarcelonaSpain
| | - Michael Krebs
- Internal Medicine III, Endocrinology and MetabolismMedical University of ViennaViennaAustria
| | - Trond Geir Jenssen
- Department of Transplantation Medicine, NephrologyOslo University Hospital, RikshospitaletOsloNorway
- Faculty of Clinical MedicineUniversity of OsloOsloNorway
- Metabolic and Renal Research Group, Faculty of Health SciencesUiT‐ The Arctic University of NorwayTromsøNorway
| | - Manfred Hecking
- Internal Medicine III, Nephrology and DialysisMedical University of ViennaViennaAustria
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17
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Xie D, Guo J, Dang R, Li Y, Si Q, Han W, Wang S, Wei N, Meng J, Wu L. The effect of tacrolimus-induced toxicity on metabolic profiling in target tissues of mice. BMC Pharmacol Toxicol 2022; 23:87. [PMID: 36443830 PMCID: PMC9703746 DOI: 10.1186/s40360-022-00626-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 11/14/2022] [Indexed: 11/29/2022] Open
Abstract
Tacrolimus (Tac) is a common immunosuppressant that used in organ transplantation. However, its therapeutic index is narrow, and it is prone to adverse side effects, along with an increased risk of toxicity, namely, cardio-, nephro-, hepato-, and neurotoxicity. Prior metabolomic investigations involving Tac-driven toxicity primarily focused on changes in individual organs. However, extensive research on multiple matrices is uncommon. Hence, in this research, the authors systemically evaluated Tac-mediated toxicity in major organs, namely, serum, brain, heart, liver, lung, kidney, and intestines, using gas chromatography-mass spectrometry (GC-MS). The authors also employed multivariate analyses, including orthogonal projections to the latent structure (OPLS) and t-test, to screen 8 serum metabolites, namely, D-proline, glycerol, D-fructose, D-glucitol, sulfurous acid, 1-monopalmitin (MG (16:0/0:0/0:0)), glycerol monostearate (MG (0:0/18:0/0:0)), and cholesterol. Metabolic changes within the brain involved alterations in the levels of butanamide, tartronic acid, aminomalonic acid, scyllo-inositol, dihydromorphine, myo-inositol, and 11-octadecenoic acid. Within the heart, the acetone and D-fructose metabolites were altered. In the liver, D-glucitol, L-sorbose, palmitic acid, myo-inositol, and uridine were altered. In the lung, L-lactic acid, L-5-oxoproline, L-threonine, phosphoric acid, phosphorylethanolamine, D-allose, and cholesterol were altered. Lastly, in the kidney, L-valine and D-glucose were altered. Our findings will provide a systematic evaluation of the metabolic alterations in target organs within a Tac-driven toxicity mouse model.
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Affiliation(s)
- Dadi Xie
- grid.508306.8Tengzhou Central People’s Hospital, Tengzhou, 277500 China
| | - Jinxiu Guo
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Ruili Dang
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Yanan Li
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Qingying Si
- grid.508306.8Tengzhou Central People’s Hospital, Tengzhou, 277500 China
| | - Wenxiu Han
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Shan Wang
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Ning Wei
- Department of Gastroenterology, Shanting District People’s Hospital, Zaozhuang, 277200 China
| | - Junjun Meng
- grid.459518.40000 0004 1758 3257Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, 272000 China
| | - Linlin Wu
- grid.508306.8Tengzhou Central People’s Hospital, Tengzhou, 277500 China
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18
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Incidence, Risk Factors and Clinical Implications of Glucose Metabolic Changes after Heart Transplant. Biomedicines 2022; 10:biomedicines10112704. [DOI: 10.3390/biomedicines10112704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/17/2022] [Accepted: 10/24/2022] [Indexed: 11/17/2022] Open
Abstract
Diabetes mellitus (DM) arising de novo after transplant is a common complication, sharing many features with type 2 DM but also specific causes, such as administration of steroids and immunosuppressive drugs. Although post-transplant DM (PTDM) is generally assumed to worsen recipients’ outcomes, its impact on renal function, cardiac allograft vasculopathy and mortality remains understudied in heart transplant (HT). We evaluated incidence and risk factors of PTDM and studied glucose metabolic alterations in relation to major HT outcomes. 119 subjects were included in this retrospective, single centre, observational study. A comprehensive assessment of glucose metabolic state was done pre-transplant and a median of 60 months [IQR 30–72] after transplant. Most patients were males (75.6%), with prior non-ischemic cardiomyopathy (64.7%) and median age of 58 years [IQR 48–63]. 14 patients developed PTDM, an incidence of 3.2 cases/100 patient-years. Patients with worsening glucose metabolic pattern were the only who showed a significant increase of BMI and metabolic syndrome prevalence after transplant. 23 (19.3%) patients died during follow up. Early mortality was lower in those with stably normal glucose metabolism, whereas improvement of glucose metabolic state favorably affected mid-term mortality (log-rank p = 0.028). No differences were observed regarding risk of infections and cancer. PTDM is common, but glucose metabolism may also improve after HT. PTDM is strictly related with BMI increase and metabolic syndrome development and may impact recipient survival.
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19
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Newman JD, Schlendorf KH, Cox ZL, Zalawadiya SK, Powers AC, Niswender KD, Shah RV, Lindenfeld J. Post-transplant diabetes mellitus following heart transplantation. J Heart Lung Transplant 2022; 41:1537-1546. [DOI: 10.1016/j.healun.2022.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/22/2022] [Accepted: 07/13/2022] [Indexed: 10/31/2022] Open
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20
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Dos Santos Q, Hornum M, Terrones-Campos C, Crone CG, Wareham NE, Soeborg A, Rasmussen A, Gustafsson F, Perch M, Soerensen SS, Lundgren J, Feldt-Rasmussen B, Reekie J. Posttransplantation Diabetes Mellitus Among Solid Organ Recipients in a Danish Cohort. Transpl Int 2022; 35:10352. [PMID: 35449717 PMCID: PMC9016119 DOI: 10.3389/ti.2022.10352] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/15/2022] [Indexed: 12/15/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0–45 days; 46–365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46–365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16–2.69 and aHR: 1.89, 95% CI: 1.17–3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients.
