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Luo B, Zhong S, Wang X, Guo P, Hou Y, Di W. Management of blood lipids in post-kidney transplant patients: a systematic review and network meta-analysis. Front Pharmacol 2024; 15:1440875. [PMID: 39439889 PMCID: PMC11493609 DOI: 10.3389/fphar.2024.1440875] [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: 05/30/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
Introduction The primary objective of this systematic review was to provide an overview of the efficacy and safety of various lipid-lowering therapies in patients post-kidney transplant (PKT), given the limited existing literature. Considering the restricted number of available studies, this work aimed to summarize the existing evidence regarding the effectiveness of different lipid-lowering treatments in PKT patients. The effects of various lipid-lowering therapeutic regimens on lipid levels were compared, and their safety was assessed, with the heterogeneity of treatment protocols acknowledged. Material and Methods Randomized controlled trials investigating different treatment regimens (DTRs) for regulating lipid levels in PKT patients were systematically retrieved from PubMed, Cochrane Library, and Embase, from inception to March 2024. Literature quality was assessed employing the Cochrane risk of bias assessment tool. Data analysis and graphical representation were performed employing RevMan5.3 and Stata 20.0. The surface under the cumulative ranking area (SUCRA) compared the effects of DTRs on lipid profiles, incidence of adverse events, and all-cause mortality in PKT patients. Results Fifteen studies were included, comprising 5,768 PKT patients and involving 9 treatment regimens. The results revealed that, for changes in high-density lipoprotein cholesterol (HDL-C), the SUCRA rankings from highest to lowest among PKT patients receiving DTRs were statins + ezetimibe (70%), placebo (61.5%), fibrates (57.2%), statins (44.1%), and fish oil (17.3%). Regarding changes in low-DL-C (LDL-C), the SUCRA rankings from highest to lowest among PKT patients receiving DTRs were statins (68.2%), statins + ezetimibe (67.5%), fish oil (53.4%), fibrates (34.5%), and placebo (26.5%). For the change in total cholesterol (TC) levels, a network meta-analysis (NMA) revealed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for TC change were statins + ezetimibe (97.6%), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) (74.3%), fish oil (64.3%), statins (61.6%), fibrates (47.2%), placebo (31.6%), calcineurin phosphatase inhibitors (11.9%), and immunosuppressants (11.4%). Regarding the change in triglyceride (TG) levels, a NMA showed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for TG change were fibrates (99.9%), statins (68.9%), PCSK9 inhibitors (66.6%), statins + ezetimibe (55.1%), placebo (49.2%), fish oil (45.0%), immunosuppressants (7.8%), and calcineurin phosphatase inhibitors (7.6%). For the occurrence of kidney transplant failure, a NMA revealed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for reducing the incidence of kidney transplant failure were PCSK9 inhibitors (69.0%), calcineurin phosphatase inhibitors (63.0%), statins (61.5%), placebo (55.1%), steroids (51.8%), immunosuppressants (27.1%), and fibrates (22.5%). Regarding all-cause mortality, a NMA showed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for reducing all-cause mortality were PCSK9 inhibitors (90.5%), statins (55.8%), and placebo (3.7%). Conclusion In reducing lipid levels in PKT patients, combination therapy with statins and ezetimibe demonstrated notable advantages and higher effectiveness. PCSK9 inhibitors exhibited greater advantages in reducing adverse events and mortality rates in PKT patients, with higher safety.
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Affiliation(s)
- Bohan Luo
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Shan Zhong
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Xiaoxiao Wang
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Pu Guo
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yifu Hou
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Wenjia Di
- Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Alasfar S, Me HM, Budhiraja P. Approach to Late Noninfectious Post-Transplant Complications. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:436-449. [PMID: 39232614 DOI: 10.1053/j.akdh.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/16/2024] [Accepted: 05/24/2024] [Indexed: 09/06/2024]
Abstract
The management of noninfectious complications in kidney transplant recipients includes a broad spectrum of conditions, including metabolic issues, cardiovascular diseases, and malignancies, each presenting unique challenges for nephrologists managing these patients. Unlike infectious complications, these noninfectious issues require nuanced, multidisciplinary approaches for prevention, diagnosis, and management, emphasizing the need for personalized care plans. Cardiovascular disease is particularly significant, standing as the primary cause of death post-transplantation, with recent data indicating an overtaking of cancer death rates over infections among kidney transplant recipients. The intricacies of managing these patients, influenced by the burden of kidney disease and immunosuppression, highlight the importance of a collaborative care model. Although nephrologists may not directly treat all these conditions, their understanding of the unique aspects of transplant recipients is crucial. They play a pivotal role in coordinating care with specialists such as cardiologists, endocrinologists, hematologists, and oncologists, ensuring comprehensive management that addresses these specific post-transplant complications. This review discusses the epidemiology, underlying mechanisms, clinical manifestations, and management strategies of various noninfectious complications post-kidney transplant, with a focus on cardiovascular, metabolic, oncologic, and hematologic complications.
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Affiliation(s)
- Sami Alasfar
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ.
| | - Hay Me Me
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ
| | - Pooja Budhiraja
- Mayo Clinic Arizona, Division of Nephrology, Department of Medicine, Phoenix, AZ
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Liu X, Shen J, Yan H, Hu J, Liao G, Liu D, Zhou S, Zhang J, Liao J, Guo Z, Li Y, Yang S, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Luo P, Zhao M, Liu Y. Posttransplant complications: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2024; 5:e669. [PMID: 39224537 PMCID: PMC11366828 DOI: 10.1002/mco2.669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.
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Affiliation(s)
- Xiaoyou Liu
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Junyi Shen
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hongyan Yan
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jianmin Hu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Guorong Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ding Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Song Zhou
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jie Zhang
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jun Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Zefeng Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yuzhu Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Siqiang Yang
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Shichao Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hua Chen
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ying Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Min Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Lipei Fan
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Liuyang Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Peng Luo
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ming Zhao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yongguang Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
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Zheng WC, Evans N, Dinh D, Bloom JE, Brennan AL, Ball J, Lefkovits J, Shaw JA, Reid CM, Chan W, Stub D. Clinical Outcomes of Renal Transplant Recipients Undergoing Percutaneous Coronary Intervention. Heart Lung Circ 2024; 33:998-1008. [PMID: 38565437 DOI: 10.1016/j.hlc.2024.01.033] [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: 11/28/2023] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 04/04/2024]
Abstract
BACKGROUND Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. METHOD Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RESULTS RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality. CONCLUSIONS RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.
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Affiliation(s)
- Wayne C Zheng
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia
| | - Nicole Evans
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia
| | - Diem Dinh
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia
| | - Jason E Bloom
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, Vic, Australia
| | - Angela L Brennan
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia
| | - Jocasta Ball
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, Vic, Australia
| | - Jeffrey Lefkovits
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; Department of Cardiology, The Royal Melbourne Hospital, Melbourne, Vic, Australia
| | - James A Shaw
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia
| | - Christopher M Reid
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; School of Population Health, Curtin University, Perth, WA, Australia
| | - William Chan
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, Vic, Australia; Department of Medicine, The University of Melbourne, Melbourne, Vic, Australia
| | - Dion Stub
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia.