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Affiliation(s)
- Quenia Dos Santos
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Mads Hornum
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Cynthia Terrones-Campos
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Cornelia Geisler Crone
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Neval Ete Wareham
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Soeborg
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark
| | - Finn Gustafsson
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | - Michael Perch
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | | | - Jens Lundgren
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Joanne Reekie
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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21
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Chaitou AR, Valmiki S, Valmiki M, Zahid M, Aid MA, Fawzy P, Khan S. New-Onset Diabetes Mellitus (NODM) After Liver Transplantation (LT): The Ultimate Non-diabetogenic Immunosuppressive Therapy. Cureus 2022; 14:e23635. [PMID: 35510006 PMCID: PMC9057316 DOI: 10.7759/cureus.23635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 03/29/2022] [Indexed: 11/05/2022] Open
Abstract
New-onset diabetes mellitus (NODM) is a common long-term complication after liver transplantation (LT). It is thought to be drug-induced in most cases, no matter the underlying disease that cause liver failure and indicated transplantation. Standard post-transplantation (PT) immunosuppressive regimens include prolonged use of calcineurin inhibitors (CNIs), namely tacrolimus (TAC), alongside corticosteroids to avoid acute and chronic graft rejection. This combination is well known for its diabetogenicity. Significant differences between the applied regimens stand out concerning the duration and dosages to prevent the metabolic side effects of these drugs in the long run without compromising the graft's survival. Studies were collected after an extensive research of PubMed database for this very specific topic using the following MeSH keywords in multiple combinations: "Liver Transplantation," "Diabetes Mellitus," "NODM," "Tacrolimus," "Cyclosporine A," and "Steroids." In addition, we used the same keywords for regular searches in Google Scholar. Only the relevant English human studies between 2010 and 2020 were collected except for review articles. Duplicates were eliminated using Mendeley software. Twelve relevant studies directly related to the targeted topic were collected and discussed, including five retrospective cohorts, four prospective cohorts, one clinical trial, one prospective pilot, and one case report. Their topics included primarily the factors increasing the risk of new-onset diabetes mellitus after liver transplantation (NODALT), TAC-based immunosuppression and its relative blood levels affecting the possible development of NODALT, the role of cyclosporine in substituting TAC regimen, and the effect of different steroids-avoiding protocols on the prevention of NODALT. The reviewed studies suggested that lowering the serum concentration of tacrolimus (cTAC) throughout the PT period and eliminating the corticosteroids regimen as early as possible, among other measures, can significantly impact the rate of emergence of NODM. This traditional review tackles the most recent studies about NODALT to establish a comprehensive view on this issue and guide clinicians and researchers for the safest immunosuppressive regimen to date, while maintaining a balanced metabolic profile.
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22
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Rozenberg D, Santa Mina D, Nourouzpour S, Camacho Perez E, Stewart BL, Wickerson L, Tsien C, Selzner N, Shore J, Aversa M, Woo M, Holdsworth S, Prevost K, Park J, Azhie A, Huszti E, McLeod E, Dales S, Bhat M. Feasibility of a Home-Based Exercise Program for Managing Posttransplant Metabolic Syndrome in Lung and Liver Transplant Recipients: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc 2022; 11:e35700. [PMID: 35319467 PMCID: PMC8987959 DOI: 10.2196/35700] [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: 12/16/2021] [Accepted: 12/21/2021] [Indexed: 12/05/2022] Open
Abstract
Background Posttransplant metabolic syndrome (PTMS) is a common contributor to morbidity and mortality among solid organ transplant recipients in the late posttransplant period (≥1 year). Patients diagnosed with PTMS are at a higher risk of cardiovascular disease and frequently experience decreased physical function and health-related quality of life (HRQL). Studies in the early posttransplant period (<1 year) have shown the benefits of facility-based exercise training on physical function and HRQL, but have not evaluated the effects on metabolic risk factors. It remains unclear whether home-based exercise programs are feasible and can be delivered at a sufficient exercise dose to have effects on PTMS. This protocol outlines the methodology of a randomized controlled trial of a partly supervised home-based exercise program in lung transplant (LTx) and orthotopic liver transplant (OLT) recipients. Objective This study aims to evaluate the feasibility (ie, recruitment rate, program adherence, attrition, safety, and participant satisfaction) of a 12-week individualized, home-based aerobic and resistance training program in LTx and OLT recipients initiated 12 to 18 months after transplantation, and to assess estimates of intervention efficacy on metabolic risk factors, exercise self-efficacy, and HRQL. Methods In total, 20 LTx and 20 OLT recipients with ≥2 cardiometabolic risk factors at 12 to 18 months after transplantation will be randomized to an intervention (home-based exercise training) or control group. The intervention group will receive an individualized exercise prescription comprising aerobic and resistance training, 3 to 5 times a week for 12 weeks. Participants will meet on a weekly basis (via videoconference) with a qualified exercise professional who will supervise exercise progression, provide support, and support exercise self-efficacy. Participants in both study groups will receive a counseling session on healthy eating with a dietitian at the beginning of the intervention. For the primary aim, feasibility will be assessed through recruitment rate, program adherence, satisfaction, attrition, and safety parameters. Secondary outcomes will be measured at baseline and 12 weeks, including assessments of metabolic risk factors (ie, insulin resistance, abdominal obesity, blood pressure, and cholesterol), HRQL, and exercise self-efficacy. Descriptive statistics will be used to summarize program feasibility and effect estimates (means and 95% CIs) for sample size calculations in future trials. Results Enrollment started in July 2021. It is estimated that the study period will be 18 months, with data collection to be completed by December 2022. Conclusions A partly supervised home-based, individually tailored exercise program that promotes aerobic and resistance training and exercise self-efficacy may be an important intervention for improving the metabolic profile of LTx and OLT recipients with cardiometabolic risk factors. Thus, characterizing the feasibility and effect estimates of home-based exercise constitutes the first step in developing future clinical trials designed to reduce the high morbidity associated with PTMS. Trial Registration ClinicalTrials.gov NCT04965142; https://clinicaltrials.gov/ct2/show/NCT04965142 International Registered Report Identifier (IRRID) DERR1-10.2196/35700