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5
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van den Born JC, Meziyerh S, Vart P, Bakker SJL, Berger SP, Florquin S, de Fijter JW, Gomes-Neto AW, Idu MM, Pol RA, Roelen DL, van Sandwijk MS, de Vries DK, de Vries APJ, Bemelman FJ, Sanders JSF. Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial. Transplantation 2024; 108:556-566. [PMID: 37650722 DOI: 10.1097/tp.0000000000004776] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
BACKGROUND Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. METHODS The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. RESULTS A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m 2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m 2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m 2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection ( P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. CONCLUSIONS Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
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Affiliation(s)
- Joost C van den Born
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Soufian Meziyerh
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
- Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Priya Vart
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stefan P Berger
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Sandrine Florquin
- Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Johan W de Fijter
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - António W Gomes-Neto
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Mirza M Idu
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Robert A Pol
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Dave L Roelen
- Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
| | - Marit S van Sandwijk
- Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Dorottya K de Vries
- Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Aiko P J de Vries
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
- Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Frederike J Bemelman
- Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Jan Stephan F Sanders
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Okamoto T, Hatakeyama S, Hamaya T, Matsuura T, Saito M, Nishida H, Maita S, Murakami R, Tomita H, Saitoh H, Tsuchiya N, Habuchi T, Obara W, Ohyama C. Impact of timing of rejection episode on cardiovascular events in living donor kidney transplantation: a multicenter retrospective study. J Nephrol 2023; 36:2613-2620. [PMID: 37938544 DOI: 10.1007/s40620-023-01811-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/14/2023] [Indexed: 11/09/2023]
Abstract
BACKGROUND Cardiovascular diseases are still highly prevalent after kidney transplantation. However, little is known about the impact of the timing of rejection episodes on cardiovascular disease. The study aimed to analyze the influence of the timing of rejection episodes on cardiovascular events in recipients of living donor kidney transplantation. METHODS We studied 572 living donor kidney transplant recipients from the Michinoku Renal Transplant Network (MRTN), which includes 6 centers in the Tohoku region of Japan. Fine-Gray proportional hazards regression analysis with time-dependent variables was used to assess the effect of rejection episode on cardiovascular events. Recipients were divided into three groups: those without rejection (non-rejection, 370 patients), rejection within 6 months after transplantation (early rejection, 99 patients), and rejection after 6 months (late rejection, 103 patients). The effect of timing on cardiovascular events was evaluated using Fine-Gray proportional hazards regression analysis. RESULTS During a median follow-up of 77 months, 70 patients experienced cardiovascular events. Rejection episodes were significantly associated with cardiovascular events (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.26-3.43, P = 0.004), along with age and dialysis vintage. The 5-year cumulative incidence of cardiovascular events was significantly higher in the late rejection group than in the early rejection group (15% vs. 3.3%, P = 0.021). However, no significant difference in 5-year cumulative cardiovascular event incidence was observed between the early rejection and non-rejection groups. Late rejection was significantly associated with cardiovascular events (HR: 2.40, 95% CI: 1.38-4.18, P = 0.002), whereas early rejection was not significantly correlated with cardiovascular event risk (HR: 1.18, P = 0.670). CONCLUSIONS Rejections occurring more than 6 months after transplantation is significantly associated with risk of cardiovascular events. TRIAL REGISTRATION NUMBER 2019-099-1, date of registration; 3 Dec. 2019, retrospectively registered.
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Affiliation(s)
- Teppei Okamoto
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan.
| | - Tomoko Hamaya
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Tomohiko Matsuura
- Department of Urology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Morioka, Iwate, 028-3694, Japan
| | - Mitsuru Saito
- Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan
| | - Hayato Nishida
- Department of Urology, Yamagata University School of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9885, Japan
| | - Shinya Maita
- Department of Urology, Iwate Prefectural Isawa Hospital, 61 Mizusawaryuugababa, Oshu, Iwate, 023-0864, Japan
| | - Reiichi Murakami
- Department of Cardiology and Nephrology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Hirofumi Tomita
- Department of Cardiology and Nephrology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Hisao Saitoh
- Department of Urology, Oyokyo Kidney Research Institute, 90 Kozawa Yamazaki, Hirosaki, Aomori, 036-8243, Japan
| | - Norihiko Tsuchiya
- Department of Urology, Yamagata University School of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9885, Japan
| | - Tomonori Habuchi
- Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan
| | - Wataru Obara
- Department of Urology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Morioka, Iwate, 028-3694, Japan
| | - Chikara Ohyama
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
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7
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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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8
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Jeon JY, Han-Bit S, Park BH, Lee N, Kim HJ, Kim DJ, Lee KW, Han SJ. Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients. Endocrinol Metab (Seoul) 2023; 38:139-145. [PMID: 36746391 PMCID: PMC10008662 DOI: 10.3803/enm.2022.1594] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 01/09/2023] [Indexed: 02/08/2023] Open
Abstract
BACKGRUOUND Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients. METHODS We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE. CONCLUSION Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.
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Affiliation(s)
- Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - Shin Han-Bit
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Bum Hee Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
- Office of Biostatistics, Medical Research Collaboration Center, Ajou Research Institute for Innovation, Ajou University Medical Center, Suwon, Korea
| | - Nami Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - Kwan-Woo Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
- Corresponding author: Seung Jin Han. Department of Endocrinology and Metabolism, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: +82-31-219-5126, Fax: +82-31-219-4497, E-mail:
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9
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Mota-Zamorano S, González LM, Robles NR, Valdivielso JM, Arévalo-Lorido JC, López-Gómez J, Gervasini G. Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy. Ann Med 2022; 54:3039-3051. [PMID: 36314849 PMCID: PMC9635471 DOI: 10.1080/07853890.2022.2138531] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/20/2022] [Accepted: 10/17/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) has become the major cause of end-stage kidney disease and is associated to an extremely high cardiovascular (CV) risk. METHODS We screened 318 DN patients for 23 SNPs in four glucose transporters (SLC2A1, SLC2A2, SLC5A1 and SLC5A2) and in KCNJ11 and ABCC8, which participate in insulin secretion. Regression models were utilised to identify associations with renal parameters, atherosclerosis measurements and CV events. In addition, 506 individuals with normal renal function were also genotyped as a control group. RESULTS In the patient's cohort, common carotid intima media thickness values were higher in carriers of ABCC8 rs3758953 and rs2188966 vs. non-carriers [0.78(0.25) vs. 0.72(0.22) mm, p < 0.05 and 0.79(0.26) vs. 0.72(0.22) mm, p < 0.05], respectively. Furthermore, ABCC8 rs1799859 was linked to presence of plaque in these patients [1.89(1.03-3.46), p < 0.05]. Two variants, SLC2A2 rs8192675 and SLC5A2 rs9924771, were associated with better [OR = 0.49 (0.30-0.81), p < 0.01] and worse [OR = 1.92 (1.15-3.21), p < 0.05] CV event-free survival, respectively. With regard to renal variables, rs841848 and rs710218 in SLC2A1, as well as rs3813008 in SLC5A2, significantly altered estimated glomerular filtration rate values [carriers vs. non-carriers: 30.41(22.57) vs. 28.25(20.10), p < 0.05; 28.95(21.11) vs. 29.52(21.66), p < 0.05 and 32.03(18.06) vs. 28.14(23.06) ml/min/1.73 m2, p < 0.05]. In addition, ABCC8 rs3758947 was associated with higher albumin-to-creatinine ratios [193.5(1139.91) vs. 160(652.90) mg/g, p < 0.05]. The epistasis analysis of SNP-pairs interactions showed that ABCC8 rs3758947 interacted with several SNPs in SLC2A2 to significantly affect CV events (p < 0.01). No SNPs were associated with DN risk. CONCLUSIONS Polymorphisms in genes determining glucose homeostasis may play a relevant role in renal parameters and CV-related outcomes of DN patients.