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Affiliation(s)
- Dmitry Rozenberg
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Daniel Santa Mina
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.,Department of Anesthesia and Pain Management, University Health Network, Toronto, ON, Canada
| | - Sahar Nourouzpour
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Encarna Camacho Perez
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,GoodHope Ehlers-Danlos Syndrome Program, University Health Network, Toronto, ON, Canada
| | - Brooke Lyn Stewart
- Nutrition, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Lisa Wickerson
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Physical Therapy, University of Toronto, Toronto, ON, Canada
| | - Cynthia Tsien
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada.,Gastroenterology and Liver Transplantation, Temerty Faculty of Medicine, University Health Network, Toronto, ON, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada.,Gastroenterology and Liver Transplantation, Temerty Faculty of Medicine, University Health Network, Toronto, ON, Canada
| | - Josh Shore
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Meghan Aversa
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Minna Woo
- Endocrinology, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Sandra Holdsworth
- Canadian Donation and Transplantation Research Program, Edmonton, ON, Canada
| | - Karina Prevost
- Canadian Donation and Transplantation Research Program, Edmonton, ON, Canada
| | - Jeff Park
- Respirology and Lung Transplantation, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Amirhossein Azhie
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada.,Gastroenterology and Liver Transplantation, Temerty Faculty of Medicine, University Health Network, Toronto, ON, Canada
| | - Ella Huszti
- Biostatistics Research Unit, University Health Network, Toronto, ON, Canada
| | - Elizabeth McLeod
- Nutrition, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Sarah Dales
- Nutrition, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada.,Gastroenterology and Liver Transplantation, Temerty Faculty of Medicine, University Health Network, Toronto, ON, Canada
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23
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Wang R, Zhang Y, Fan J, Wang Z, Liu Y. Risk Factors for New-Onset Diabetes Mellitus After Heart Transplantation: A Nomogram Approach. Transplant Proc 2022; 54:762-768. [DOI: 10.1016/j.transproceed.2022.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 10/18/2022]
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24
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Lee CY, Wu MY, Chan HC, Chen TT, Hsu LY, Wu MS, Cherng YG. The Influence of Diabetes Mellitus on the Risks of End-Stage Kidney Disease and Mortality After Liver Transplantation. Transpl Int 2022; 35:10023. [PMID: 35185375 PMCID: PMC8842258 DOI: 10.3389/ti.2022.10023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022]
Abstract
This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and pre-existing DM group compared to those without DM group, respectively. The sensitivity analysis for the risk of ESKD and death also revealed the consistent result. Pre-existing DM has significant increase the risk of post-LT ESKD and mortality. The role of PLTDM should be explored to explain postoperative morbidity and mortality.
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Affiliation(s)
- Chung-Ying Lee
- Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Hsiu-Chen Chan
- Department of Pharmacy, Shuang Ho Hospital, New Taipei City, Taiwan
| | - Tzu-Ting Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
| | - Le-Yin Hsu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yih-Giun Cherng
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- *Correspondence: Yih-Giun Cherng,
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25
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Ducloux D, Courivaud C. Prevention of Post-Transplant Diabetes Mellitus: Towards a Personalized Approach. J Pers Med 2022; 12:116. [PMID: 35055431 PMCID: PMC8778007 DOI: 10.3390/jpm12010116] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/06/2022] [Accepted: 01/13/2022] [Indexed: 02/01/2023] Open
Abstract
Post-transplant diabetes is a frequent complication after transplantation. Moreover, patients suffering from post-transplant diabetes have increased cardiovascular morbidity and reduced survival. Pathogenesis mainly involves beta-cell dysfunction in presence of insulin resistance. Both pre- and post-transplant risk factors are well-described, and some of them may be corrected or prevented. However, the frequency of post-transplant diabetes has not decreased in recent years. We realized a critical appraisal of preventive measures to reduce post-transplant diabetes.
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Affiliation(s)
- Didier Ducloux
- CHU Besançon, Department of Nephrology, Dialysis and Renal Transplantation, Federation Hospitalo-Universitaire INCREASE, 25000 Besançon, France;
- UMR RIGHT 1098, INSERM-EFS-UFC, 1 Bd Fleming, 25000 Besançon, France
| | - Cécile Courivaud
- CHU Besançon, Department of Nephrology, Dialysis and Renal Transplantation, Federation Hospitalo-Universitaire INCREASE, 25000 Besançon, France;
- UMR RIGHT 1098, INSERM-EFS-UFC, 1 Bd Fleming, 25000 Besançon, France
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26
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Akintoye E, Alvarez P, Salih M, Sellke F, Briasoulis A. Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: A propensity-matched analysis. Clin Transplant 2022; 36:e14590. [PMID: 35018661 DOI: 10.1111/ctr.14590] [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: 12/16/2021] [Revised: 01/03/2022] [Accepted: 01/10/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND We investigated the current trends and outcomes of diabetic patients listed for heart transplants in the U.S. and provided a method for risk-stratification. METHODS Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetics, and waitlist mortality as well as post-transplant graft survival were compared between the two groups. Further risk-stratification of diabetic patients was done based on the risk factors that independently predict graft failure. RESULTS 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher in diabetic patients compared to non-diabetics (HR = 1.13 (95% CI = 1.04-1.22, p = 0.002). Over the study period, 5739 patients with diabetes were transplanted. In the propensity-matched cohorts of transplant recipients, the rate of graft failure was significantly higher for diabetic patients (23.3%) compared to non-diabetics (20.4%); HR = 1.17, 95% CI = 1.08-1.26, p<0.001. We identified 12 risk factors of graft failure among diabetic patients and developed a risk score that further risk-stratify these patients. Diabetic patients at low risk (score≤4) had similar graft survival as patients without diabetes (HR = 0.91, 95% CI = 0.82-1.01, p = 0.06). On the other hand, high-risk diabetic patients had worse graft survival compared to non-diabetics (HR = 1.52, 95% CI = 1.38-1.67, P<0.001). CONCLUSION Among patients with end-stage heart failure, pre-existing diabetes was associated with higher waitlist mortality and worse graft survival. However, with careful patient selection, graft survival is similar to those without diabetes. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Emmanuel Akintoye