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Affiliation(s)
- Sonia Mota-Zamorano
- Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, Spain
- RICORS2040 Renal Research Network, Madrid, Spain
| | - Luz M. González
- Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, Spain
| | - Nicolás R. Robles
- RICORS2040 Renal Research Network, Madrid, Spain
- Service of Nephrology, Badajoz University Hospital, Badajoz, Spain
| | - José M. Valdivielso
- RICORS2040 Renal Research Network, Madrid, Spain
- Vascular and Renal Translational Research Group, UDETMA, IRBLleida, Lleida, Spain
| | | | - Juan López-Gómez
- Service of Clinical Analyses, Badajoz University Hospital, Badajoz, Spain
| | - Guillermo Gervasini
- Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, Badajoz, Spain
- RICORS2040 Renal Research Network, Madrid, Spain
- Institute of Biomarkers of Molecular and Metabolic Pathologies, Universidad de Extremadura, Badajoz, Spain
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10
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Bredewold OW, Chan J, Svensson M, Bruchfeld A, de Fijter JW, Furuland H, Grinyo JM, Hartmann A, Holdaas H, Hellberg O, Jardine A, Mjörnstedt L, Skov K, Smerud KT, Soveri I, Sørensen SS, Zonneveld AJV, Fellström B. Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: A Randomized Clinical Trial. Kidney Med 2022; 5:100574. [PMID: 36593877 PMCID: PMC9803830 DOI: 10.1016/j.xkme.2022.100574] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Rationale & Objective In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs. Study Design Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial. Setting & Participants KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion. Intervention Continuation with a CNI-based regimen or switch to belatacept for 12 months. Outcomes Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness. Results Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss. Limitations The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year. Conclusions We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate. Funding The trial has received a financial grant from Bristol-Myers Squibb. Trial Registration EudraCT no. 2013-001178-20.
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Affiliation(s)
- Obbo W. Bredewold
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands,Address for Correspondence: Obbo W. Bredewold, MD, Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Joe Chan
- Department of Renal Medicine, Akershus University Hospital, Lørenskog, Norway
| | - My Svensson
- Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark
| | - Annette Bruchfeld
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden,Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden
| | - Johan W. de Fijter
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Hans Furuland
- Department of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden
| | - Josep M. Grinyo
- Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Anders Hartmann
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Hallvard Holdaas
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Olof Hellberg
- Department of Internal Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Alan Jardine
- Department of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Lars Mjörnstedt
- Division of Transplantation, Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden
| | - Karin Skov
- Department of Renal Medicine, Aarhus University Hospital, Denmark
| | | | - Inga Soveri
- Department of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden
| | - Søren S. Sørensen
- Department of Nephrology, Copenhagen University Hospital, Copenhagen, Denmark
| | | | - Bengt Fellström
- Department of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden
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11
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Ribeiro PAB, Gradassi M, Martin SM, Leenknegt J, Baudet M, Le V, Pomey MP, Räkel A, Tournoux F. Clinical Implementation of Different Strategies for Exercise-Based Rehabilitation in Kidney and Liver Transplant Recipients: A Pilot Study. Arq Bras Cardiol 2022; 119:246-254. [PMID: 35946686 PMCID: PMC9363074 DOI: 10.36660/abc.20210159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 11/10/2021] [Indexed: 12/17/2022] Open
Abstract
Fundamento: A doença cardiovascular está entre as principais causas de morte entre pacientes transplantados. Embora esses pacientes possam teoricamente se beneficiar de programas de reabilitação baseada em exercícios (RBE), sua implementação ainda é um desafio. Objetivo: Apresentamos nossa experiência inicial em diferentes modos de realização de um programa piloto de RBE em receptores de transplante de rim e fígado. Métodos: Trinta e dois pacientes transplantados renais ou hepáticos foram convidados para um programa de RBE de 6 meses realizado na academia do hospital, na academia comunitária ou em casa, de acordo com a preferência do paciente. O nível de significância adotado foi de 5%. Resultados: Dez pacientes (31%) não completaram o programa. Entre os 22 que completaram, 7 treinaram na academia do hospital, 7 na academia comunitária e 8 em casa. O efeito geral foi um aumento de 11,4% nos METs máximos (tamanho do efeito de Hedges g = 0,39). O grupo de academia hospitalar teve um aumento nos METs de 25,5% (g = 0,58, tamanho de efeito médio) versus 10% (g = 0,25) e 6,5% (g = 0,20) para os grupos de academia comunitária e em casa, respectivamente. Houve efeito benéfico nas pressões arteriais sistólica e diastólica, maior para os grupos academia hospitalar (g= 0,51 e 0,40) e academia comunitária (g= 0,60 e 1,15) do que para os pacientes treinando em casa (g= 0,07 e 0,10). Nenhum evento adverso significativo foi relatado durante o seguimento. Conclusão: Programas de RBE em receptores de transplante de rim e fígado devem ser incentivados, mesmo que sejam realizados fora da academia do hospital, pois são seguros com efeitos positivos na capacidade de exercício e nos fatores de risco cardiovascular.
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Affiliation(s)
- Paula A B Ribeiro
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá
| | - Mathieu Gradassi
- Centre de Cardiologie Preventive du Centre Hospitalier de l'Université de Montréal, Quebec - Canadá
| | - Sarah-Maude Martin
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá.,Département des sciences de l'activité physique, Université du Québec à Montréal, Québec - Canadá
| | - Jonathan Leenknegt
- Centre de Cardiologie Preventive du Centre Hospitalier de l'Université de Montréal, Quebec - Canadá
| | - Mathilde Baudet
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá
| | - VyVan Le
- Centre de Cardiologie Preventive du Centre Hospitalier de l'Université de Montréal, Quebec - Canadá.,Département de Cardiologie du Centre Hospitalier de l'Université de Montréal, Québec - Canadá
| | - Marie-Pascale Pomey
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá.,École de santé publique, Université de Montréal, Québec - Canadá
| | - Agnes Räkel
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá.,Département d'Encrinologie du Centre Hospitalier de l'Université de Montréal, Québec - Canadá
| | - François Tournoux
- Unité de recherche @coeurlab - Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Quebec - Canadá.,Département de Cardiologie du Centre Hospitalier de l'Université de Montréal, Québec - Canadá
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12
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Babakry S, Rijkse E, Roodnat JI, Bijdevaate DC, IJzermans JNM, Minnee RC. Risk of post-transplant cardiovascular events in kidney transplant recipients with preexisting aortoiliac stenosis. Clin Transplant 2021; 36:e14515. [PMID: 34674329 PMCID: PMC9285727 DOI: 10.1111/ctr.14515] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 11/28/2022]
Abstract
Prediction of the risk of cardiovascular events (CVE's) is important to optimize outcomes after kidney transplantation. Aortoiliac stenosis is frequently observed during pre‐transplant screening. We hypothesized that these patients are at higher risk of post‐transplant CVE's due to the joint underlying atherosclerotic disease. Therefore, we aimed to assess whether aortoiliac stenosis was associated with post‐transplant CVE's. This retrospective, single‐center cohort study included adult kidney transplant recipients, transplanted between 2000 and 2016, with contrast‐enhanced imaging available. Aortoiliac stenosis was classified according to the Trans‐Atlantic Inter‐Society Consensus (TASC) II classification and was defined as significant in case of ≥50% lumen narrowing. The primary outcome was CVE‐free survival. Eighty‐nine of 367 patients had significant aortoiliac stenosis and were found to have worse CVE‐free survival (median CVE‐free survival: stenosis 4.5 years (95% confidence interval (CI) 2.8–6.2), controls 8.9 years (95% CI 6.8–11.0); log‐rank test P < .001). TASC II C and D lesions were independent risk factors for a post‐transplant CVE with a hazard ratio of 2.15 (95% CI 1.05–4.38) and 6.56 (95% CI 2.74–15.70), respectively. Thus, kidney transplant recipients with TASC II C and D aortoiliac stenosis require extensive cardiovascular risk management pre‐, peri,‐ and post‐transplantation.