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, United States
| | - Paulino Alvarez
- Division of Heart failure and Cardiac Transplantation, Cleveland Clinic, Cleveland, OH, United States
| | - Mohamed Salih
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Frank Sellke
- Department of Cardiothoracic Surgery, Brown University, Providence, RI, United States
| | - Alexandros Briasoulis
- Division of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa, IA, United States
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27
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Ahn JB, Bae S, Schnitzler M, Hess GP, Lentine KL, Segev DL, McAdams-DeMarco MA. Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age. Transplant Direct 2022; 8:e1260. [PMID: 34912947 PMCID: PMC8670588 DOI: 10.1097/txd.0000000000001260] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/08/2021] [Accepted: 10/13/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. METHODS Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). RESULTS Of 12 488, 28.3% recipients received ESW. The incidence rate for PTD was 13 per 100 person-y and lower among recipients who received ESW (11 per 100 person-y in ESW; 14 per 100 person-y in CSM). Overall, ESW was associated with lower risk of PTD compared with CSM (adjusted hazard ratio [aHR] = 0.720.790.86), but the risk differed by recipient age (P interaction = 0.09 for comparison between recipients aged 18-29 and those aged 30-54; P interaction = 0.01 for comparison between recipients aged 18-29 and those aged ≥55). ESW was associated with lower risk of PTD among recipients aged ≥55 (aHR = 0.620.710.81) and those aged 30-54 (aHR = 0.730.830.95), but not among recipients aged 18-29 (aHR = 0.811.181.72). Although recipients who received ESW had a higher risk of acute rejection across the age groups (adjusted odds ratio = 1.011.171.34), recipients with no PTD had a lower risk of mortality (aHR = 0.580.660.74). CONCLUSIONS The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.
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Affiliation(s)
- JiYoon B. Ahn
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sunjae Bae
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Mark Schnitzler
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO
| | - Gregory P. Hess
- Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia, PA
| | - Krista L. Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Mara A. McAdams-DeMarco
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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28
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Faucher Q, Jardou M, Brossier C, Picard N, Marquet P, Lawson R. Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus? Front Endocrinol (Lausanne) 2022; 13:898878. [PMID: 35872991 PMCID: PMC9302877 DOI: 10.3389/fendo.2022.898878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 06/06/2022] [Indexed: 11/13/2022] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM.
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Affiliation(s)
- Quentin Faucher
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
| | - Manon Jardou
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
| | - Clarisse Brossier
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
| | - Nicolas Picard
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
- Department of pharmacology, toxicology and pharmacovigilance, Centre Hospitalier Universitaire (CHU) Limoges, Limoges, France
| | - Pierre Marquet
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
- Department of pharmacology, toxicology and pharmacovigilance, Centre Hospitalier Universitaire (CHU) Limoges, Limoges, France
| | - Roland Lawson
- University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France
- *Correspondence: Roland Lawson,
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29
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Abu El Hawa AA, Bekeny JC, Dekker PK, Zolper EG, Tirrell AR, Kennedy CJ, Walters ET, Bovill JD, Fan KL, Attinger CE, Steinberg JS, Abrams PL, Evans KK. Surgical Management of Lower Extremity Wounds in the Solid Organ Transplant Patient Population: Surgeon Beware. Adv Wound Care (New Rochelle) 2022; 11:10-18. [PMID: 33487096 PMCID: PMC9831248 DOI: 10.1089/wound.2020.1380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Objective: To evaluate our institutional outcomes of surgical management of lower extremity (LE) wounds in the solid organ transplant recipient population. Approach: An 8-year retrospective review was conducted for all solid organ transplantation (SOT) recipients with LE wounds necessitating surgical management at our tertiary limb salvage center. Outcomes of interest included wound healing, surgical treatment, progression to amputation, and amputation level. Factors contributing to amputation progression were analyzed. The article adheres to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results: Sixty-four SOT recipients underwent surgical management for their LE wounds between 2010 and 2018. Median number of surgeries per patient was 5 (interquartile range = 2-8); 47 of 64 patients (73.4%) underwent amputation, and 17 of 64 patients (26.6%) underwent nonamputation surgical management. In the amputation group, the majority of primary amputations were minor (42/47, 89.4%); 24 of 42 (57.1%) patients progressed to a higher amputation level, 16 of 42 (38.1%) healed after their index procedure, and 2 of 42 (4.8%) were lost to follow-up (LTFU) after their primary minor amputation. Five of 47 (10.6%) patients undergoing amputations required primary below-knee amputations. In the nonamputation group, 15 of 17 (88.2%) healed, 1 of 17 (5.9%) expired, and 1 of 17 (5.9%) was LTFU. Innovation: To identify the outcomes of patients undergoing surgical management for LE wounds after SOT and elucidate clinical factors that impact the rate of limb salvage. Conclusions: This is the first comprehensive analysis of LE wounds in the transplant population. Our analysis indicates high rates of failed minor amputation, and frequent progression to major amputation in SOT patients. Preexisting comorbidities and immunosuppressive regimens complicate limb salvage; therefore, further research is warranted to optimize surgical LE wound management in this population.
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Affiliation(s)
| | - Jenna C. Bekeny
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Paige K. Dekker
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Elizabeth G. Zolper
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Abigail R. Tirrell
- Georgetown University School of Medicine, Washington, District of Columbia, USA
| | - Christopher J. Kennedy
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Elliot T. Walters
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - John D. Bovill
- Georgetown University School of Medicine, Washington, District of Columbia, USA
| | - Kenneth L. Fan
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Christopher E. Attinger
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - John S. Steinberg
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Peter L. Abrams
- Department of Transplant Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Karen K. Evans
- Department of Plastic and Reconstructive Surgery and MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,Correspondence: Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA .