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Affiliation(s)
- Shabnam Babakry
- Erasmus MC Transplant Institute, Division HPB and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Elsaline Rijkse
- Erasmus MC Transplant Institute, Division HPB and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Joke I Roodnat
- Erasmus MC Transplant Institute, Division of Nephrology, Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Diederik C Bijdevaate
- Department of Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Jan N M IJzermans
- Erasmus MC Transplant Institute, Division HPB and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Robert C Minnee
- Erasmus MC Transplant Institute, Division HPB and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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13
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Rambabova-Bushljetik I, Metzger J, Siwy J, Dohcev S, Bushljetikj O, Filipce V, Trajceska L, Mischak H, Spasovski G. Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients. Nephrol Dial Transplant 2021; 37:2014-2021. [PMID: 34634117 DOI: 10.1093/ndt/gfab297] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Kidney transplantation is the best treatment option for end stage kidney disease but is still associated with long term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of eGFR with irreversible graft changes. METHODS Fifty-two living donor kidney transplant recipients (KTR) with 8-years follow up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24h proteinuria. Graft function was estimated according to Nankivell. Urine samples at month 24 were analyzed by CE-MS followed by classification with the chronic kidney disease classifier CKD273. RESULTS CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = -0.29, P = 0.05). Receiver operating characteristics analysis for graft loss and death within the next six years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273 positive and negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. CONCLUSIONS Using a representative KTR cohort with 8-years follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as prognostic tool for long-term graft function risk stratification by large prospective clinical trials.
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Affiliation(s)
- Irena Rambabova-Bushljetik
- University Department of Nephrology, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
| | | | | | - Saso Dohcev
- University Department of Urology, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
| | - Oliver Bushljetikj
- University Department of Cardiology, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
| | - Venko Filipce
- University Department of Neurosurgery, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
| | - Lada Trajceska
- University Department of Nephrology, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
| | | | - Goce Spasovski
- University Department of Nephrology, Clinical Centre "Mother Theresa", Un. Sts Cyril and Methodius, Skopje, N. Macedonia
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14
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Detection of pro angiogenic and inflammatory biomarkers in patients with CKD. Sci Rep 2021; 11:8786. [PMID: 33888746 PMCID: PMC8062467 DOI: 10.1038/s41598-021-87710-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 03/30/2021] [Indexed: 11/08/2022] Open
Abstract
Cardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney disease (CKD). To identify new biomarkers of vascular injury and inflammation, we analyzed the proteome of plasma and circulating extracellular vesicles (EVs) in native and post-transplant CKD patients utilizing an aptamer-based assay. Proteins of angiogenesis were significantly higher in native and post-transplant CKD patients versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, and transforming growth factor-β as the top pathways activated in both CKD groups. Pro-inflammatory proteins were significantly higher only in the EVs of native CKD patients. IPA indicated acute phase response signaling, insulin-like growth factor-1, tumor necrosis factor-α, and interleukin-6 pathway activation. These data indicate that pathways of angiogenesis and inflammation are activated in CKD patients' plasma and EVs, respectively. The pathways common in both native and post-transplant CKD may signal similar mechanisms of CVD.
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15
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Deeb M, Gupta N, Overgaard CB, Li Y, Famure O, Joseph Kim S. Early postoperative acute myocardial infarction in kidney transplant recipients: A nested case-control study. Clin Transplant 2021; 35:e14283. [PMID: 33705576 DOI: 10.1111/ctr.14283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 02/22/2021] [Accepted: 02/24/2021] [Indexed: 11/26/2022]
Abstract
INTRODUCTION The epidemiology of early acute myocardial infarctions after kidney transplantation has not been well characterized. This study sought to examine the incidence, risk factors, and clinical outcomes of early acute myocardial infarctions or EAMI in kidney transplant recipients. METHODS A total of 1976 patients who underwent kidney transplantation at our center from Jan 1, 2000, to Sept 30, 2016, were included. A nested case-control design was used to study EAMI risk factors using a conditional logistic regression model. A Cox proportional hazards model was used to assess the association of EAMI with death-censored graft failure, death with graft function, and total graft failure. RESULTS Seventy four patients had an EAMI within 3 months post-transplant. Based on univariable analyses, risk factors for EAMI included age and recipient history of diabetes mellitus or coronary artery disease. After adjustment, recipient history of coronary artery disease was the only independent predictor for EAMI (OR 3.76, p < .001). Patients who experienced EAMI were more likely to experience death-censored graft failure, death with graft function, and total graft failure. CONCLUSION While the incidence of EAMI in kidney transplant recipients is relatively low, these data show that EAMI has profound long-term effects on morbidity and mortality.
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Affiliation(s)
- Maya Deeb
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Nikita Gupta
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Christopher B Overgaard
- Division of Cardiology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada
| | - Yanhong Li
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Olusegun Famure
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - S Joseph Kim
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada.,Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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16
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Infante B, Bellanti F, Correale M, Pontrelli P, Franzin R, Leo S, Calvaruso M, Mercuri S, Netti GS, Ranieri E, Brunetti ND, Grandaliano G, Gesualdo L, Serviddio G, Castellano G, Stallone G. mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction. Aging (Albany NY) 2021; 13:8026-8039. [PMID: 33758105 PMCID: PMC8034974 DOI: 10.18632/aging.202863] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 03/03/2021] [Indexed: 02/05/2023]
Abstract
CVD remains the major cause of mortality with graft functioning in Kidney transplant recipients (KTRs), with an estimated risk of CV events about 50-fold higher than in the general population. Many strategies have been considered to reduce the CV risk such as the use of mTOR inhibitors. We evaluate whether chronic mTOR inhibition might influence CV aging in KTRs studying the molecular mechanisms involved in this effect. We retrospectively analyzed 210 KTRs with stable graft function on therapy with CNI and mycophenolic acid (Group A, 105 pts.), or with CNI and mTORi (Everolimus, Group B, 105 pts.). The presence of mTOR inhibitor in immunosuppressive therapy was associated to increase serum levels of Klotho with concomitant reduction in FGF-23, with a significant decrease in left ventricular mass. In addition, KTRs with mTORi improved mitochondrial function/biogenesis in PBMC with more efficient oxidative phosphorylation, antioxidant capacity and glutathione peroxidase activity. Finally, group B KTRs presented reduced levels of inflammaging markers such as reduced serum pentraxin-3 and p21ink expression in PBMC. In conclusion, we demonstrated that mTOR inhibition in immunosuppressive protocols prevents the occurrence and signs of CV aging in KTRs.