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30
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Maliakkal B, Satapathy SK. New onset diabetes mellitus after liver transplantation. Hepatobiliary Surg Nutr 2021; 10:724-727. [PMID: 34760986 DOI: 10.21037/hbsn-21-214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 06/08/2021] [Indexed: 11/06/2022]
Affiliation(s)
| | - Sanjaya K Satapathy
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY, USA
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31
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Lin H, Yan J, Yuan L, Qi B, Zhang Z, Zhang W, Ma A, Ding F. Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data. Diabetol Metab Syndr 2021; 13:126. [PMID: 34717725 PMCID: PMC8557540 DOI: 10.1186/s13098-021-00742-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 10/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) occurs in 10-30% of kidney transplant recipients. However, its impact on mortality and graft survival is still ambiguous. Therefore, the current study aimed to analyze if PTDM increases mortality and graft failure by pooling multivariable-adjusted data from individual studies. METHODS PubMed, Embase, and CENTRAL, and Google Scholar were searched for studies comparing mortality and graft failure between PTDM and non-diabetic patients. Multivariable-adjusted hazard ratios (HR) were pooled in a random-effects model. RESULTS Fourteen retrospective studies comparing 9872 PTDM patients with 65,327 non-diabetics were included. On pooled analysis, we noted a statistically significant increase in the risk of all-cause mortality in patients with PTDM as compared to non-diabetics (HR: 1.67 95% CI 1.43, 1.94 I2 = 57% p < 0.00001). The meta-analysis also indicated a statistically significant increase in the risk of graft failure in patients with PTDM as compared to non-diabetics (HR: 1.35 95% CI 1.15, 1.58 I2 = 78% p = 0.0002). Results were stable on sensitivity analysis. There was no evidence of publication bias on funnel plots. CONCLUSION Kidney transplant patients developing PTDM have a 67% increased risk of all-cause mortality and a 35% increased risk of graft failure. Further studies are needed to determine the exact cause of increased mortality and the mechanism involved in graft failure.
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Affiliation(s)
- Hailing Lin
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Jiqiang Yan
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Lei Yuan
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Beibei Qi
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Zhujing Zhang
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Wanlu Zhang
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Aihua Ma
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China
| | - Fuwan Ding
- Department of Endocrinology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, No. 75 Juchang Road, Yancheng, Jiangsu, China.
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32
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Ben-David E, Hull R, Banerjee D. Diabetes mellitus in dialysis and renal transplantation. Ther Adv Endocrinol Metab 2021; 12:20420188211048663. [PMID: 34631007 PMCID: PMC8495524 DOI: 10.1177/20420188211048663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/29/2021] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.
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Affiliation(s)
- Eyal Ben-David
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Hull
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Debasish Banerjee
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, Room G2.113, Second Floor, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
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33
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Oka A, Ishimura N, Ishihara S. A New Dawn for the Use of Artificial Intelligence in Gastroenterology, Hepatology and Pancreatology. Diagnostics (Basel) 2021; 11:1719. [PMID: 34574060 PMCID: PMC8468082 DOI: 10.3390/diagnostics11091719] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/17/2021] [Accepted: 09/17/2021] [Indexed: 12/15/2022] Open
Abstract
Artificial intelligence (AI) is rapidly becoming an essential tool in the medical field as well as in daily life. Recent developments in deep learning, a subfield of AI, have brought remarkable advances in image recognition, which facilitates improvement in the early detection of cancer by endoscopy, ultrasonography, and computed tomography. In addition, AI-assisted big data analysis represents a great step forward for precision medicine. This review provides an overview of AI technology, particularly for gastroenterology, hepatology, and pancreatology, to help clinicians utilize AI in the near future.
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Affiliation(s)
- Akihiko Oka
- Department of Internal Medicine II, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (N.I.); (S.I.)
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Mohapatra A, Valson AT, Annapandian VM, David VG, Alexander S, Jacob S, Kakde S, Kumar S, Devasia A, Vijayakumar TS, Tamilarasi V, Jacob CK, Basu G, John GT, Varughese S. Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras. Pediatr Transplant 2021; 25:e13973. [PMID: 33463876 PMCID: PMC7615901 DOI: 10.1111/petr.13973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 12/21/2020] [Accepted: 12/24/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.
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Affiliation(s)
- Anjali Mohapatra
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T. Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | | | | | - Shibu Jacob
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Shailesh Kakde
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Santosh Kumar
- Department of Urology, Christian Medical College, Vellore, India
| | - Antony Devasia
- Department of Urology, Christian Medical College, Vellore, India
| | | | | | | | - Gopal Basu
- Department of Nephrology, Christian Medical College, Vellore, India
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Aziz F. New Onset Diabetes Mellitus after Transplant: The Challenge Continues. KIDNEY360 2021; 2:1212-1214. [PMID: 35369659 PMCID: PMC8676398 DOI: 10.34067/kid.0004042021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 06/23/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, Wisconsin
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36
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Schwaiger E, Krenn S, Kurnikowski A, Bergfeld L, Pérez-Sáez MJ, Frey A, Topitz D, Bergmann M, Hödlmoser S, Bachmann F, Halleck F, Kron S, Hafner-Giessauf H, Eller K, Rosenkranz AR, Crespo M, Faura A, Tura A, Song PXK, Port FK, Pascual J, Budde K, Ristl R, Werzowa J, Hecking M. Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial. J Am Soc Nephrol 2021; 32:2083-2098. [PMID: 34330770 PMCID: PMC8455276 DOI: 10.1681/asn.2021010127] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/03/2021] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Post-transplantation diabetes mellitus (PTDM) might be preventable. METHODS This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant. RESULTS In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24. CONCLUSIONS At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.Clinical Trial registration number: NCT03507829.