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Affiliation(s)
- Barbara Infante
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Francesco Bellanti
- C.U.R.E. (University Center for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, Italy
| | - Michele Correale
- Cardiology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Paola Pontrelli
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy
| | - Rossana Franzin
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy
| | - Serena Leo
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Martina Calvaruso
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Silvia Mercuri
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Giuseppe Stefano Netti
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Elena Ranieri
- Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Natale Daniele Brunetti
- Cardiology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Giuseppe Grandaliano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy
| | - Gaetano Serviddio
- C.U.R.E. (University Center for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, Italy
| | - Giuseppe Castellano
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Giovanni Stallone
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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17
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Karabulut U, Keskin K. Does short-term dialysis significantly increase coronary artery disease burden in diabetic patients who undergo renal transplantation? INTERNATIONAL JOURNAL OF THE CARDIOVASCULAR ACADEMY 2021. [DOI: 10.4103/ijca.ijca_17_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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18
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Kim DG, Lee J, Seo WJ, Lee JG, Kim BS, Kim MS, Kim SI, Kim YS, Huh KH. Rituximab protects against development of atherosclerotic cardiovascular disease after kidney transplantation: a propensity-matched study. Sci Rep 2019; 9:16475. [PMID: 31712593 PMCID: PMC6848081 DOI: 10.1038/s41598-019-52942-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 10/25/2019] [Indexed: 12/17/2022] Open
Abstract
Recent studies have implicated B cells in atherosclerosis and have verified the atheroprotective effect of rituximab. Rituximab is widely used for desensitization in ABO-incompatible or crossmatch-positive kidney transplantation (KT). Using a single-center KT database, we performed propensity-matched analysis to investigate the association between rituximab and posttransplant atherosclerotic cardiovascular disease (ASCVD). Among 1299 eligible patients, 239 given rituximab induction were matched with 401 controls in a 1:2 propensity score matching process. The cumulative rate of ASCVD during 8 years of follow-up was significantly lower in rituximab-treated patients, compared with matched controls (3.7% vs. 11.2%; P = 0.012). However, all-cause mortality did not differ by group (2.9% vs. 4%; P = 0.943). In multivariable Cox analysis, rituximab proved independently protective of ASCVD (hazard ratio = 0.34, 95% confidence interval: 0.14–0.83). The lower risk of ASCVD seen with rituximab induction reached significance only in patient subsets of diabetes mellitus, pretransplant dialysis, or older age (>50 years). Rituximab induction confers a lower risk of ASCVD during the posttransplant period. This atheroprotective effect appears particularly beneficial in patients whose risk of ASCVD is heightened.
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Affiliation(s)
- Deok Gie Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Won Jun Seo
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Seok Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. .,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
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19
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Wilson RS, Lin T, Chambers CE, Kadry Z, Jain AB. Assessing cardiovascular risk in the prerenal transplant population: Comparison of myocardial perfusion imaging and coronary angiography with risk factor stratification. Clin Transplant 2019; 33:e13735. [PMID: 31628673 DOI: 10.1111/ctr.13735] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Patients with end-stage renal disease (ESRD) have a higher incidence of coronary artery disease (CAD). Hence, it is crucial to evaluate CAD before renal transplantation. This study compares the utility of pharmacologic single-photon emission computed-tomography (SPECT) imaging directly to coronary angiography for diagnosis of CAD with correlation to cardiovascular risk factors. METHOD Retrospective review of asymptomatic renal failure patients who underwent both SPECT and coronary angiography to identify obstructive CAD between the years 2008-2016. Ninety-four ESRD subjects were evaluated. RESULTS Myocardial perfusion SPECT study found, when compared to coronary angiography demonstrated for CAD, the sensitivity of 93.3% with a specificity of 73.4%. Importantly, the negative predictive value for coronary artery disease was 96%. With seven or more cardiac risk factors, 66.7% of patients had obstructive coronary artery disease. Among all the risk factors examined, patients with a previous history of coronary artery disease had a 68% risk of obstructive coronary artery disease. CONCLUSION Comparing myocardial perfusion imaging SPECT findings with coronary angiography in patients with ESRD, a sensitivity of 93.3% and a specificity of 73% were observed. Of all the risk factors examined, patient with the previous history of CAD was the single most significant risk factor for CAD in 68% of cases.
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Affiliation(s)
- Ryan S Wilson
- Heart and Vascular Institute, Division of Cardiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Tony Lin
- College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania
| | - Charles E Chambers
- Heart and Vascular Institute, Division of Cardiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Zakiyah Kadry
- Department of Surgery, Division of Transplant Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Ashokkumar B Jain
- Department of Surgery, Division of Transplant Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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20
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Neuberger J, Armstrong MJ, Fisher J, Mark P, Schmidtke K, Sharif A, Vlaev I. Sport and Exercise in Improving Outcomes After Solid Organ Transplantation: Overview From a UK Meeting. Transplantation 2019; 103:S1-S11. [PMID: 31259878 DOI: 10.1097/tp.0000000000002710] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Outcomes after solid organ transplantation continue to improve, but premature loss of life remains a major concern, with death from cerebrovascular disease and cardiovascular disease accounting for around 20% late deaths. There are multiple contributory factors including preexisting, and the posttransplant development of, cardiometabolic conditions (such as hypertension, diabetes mellitus, hyperlipidemia, and obesity). There is accumulating evidence that the regular engagement in exercise is an important factor affecting outcomes before, during, and after transplantation; yet most waitlist candidates and recipients have reduced levels of physical activity. The mechanisms whereby physical activity is associated with better outcomes and a reduction in risk factors for cardiovascular disease are incompletely understood. Attempts to increase physical activity in the transplant population, as in the general population, have had limited success. Use of concepts from Nudge theory provides an evidence-based approach that may help increase physical activity and so reduce premature mortality. Both National and International Transplant Games provide a vehicle for increasing physical activity in this population and may also help to reduce premature death by providing a forum for mutual support for recipients and their families as well as an excellent forum for highlighting the success and impact of organ donation.
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Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Matthew J Armstrong
- NIHR Biomedical Research Centre, University of Birmingham, Birmingham, United Kingdom
| | - James Fisher
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Patrick Mark
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Kelly Schmidtke
- Warwick Business School, University of Warwick, Coventry, United Kingdom
| | - Adnan Sharif
- Renal Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Ivo Vlaev
- Warwick Business School, University of Warwick, Coventry, United Kingdom
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21
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Pihlstrøm HK, Mjøen G, Mucha S, Franke A, Jardine A, Fellström B, Dahle DO, Holdaas H, Melum E. Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients. Am J Transplant 2019; 19:1444-1451. [PMID: 30457209 DOI: 10.1111/ajt.15191] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/27/2018] [Accepted: 11/08/2018] [Indexed: 01/25/2023]
Abstract
There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible.
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Affiliation(s)
- Hege K Pihlstrøm
- Section of Nephrology, Division of Surgery, Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Geir Mjøen
- Section of Nephrology, Division of Surgery, Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Sören Mucha
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, University Hospital Schleswig Holstein, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, University Hospital Schleswig Holstein, Kiel, Germany
| | - Alan Jardine
- British Heart Foundation, Glasgow Cardiovascular Research Centre, Glasgow, UK
| | - Bengt Fellström
- Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden
| | - Dag Olav Dahle
- Section of Nephrology, Division of Surgery, Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Hallvard Holdaas
- Section of Nephrology, Division of Surgery, Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Espen Melum
- Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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22
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Paoletti E, Citterio F, Corsini A, Potena L, Rigotti P, Sandrini S, Bussalino E, Stallone G. Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review. J Nephrol 2019; 33:69-82. [DOI: 10.1007/s40620-019-00609-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 04/05/2019] [Indexed: 12/20/2022]
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23
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Hall PS, Mitchell ED, Smith AF, Cairns DA, Messenger M, Hutchinson M, Wright J, Vinall-Collier K, Corps C, Hamilton P, Meads D, Lewington A. The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation. Health Technol Assess 2019; 22:1-274. [PMID: 29862965 DOI: 10.3310/hta22320] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. OBJECTIVES To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. DATA SOURCES We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. REVIEW METHODS The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. RESULTS The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. LIMITATIONS The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. CONCLUSIONS Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. STUDY REGISTRATION The systematic review within this study is registered as PROSPERO CRD42014013919. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Peter S Hall
- Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
| | | | - Alison F Smith
- Academy of Primary Care, Hull York Medical School, Hull, UK.,National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | - David A Cairns
- Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Michael Messenger
- National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | | | - Judy Wright
- Academy of Primary Care, Hull York Medical School, Hull, UK
| | | | | | - Patrick Hamilton
- Manchester Institute of Nephrology and Transplantation, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - David Meads
- Academy of Primary Care, Hull York Medical School, Hull, UK
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24
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Sandal S, Bae S, McAdams-DeMarco M, Massie AB, Lentine KL, Cantarovich M, Segev DL. Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation. Am J Transplant 2019; 19:1150-1159. [PMID: 30372596 PMCID: PMC6433494 DOI: 10.1111/ajt.15148] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/30/2018] [Accepted: 10/19/2018] [Indexed: 01/25/2023]
Abstract
Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell-depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all-cause mortality, CVE-related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL-2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92-1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89-1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00-1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all-cause or CVE-related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.
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Affiliation(s)
- Shaifali Sandal
- Department of Medicine, Divisions of Nephrology and Multi-Organ Transplant Program, McGill University Health Centre, Montreal, QC
| | - Sunjae Bae
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mara McAdams-DeMarco
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Allan B. Massie
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Krista L. Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA
| | - Marcelo Cantarovich
- Department of Medicine, Divisions of Nephrology and Multi-Organ Transplant Program, McGill University Health Centre, Montreal, QC
| | - Dorry L. Segev
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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25
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Doukky R, Fughhi I, Campagnoli T, Wassouf M, Kharouta M, Vij A, Anokwute C, Appis A, Ali A. Validation of a clinical pathway to assess asymptomatic renal transplant candidates using myocardial perfusion imaging. J Nucl Cardiol 2018; 25:2058-2068. [PMID: 28484986 DOI: 10.1007/s12350-017-0901-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 04/06/2017] [Indexed: 11/24/2022]
Abstract
BACKGROUND An AHA/ACCF scientific statement proposed 8 risk factors to assess the need for noninvasive coronary artery disease (CAD) surveillance in asymptomatic patients undergoing evaluation for kidney transplantation. The clinical application of these risk factors and the role of noninvasive testing in this context have not been defined. METHODS AND RESULTS We retrospectively followed a cohort of 581 consecutive kidney transplant recipients of whom 401 had pre-transplant radionuclide myocardial perfusion imaging (MPI) and 90 had pre-transplant coronary angiography. The sum of pre-transplant AHA/ACCF risk factors (age >60 years, hypertension, diabetes, cardiovascular disease, dyslipidemia, smoking, dialysis >1 year, left ventricular hypertrophy) was calculated. MPI scans were analyzed by a "blinded" reader. Patients were followed for a mean of 3.7 ± 2.3 years post-transplant for major adverse cardiac events (MACE), defined as cardiac death or non-fatal myocardial infarction. The sum of risk factors was associated with modest discriminatory capacity for obstructive angiographic CAD (area under the curve [AUC], 0.70; P = 0.004), 30-day post-operative MACE (AUC, 0.60; P = 0.036), and long-term MACE (AUC, 0.63; P < 0.001). A threshold of ≥3 risk factors was optimal for identifying patients at risk. MPI provided incremental predictive value for obstructive CAD (P = 0.02) and long-term MACE (P = 0.04) but not post-operative MACE (P = 0.56). MPI was best predictive of long-term MACE in intermediate risk (3-4 risk factors) patients. CONCLUSIONS Asymptomatic kidney transplant candidates with ≥3 AHA/ACCF risk factors are at increased cardiac risk, and should be considered for noninvasive CAD surveillance. Intermediate risk patients (3-4 factors) benefit the most from pre-transplant MPI to define long-term MACE risk.
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Affiliation(s)
- Rami Doukky
- Division of Cardiology, Cook County Health and Hospitals System, Chicago, IL, USA.
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA.
- Department of Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA.
- Division of Cardiology, John H. Stroger, Jr. Hospital of Cook County, 1901 W. Harrison Street, Chicago, IL, 60612, USA.
| | - Ibtihaj Fughhi
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
| | - Tania Campagnoli
- Division of Cardiology, Cook County Health and Hospitals System, Chicago, IL, USA
| | - Marwan Wassouf
- Department of Medicine, Fairview Hospital, Cleveland, OH, USA
| | - Michael Kharouta
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
| | - Aviral Vij
- Division of Cardiology, Cook County Health and Hospitals System, Chicago, IL, USA
| | - Chiedozie Anokwute
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
| | - Andrew Appis
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
| | - Amjad Ali
- Department of Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA
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26
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Pulse Pressure: A Risk Factor for Renal Transplant Failure or a Useful Therapeutic Target? Transplantation 2018; 103:662-663. [PMID: 30188414 DOI: 10.1097/tp.0000000000002441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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27
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Arbiol-Roca A, Padró-Miquel A, Vidal-Alabró A, Hueso M, Fontova P, Bestard O, Rama I, Torras J, Grinyó JM, Alía-Ramos P, Cruzado JM, Lloberas N. ANRIL as a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study. Transpl Int 2018; 31:1018-1027. [PMID: 29722077 DOI: 10.1111/tri.13276] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 12/18/2017] [Accepted: 04/20/2018] [Indexed: 01/09/2023]
Abstract
Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients. Several single-nucleotide polymorphisms (SNPs) in the ANRIL gene pathway have been associated with cardiovascular events (CE). The main objective was to ascertain whether ANRIL (rs10757278) and CARD8 (rs2043211) SNPs could mediate susceptibility to CE. This was an observational follow-up cohort study of renal transplant recipients at Bellvitge University Hospital (Barcelona) from 2000 to 2014. A total of 505 recipients were followed up until achievement of a CE. Patients who did not achieve the endpoint were followed up until graft loss, lost to follow-up or death. Survival analysis was used to ascertain association between genetic markers, clinical data, and outcome. Fifty-three patients suffered a CE after renal transplantation. Results showed a significant association between ANRIL SNP and CE. Homozygous GG for the risk allele showed higher risk for CE than A carriers for the protective allele [HR = 2.93(1.69-5.11), P < 0.0001]. This effect was maintained when it was analyzed in combination with CARD8, suggesting that CARD8 SNP could play a role in the ANRIL mechanism. However, our study does not clarify the molecular mechanism for the CARD8 SNP regulation by ANRIL. ANRIL SNP may predispose to the development of CE after successful kidney transplantation.