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Affiliation(s)
- Elisabeth Schwaiger
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine II, Kepler University Hospital, Linz, Austria
| | | | - Amelie Kurnikowski
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Leon Bergfeld
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Alexander Frey
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine and Gastroenterology, Hospital Vienna North, Vienna, Austria
| | - David Topitz
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Pediatrics and Adolescent Medicine, Clinic Ottakring, Vienna, Austria
| | - Michael Bergmann
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Pneumology, Clinic Ottakring, Vienna, Austria
| | - Sebastian Hödlmoser
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Epidemiology, Medical University of Vienna, Vienna, Austria
| | - Friederike Bachmann
- 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
| | - Susanne Kron
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | | | | | | | - Anna Faura
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Andrea Tura
- Metabolic Unit, CNR Institute of Neuroscience, Padova, Italy
| | - Peter X K Song
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | | | - Julio Pascual
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | | | - Robin Ristl
- Center for Medical Statistics, Informatics and Intelligent Systems, Vienna, Austria
| | - Johannes Werzowa
- 1st Medical Department, Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, Vienna, Austria
| | - Manfred Hecking
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Ertuglu LA, Porrini E, Hornum M, Demiray A, Afsar B, Ortiz A, Covic A, Rossing P, Kanbay M. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation. Transpl Int 2021; 34:1341-1359. [PMID: 33880815 DOI: 10.1111/tri.13883] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/22/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP-1RA may counteract some of the driving forces for PTDM, as calcineurin-induced β cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP-1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized-controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP-1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre-existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.
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Affiliation(s)
- Lale A Ertuglu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Esteban Porrini
- Red de Investigación Renal (REDINREN), Instituto Carlos III-FEDER, Tenerife, Spain.,Department of Medicine, Hospital Universitario de Canarias, Tenerife, Spain.,Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Atalay Demiray
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Alberto Ortiz
- IIS-Fundacion Jimenez Diaz, Department of Medicine, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Peter Rossing
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Copenhagen, Denmark
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
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Lawendy B, Srinathan S, Kotha S, Gomes C, Misra S, Yu J, Orchanian-Cheff A, Tomlinson G, Bhat M. Systematic review and meta-analysis of post-transplant diabetes mellitus in liver transplant recipients. Clin Transplant 2021; 35:e14340. [PMID: 34033142 DOI: 10.1111/ctr.14340] [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: 08/09/2020] [Revised: 04/17/2021] [Accepted: 04/26/2021] [Indexed: 01/04/2023]
Abstract
Post-transplant diabetes mellitus (PTDM) compromises long-term survival in liver transplant (LT) recipients. The aim of this study was to determine incidence of PTDM after LT and risk factors associated with it. A literature search was conducted, and prospective studies that reported on the incidence of PTDM in LT adult patients on tacrolimus, sirolimus, or cyclosporine were included. We performed random effects meta-analyses for the incidence of PTDM stratified by immunosuppressant and time period. Of 9817 articles identified, 26 studies were included in the qualitative analysis and 21 studies were eligible for the quantitative analysis representing 79 559 LT recipients in 32 separate treatment arms. The proportion of patients who developed PTDM by two-three years was 0.15 (95% CI: 0.10-0.24) for cyclosporine, 0.23 (95% CI: 0.14-0.36) for tacrolimus, and 0.27 (95% CI: 0.23-0.30) for sirolimus. CONCLUSION: Our results showed that sirolimus-based immunosuppression was associated with a higher incidence of PTDM than tacrolimus or cyclosporine at two-three years. However, there were only two studies that compared all three drugs which is a limitation of the study and requires more studies with patients on sirolimus. Recipient factors increasing the risk of PTDM are older age, male sex, and high BMI.
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Affiliation(s)
- Bishoy Lawendy
- University of Toronto, Toronto, ON, Canada.,Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Sujitha Srinathan
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,University of Ottawa, Ottawa, ON, Canada
| | | | - Charlene Gomes
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Jeffrey Yu
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, ON, Canada
| | - George Tomlinson
- Institute of Health Policy, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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39
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Malik RF, Jia Y, Mansour SG, Reese PP, Hall IE, Alasfar S, Doshi MD, Akalin E, Bromberg JS, Harhay MN, Mohan S, Muthukumar T, Schröppel B, Singh P, Weng FL, Thiessen Philbrook HR, Parikh CR. Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study. KIDNEY360 2021; 2:1296-1307. [PMID: 35369651 PMCID: PMC8676388 DOI: 10.34067/kid.0000862021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/01/2021] [Indexed: 02/06/2023]
Abstract
Background De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. Methods In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Results Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. Conclusions PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.
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Affiliation(s)
- Rubab F. Malik
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yaqi Jia
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sherry G. Mansour
- Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut,Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Peter P. Reese
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Isaac E. Hall
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
| | - Sami Alasfar
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mona D. Doshi
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
| | - Enver Akalin
- Kidney Transplant Program, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Jonathan S. Bromberg
- Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland,Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Meera N. Harhay
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania,Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania,Tower Health Transplant Institute, Tower Health System, West Reading, Pennsylvania
| | - Sumit Mohan
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York,Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, New York, New York
| | - Thangamani Muthukumar
- Department of Medicine, Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York,Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | | | - Pooja Singh
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Francis L. Weng
- Saint Barnabas Medical Center, RWJBarnabas Health, Livingston, New Jersey
| | | | - Chirag R. Parikh
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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40
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Chowdhury TA, Wahba M, Mallik R, Peracha J, Patel D, De P, Fogarty D, Frankel A, Karalliedde J, Mark PB, Montero RM, Pokrajac A, Zac-Varghese S, Bain SC, Dasgupta I, Banerjee D, Winocour P, Sharif A. Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation. Diabet Med 2021; 38:e14523. [PMID: 33434362 DOI: 10.1111/dme.14523] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/24/2020] [Accepted: 01/09/2021] [Indexed: 01/06/2023]
Abstract
Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).