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Affiliation(s)
- Ariadna Arbiol-Roca
- Biochemistry Department, IDIBELL, Hospital Universitari de Bellvitge, Barcelona, Spain
- PhD student at Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Ariadna Padró-Miquel
- Biochemistry Department, IDIBELL, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Anna Vidal-Alabró
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Miquel Hueso
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Pere Fontova
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Oriol Bestard
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Ines Rama
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Joan Torras
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Josep M Grinyó
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Pedro Alía-Ramos
- Biochemistry Department, IDIBELL, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Josep Maria Cruzado
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Nuria Lloberas
- Nephrology and Transplantation group (2017 SGR189), Institut d'Investigació Biomèdica (IDIBELL), Hospital Universitari de Bellvitge, Barcelona, Spain
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28
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Stevens KK, Denby L, Patel RK, Mark PB, Kettlewell S, Smith GL, Clancy MJ, Delles C, Jardine AG. Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway. Nephrol Dial Transplant 2018; 32:1617-1627. [PMID: 27448672 PMCID: PMC5837731 DOI: 10.1093/ndt/gfw252] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 06/02/2016] [Indexed: 01/16/2023] Open
Abstract
Background Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects. Methods Resistance vessels from rats and humans (± CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flow-mediated dilatation. Results Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5-inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serum fibroblast growth factor 23. Conclusions These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD.
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Affiliation(s)
- Kathryn K Stevens
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.,The Renal Transplant Unit, Western Infirmary, (Now based at The Queen Elizabeth University Hospital) Glasgow, UK
| | - Laura Denby
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Rajan K Patel
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.,The Renal Transplant Unit, Western Infirmary, (Now based at The Queen Elizabeth University Hospital) Glasgow, UK
| | - Patrick B Mark
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.,The Renal Transplant Unit, Western Infirmary, (Now based at The Queen Elizabeth University Hospital) Glasgow, UK
| | - Sarah Kettlewell
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Godfrey L Smith
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Marc J Clancy
- The Renal Transplant Unit, Western Infirmary, (Now based at The Queen Elizabeth University Hospital) Glasgow, UK
| | - Christian Delles
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Alan G Jardine
- BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.,The Renal Transplant Unit, Western Infirmary, (Now based at The Queen Elizabeth University Hospital) Glasgow, UK
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Gervasini G, Luna E, Garcia-Pino G, Azevedo L, Mota-Zamorano S, José Cubero J. Polymorphisms in genes involved in vasoactive eicosanoid synthesis affect cardiovascular risk in renal transplant recipients. Curr Med Res Opin 2018; 34:247-253. [PMID: 29022765 DOI: 10.1080/03007995.2017.1391757] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients. METHODS In a cohort of 355 patients, we determined the presence of two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels. Associations with CV mortality, CV event-free long-term survival and graft survival were retrospectively investigated by logistic regression models. RESULTS CYP2J2*7 showed a statistical trend towards higher CV mortality (p = .06) and lower cardiac or cerebral event-free long-term survival (p = .05), whilst CYP2C8*3 displayed a significant inverse association with the risk of CV event (hazard ratio [HR] = 0.34 [0.15-0.78], p = .01). The association of CYP2J2*7 with CV mortality became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation (HR = 15.72 [2.83-91.94], p = .005). In this subgroup of patients both single nucleotide polymorphisms (SNPs) were significantly associated with event-free survival. HR values were 5.44 (1.60-18.51), p = .007 and 0.26 (0.09-0.75), p = .012 for CYP2J2*7 and CYP2C8*3, respectively. CONCLUSIONS Our results show, for the first time to our knowledge, that two SNPs in CYP2C8 and CYP2J2, which synthesize EETs, may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.
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Affiliation(s)
- Guillermo Gervasini
- a Department of Medical and Surgical Therapeutics, Division of Pharmacology , Medical School, University of Extremadura , Badajoz , Spain
| | - Enrique Luna
- b Service of Nephrology, Infanta Cristina University Hospital , Badajoz , Spain
| | - Guadalupe Garcia-Pino
- a Department of Medical and Surgical Therapeutics, Division of Pharmacology , Medical School, University of Extremadura , Badajoz , Spain
| | - Lilia Azevedo
- b Service of Nephrology, Infanta Cristina University Hospital , Badajoz , Spain
| | - Sonia Mota-Zamorano
- a Department of Medical and Surgical Therapeutics, Division of Pharmacology , Medical School, University of Extremadura , Badajoz , Spain
| | - Juan José Cubero
- b Service of Nephrology, Infanta Cristina University Hospital , Badajoz , Spain
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Early Prediction of Cardiovascular Disease in Kidney Transplant Recipients. Transplant Proc 2017; 49:2092-2098. [PMID: 29149967 DOI: 10.1016/j.transproceed.2017.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/02/2017] [Indexed: 12/31/2022]
Abstract
Cardiovascular disease (CVD) is frequent after kidney transplantation (KT). This study investigated CVD prediction in KT by information available before KT or within 6 months after KT. The study cohort consisted of 629 patients with KT in 2005-10 and with adult age at KT. The end point was incidence up to 2015 of CVD (coronary heart disease, cerebrovascular disease, peripheral artery disease). Graft failure, non-CVD death with functioning graft, and loss to follow-up were considered competing events. CVD prediction was investigated for 34 variables by means of competing-risks regression. Follow-up range was 0.28-10.00 years (mean ± SD, 7.30 ± 3.10). First incident event was CVD in 103 patients and competing events in 146 patients. In the multivariable model for pre-KT variables only, CVD predictors were male sex (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.06-2.66), diabetic nephropathy (HR, 6.63; 95% CI, 1.81-24.35), pre-KT dialysis for ≥5 years (HR, 1.52; 95% CI, 1.02-2.27), pre-KT CVD (HR, 4.87; 95% CI, 2.84-8.35), and age at KT ≥45 years (HR, 2.98; 95% CI, 1.83-4.87). In the model for pre-KT and post-KT variables together, the sole post-KT CVD predictor was estimated glomerular filtration rate <60 mL/min at the 6-month visit (HR, 1.75; 95% CI, 1.11-2.77). Diabetic nephropathy, pre-KT dialysis, pre-KT CVD, and age at KT predicted 91.2% of incident CVD. Early available information effectively predicted CVD in KT independently from competing events.