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Affiliation(s)
| | | | | | | | - Dipesh Patel
- Diabetes & Endocrinology, Royal Free NHS foundation Trust, UCL, London, UK
| | | | | | | | - Janaka Karalliedde
- Guy's and St Thomas NHS Foundation Trust and King's College London, London, UK
| | | | | | - Ana Pokrajac
- West Hertfordshire Hospitals NHS Trust, Watford, UK
| | | | | | - Indranil Dasgupta
- Heartlands Hospital, Birmingham, UK
- Warwick Medical School, Warwick, UK
| | - Debasish Banerjee
- Renal and Transplant Unit, St George's University Hospitals NHS Foundation Trust and MCSRI, St George's University of London, London, UK
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41
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Bhadada SK, Pal R. Post-liver transplantation diabetes mellitus — a clinical challenge for diabetologists? Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00955-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Supabphol S, Seubwai W, Wongkham S, Saengboonmee C. High glucose: an emerging association between diabetes mellitus and cancer progression. J Mol Med (Berl) 2021; 99:1175-1193. [PMID: 34036430 DOI: 10.1007/s00109-021-02096-w] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 04/16/2021] [Accepted: 05/18/2021] [Indexed: 12/11/2022]
Abstract
The association of cancer and diabetes mellitus (DM) has been studied for decades. Hyperglycemia and the imbalance of hormones are factors that contribute to the molecular link between DM and carcinogenesis and cancer progression. Hyperglycemia alone or in combination with hyperinsulinemia are key factors that promote cancer aggressiveness. Many preclinical studies suggest that high glucose induces abnormal energy metabolism and aggressive cancer via several mechanisms. As evidenced by clinical studies, hyperglycemia is associated with poor clinical outcomes in patients who have comorbid DM. The prognoses of cancer patients with DM are improved when their plasma glucose levels are controlled. This suggests that high glucose level maybe be involved in the molecular mechanism that causes the link between DM and cancer and may also be useful for prognosis of cancer progression. This review comprehensively summarizes the evidence from recent pre-clinical and clinical studies of the impact of hyperglycemia on cancer advancement as well as the underlying molecular mechanism for this impact. Awareness among clinicians of the association between hyperglycemia or DM and cancer progression may improve cancer treatment outcome in patients who have DM.
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Affiliation(s)
- Suangson Supabphol
- The Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Wunchana Seubwai
- Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.,Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Sopit Wongkham
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.,Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.,Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Charupong Saengboonmee
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand. .,Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. .,Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
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Montada-Atin T, Prasad GVR. Recent advances in new-onset diabetes mellitus after kidney transplantation. World J Diabetes 2021; 12:541-555. [PMID: 33995843 PMCID: PMC8107982 DOI: 10.4239/wjd.v12.i5.541] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/05/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
A common challenge in managing kidney transplant recipients (KTR) is post-transplant diabetes mellitus (PTDM) or diabetes mellitus (DM) newly diagnosed after transplantation, in addition to known pre-existing DM. PTDM is an important risk factor for post-transplant cardiovascular (CV) disease, which adversely affects patient survival and quality of life. CV disease in KTR may manifest as ischemic heart disease, heart failure, and/or left ventricular hypertrophy. Available therapies for PTDM include most agents currently used to treat type 2 diabetes. More recently, the use of sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase 4 inhibitors (DPP4i) has cautiously extended to KTR with PTDM, even though KTR are typically excluded from large general population clinical trials. Initial evidence from observational studies seems to indicate that SGLT2i, GLP-1 RA, and DPP4i may be safe and effective for glycemic control in KTR, but their benefit in reducing CV events in this otherwise high-risk population remains unproven. These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status, pre-existing burden of peripheral vascular disease, urinary tract infections due to immunosuppression and a surgically altered urinary tract, erythrocytosis from calcineurin inhibitors, and reduced kidney function from acute or chronic rejection.
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Affiliation(s)
- Tess Montada-Atin
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
| | - G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto M5C 2T2, Canada
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Weinrauch LA, D'Elia JA. Renal transplant outcomes and diabetes. BMJ Open Diabetes Res Care 2021; 9:9/1/e002294. [PMID: 33962974 PMCID: PMC8108671 DOI: 10.1136/bmjdrc-2021-002294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/11/2021] [Indexed: 11/17/2022] Open
Affiliation(s)
- Larry A Weinrauch
- Kidney and Hypertension Section, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - John A D'Elia
- Kidney and Hypertension Section, Joslin Diabetes Center, Boston, Massachusetts, USA
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Rysz J, Franczyk B, Radek M, Ciałkowska-Rysz A, Gluba-Brzózka A. Diabetes and Cardiovascular Risk in Renal Transplant Patients. Int J Mol Sci 2021; 22:3422. [PMID: 33810367 PMCID: PMC8036743 DOI: 10.3390/ijms22073422] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/05/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Maciej Radek
- Department of Neurosurgery, Surgery of Spine and Peripheral Nerves, Medical University of Lodz, 90-549 Lodz, Poland;
| | | | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
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Munshi VN, Saghafian S, Cook CB, Aradhyula SV, Chakkera HA. Use of Imputation and Decision Modeling to Improve Diagnosis and Management of Patients at Risk for New-Onset Diabetes After Transplantation. Ann Transplant 2021; 26:e928624. [PMID: 33723204 PMCID: PMC7980500 DOI: 10.12659/aot.928624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 01/06/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a complication of solid organ transplantation. We sought to determine the extent to which NODAT goes undiagnosed over the course of 1 year following transplantation, analyze missed or later-diagnosed cases of NODAT due to poor hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) collection, and to estimate the impact that improved NODAT screening metrics may have on long-term outcomes. MATERIAL AND METHODS This was a retrospective study utilizing 3 datasets from a single center on kidney, liver, and heart transplantation patients. Retrospective analysis was supplemented with an imputation procedure to account for missing data and project outcomes under perfect information. In addition, the data were used to inform a simulation model used to estimate life expectancy and cost-effectiveness of a hypothetical intervention. RESULTS Estimates of NODAT incidence increased from 27% to 31% in kidney transplantation patients, from 31% to 40% in liver transplantation patients, and from 45% to 67% in heart transplantation patients, when HbA1c and FBG were assumed to be collected perfectly at all points. Perfect screening for kidney transplantation patients was cost-saving, while perfect screening for liver and heart transplantation patients was cost-effective at a willingness-to-pay threshold of $100 000 per life-year. CONCLUSIONS Improved collection of HbA1c and FBG is a cost-effective method for detecting many additional cases of NODAT within the first year alone. Additional research into both improved glucometric monitoring as well as effective strategies for mitigating NODAT risk will become increasingly important to improve health in this population.
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Affiliation(s)
- Vidit N. Munshi
- Department of Health Policy, Harvard University, Cambridge, MA, U.S.A
| | | | - Curtiss B. Cook
- Department of Endocrinology, Mayo Clinic, Scottsdale, AZ, U.S.A
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Ponticelli C, Favi E, Ferraresso M. New-Onset Diabetes after Kidney Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:250. [PMID: 33800138 PMCID: PMC7998982 DOI: 10.3390/medicina57030250] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/25/2021] [Accepted: 03/05/2021] [Indexed: 02/07/2023]
Abstract
New-onset diabetes mellitus after transplantation (NODAT) is a frequent complication in kidney allograft recipients. It may be caused by modifiable and non-modifiable factors. The non-modifiable factors are the same that may lead to the development of type 2 diabetes in the general population, whilst the modifiable factors include peri-operative stress, hepatitis C or cytomegalovirus infection, vitamin D deficiency, hypomagnesemia, and immunosuppressive medications such as glucocorticoids, calcineurin inhibitors (tacrolimus more than cyclosporine), and mTOR inhibitors. The most worrying complication of NODAT are major adverse cardiovascular events which represent a leading cause of morbidity and mortality in transplanted patients. However, NODAT may also result in progressive diabetic kidney disease and is frequently associated with microvascular complications, eventually determining blindness or amputation. Preventive measures for NODAT include a careful assessment of glucose tolerance before transplantation, loss of over-weight, lifestyle modification, reduced caloric intake, and physical exercise. Concomitant measures include aggressive control of systemic blood pressure and lipids levels to reduce the risk of cardiovascular events. Hypomagnesemia and low levels of vitamin D should be corrected. Immunosuppressive strategies limiting the use of diabetogenic drugs are encouraged. Many hypoglycemic drugs are available and may be used in combination with metformin in difficult cases. In patients requiring insulin treatment, the dose and type of insulin should be decided on an individual basis as insulin requirements depend on the patient's diet, amount of exercise, and renal function.
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Affiliation(s)
- Claudio Ponticelli
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, 20122 Milan, Italy
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, 20122 Milan, Italy
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Alghanem SS, Soliman MM, Alibrahim AA, Gheith O, Kenawy AS, Awad A. Monitoring Tacrolimus Trough Concentrations During the First Year After Kidney Transplantation: A National Retrospective Cohort Study. Front Pharmacol 2021; 11:566638. [PMID: 33658922 PMCID: PMC7919378 DOI: 10.3389/fphar.2020.566638] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 10/02/2020] [Indexed: 01/03/2023] Open
Abstract
Background: There is a lack of data in the literature on the evaluation of tacrolimus (TAC) dosage regimen and monitoring after kidney transplantation (KT) in Kuwait. The aim of the present study was to evaluate TAC dosing in relation to the hospital protocol, the achievement of target TAC trough concentration (C0), the prevalence of TAC side effects (SEs), namely, posttransplant diabetes mellitus (PTDM), denovo hypertension (HTN), and dyslipidemia, and factors associated with the occurrence of these SEs among KT recipients. Methods: A retrospective study was conducted among 298 KT recipients receiving TAC during the first year of PT. Descriptive and multivariate logistic regression analyses were used. Results: The initial TAC dosing as per the local hospital protocol was prescribed for 28.2% of patients. The proportion of patients who had C0 levels within the target range increased from 31.5 to 60.3% during week 1 through week 52. Among patients who did not have HTN, DM, or dyslipidemia before using TAC, 78.6, 35.2, and 51.9% of them were prescribed antihypertensive, antidiabetic, and antilipidemic medications during the follow-up period. Age of ≥40 years was significantly associated with the development of de novo HTN, dyslipidemia, and PTDM (p < 0.05). High TAC trough concentration/daily dose (C0/D) ratio was significantly associated with the development of PTDM (p < 0.05). Conclusion: Less than two-fifths of patients achieved target TAC C0 levels during the first month of PT. Side effects were more common in older patients. These findings warrant efforts to implement targeted multifaceted interventions to improve TAC prescribing and monitoring after KT.
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Affiliation(s)
- Sarah S Alghanem
- Department of Pharmacy Practice, Kuwait University, Kuwait City, Kuwait
| | - Moetaza M Soliman
- Department of Pharmacy Practice, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Ali A Alibrahim
- Pharmacy Department, Manahi Al-Osaimi Health Centre, Ministry of Health, Kuwait City, Kuwait
| | - Osama Gheith
- Nephrology Department, Hamed Al-Essa Organ Transplant Centre, Ministry of Health, Kuwait City, Kuwait.,Urology and Nephrology Centre, Mansoura University, Mansoura, Egypt
| | - Ahmed S Kenawy
- Pharmacy Department, Hamed Al-Essa Organ Transplant Centre, Ministry of Health, Kuwait city, Kuwait
| | - Abdelmoneim Awad
- Department of Pharmacy Practice, Kuwait University, Kuwait City, Kuwait
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Chin YH, Tan HQM, Ng CH, Tan DJH, Lin SY, Huang DQ, Khoo CM, Muthiah MD. A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation. J Clin Med 2021; 10:jcm10051045. [PMID: 33802465 PMCID: PMC7959476 DOI: 10.3390/jcm10051045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/08/2021] [Accepted: 02/24/2021] [Indexed: 12/29/2022] Open
Abstract
NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.
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Affiliation(s)
- Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Hon Qin Marcus Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Correspondence: or (C.H.N.); (M.D.M.)
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
- Correspondence: or (C.H.N.); (M.D.M.)
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Podestà MA, Cucchiari D, Ciceri P, Messa P, Torregrosa JV, Cozzolino M. Cardiovascular calcifications in kidney transplant recipients. Nephrol Dial Transplant 2021; 37:2063-2071. [PMID: 33620476 DOI: 10.1093/ndt/gfab053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Vascular and valvular calcifications are highly prevalent in kidney transplant recipients and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uremia-associated metabolic derangements, kidney transplant recipients are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in kidney transplant recipients, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.
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Affiliation(s)
- Manuel Alfredo Podestà
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
| | - David Cucchiari
- Nephrology and Renal Transplant Department, Hospital Clínic, Barcelona, Spain
| | - Paola Ciceri
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Piergiorgio Messa
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
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