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31
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Ladhani M, Craig JC, Irving M, Clayton PA, Wong G. Obesity and the risk of cardiovascular and all-cause mortality in chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant 2017; 32:439-449. [PMID: 27190330 DOI: 10.1093/ndt/gfw075] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 03/12/2016] [Indexed: 01/18/2023] Open
Abstract
Background Obesity is a risk factor for cardiovascular disease and death in people without chronic kidney disease (CKD), but the effect of obesity in people with CKD is uncertain. Methods Medline and Embase (from inception to January 2015) were searched for cohort studies measuring obesity by body mass index (BMI), waist:hip ratio (WHR) and/or waist circumference (WC) and all-cause and cardiovascular mortality or events in patients with any stage of CKD. Data were summarized using random effects models. Meta-regression was conducted to assess sources of heterogeneity. Results Of 4065 potentially eligible citations, 165 studies ( n = 1 534 845 participants) were analyzed. In studies that found a nonlinear relationship, underweight people with CKD (3-5) on hemodialysis experienced an increased risk of death compared with those with normal weight. In transplant recipients, excess risk was observed at levels of morbid obesity (>35 kg/m 2 ). Of studies that found the relationship to be linear, a 1 kg/m 2 increase in BMI was associated with a 3 and 4% reduction in all-cause and cardiovascular mortality in patients on hemodialysis, respectively {adjusted hazard ratio [HR] 0.97 [95% confidence interval (CI) 0.96-0.98] and adjusted HR 0.96 (95% CI 0.92-1.00)}. In CKD Stages 3-5, for every 1 kg/m 2 increase in BMI there was a 1% reduction in all-cause mortality [HR 0.99 (95% CI 0.0.97-1.00)]. There was no apparent association between obesity and mortality in transplanted patients or those on peritoneal dialysis. Sparse data for WHR and WC did not allow further analyses. Conclusions Being obese may be protective for all-cause mortality in the predialysis and hemodialysis populations, while being underweight suggests increased risk, but not in transplant recipients.
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Affiliation(s)
- Maleeka Ladhani
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia.,Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
| | - Jonathan C Craig
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia.,Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
| | - Michelle Irving
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Philip A Clayton
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
| | - Germaine Wong
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia.,Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.,Centre for Renal and Transplant Research, Westmead Hospital, Westmead, NSW, Australia
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32
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Yilmaz KC, Akgün AN, Ciftci O, Muderrisoglu H, Sezer S, Moray G, Haberal M. Preoperative Cardiac Risk Assessment in Renal Transplant Recipients: A Single-Center Experience. EXP CLIN TRANSPLANT 2017; 17:478-482. [PMID: 29025386 DOI: 10.6002/ect.2017.0145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Cardiovascular disease is the major cause of morbidity and mortality in patients on renal replacement therapy and in kidney transplant recipients. There are no specific recommendations for preoperative cardiac risk assessment before renal transplant. The aim of our study was to analyze preoperative cardiac test frequencies, test results, patient characteristics, and relations between cardiac stress test results and severe coronary artery disease. MATERIALS AND METHODS We retrospectively examined patients who underwent renal transplant between December 2011 and December 2016 in our hospital (Ankara, Turkey). Our study group included 216 patients. All patients had preoperative echocardiography. We recorded results of exercise stress tests, myocardial perfusion scintigraphy, and coronary angiography. For all patients, preoperative complete blood cell count, creatinine, high-density lipoprotein, triglycerides, low-density lipoprotein, and red cell distribution width values were obtained and recorded. RESULTS We classified patient groups according to presence or absence of severe coronary artery disease. Fourteen of 66 patients had severe coronary artery disease. In univariate analyses, age, having a history of familial coronary artery disease, diabetes mellitus, presence of coronary artery disease, and triglyceride levels were risk factors for severe coronary artery disease. In multivariate analysis, diabetes mellitus, presence of coronary artery disease, and having a history of familial coronary artery disease were statistically significant. CONCLUSIONS Renal transplant recipients are a special patient population, and there must be specific suggestions for this population. If patients present with more than 1 risk factor, a stress test should be performed to evaluate cardiovascular risk. In some patients, especially those whose risk factors include prior cardiovascular disease or diabetes mellitus, stress tests should be skipped and patients should directly undergo coronary angiography to look for severe coronary artery disease.
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Affiliation(s)
- Kerem Can Yilmaz
- From the Cardiology Department, Baskent University Faculty of Medicine, Ankara, Turkey
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Foster M, Weiner D, Bostom A, Carpenter M, Inker L, Jarolim P, Joseph A, Kusek J, Pesavento T, Pfeffer M, Rao M, Solomon S, Levey A. Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial. Am J Transplant 2017; 17:2390-2399. [PMID: 28257169 PMCID: PMC5573607 DOI: 10.1111/ajt.14258] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 02/09/2017] [Accepted: 02/11/2017] [Indexed: 01/25/2023]
Abstract
Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFRcys ), B2M (eGFRB2M ), and creatinine (eGFRcr ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr , eGFRcys , and eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and eGFRB2M <30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr . We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.
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Affiliation(s)
- M.C. Foster
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - D.E. Weiner
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | | | - M.A. Carpenter
- Department of Biostatistics, University of North Carolina, Chapel Hill, NC
| | - L.A. Inker
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - P. Jarolim
- Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - A.A. Joseph
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - J.W. Kusek
- National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
| | - T. Pesavento
- The Ohio State University Medical Center, Columbus, OH
| | - M.A. Pfeffer
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - M. Rao
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - S.D. Solomon
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - A.S. Levey
- Division of Nephrology, Tufts Medical Center, Boston, MA
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Baker RJ, Mark PB, Patel RK, Stevens KK, Palmer N. Renal association clinical practice guideline in post-operative care in the kidney transplant recipient. BMC Nephrol 2017; 18:174. [PMID: 28571571 PMCID: PMC5455080 DOI: 10.1186/s12882-017-0553-2] [Citation(s) in RCA: 125] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 04/16/2017] [Indexed: 02/08/2023] Open
Abstract
These guidelines cover the care of patients from the period following kidney transplantation until the transplant is no longer working or the patient dies. During the early phase prevention of acute rejection and infection are the priority. After around 3-6 months, the priorities change to preservation of transplant function and avoiding the long-term complications of immunosuppressive medication (the medication used to suppress the immune system to prevent rejection). The topics discussed include organization of outpatient follow up, immunosuppressive medication, treatment of acute and chronic rejection, and prevention of complications. The potential complications discussed include heart disease, infection, cancer, bone disease and blood disorders. There is also a section on contraception and reproductive issues.Immediately after the introduction there is a statement of all the recommendations. These recommendations are written in a language that we think should be understandable by many patients, relatives, carers and other interested people. Consequently we have not reworded or restated them in this lay summary. They are graded 1 or 2 depending on the strength of the recommendation by the authors, and AD depending on the quality of the evidence that the recommendation is based on.
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Affiliation(s)
- Richard J Baker
- Renal Unit, St. James's University Hospital, Leeds, England.
| | - Patrick B Mark
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, Scotland
| | - Rajan K Patel
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, Scotland
| | - Kate K Stevens
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, Scotland
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Gao F, Yao YC, Cai SB, Zhao TR, Yang XY, Fan J, Li XN, Cao JX, Cheng GG. Novel immunosuppressive pregnane glycosides from the leaves of Epigynum auritum. Fitoterapia 2017; 118:107-111. [DOI: 10.1016/j.fitote.2017.02.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Revised: 02/10/2017] [Accepted: 02/12/2017] [Indexed: 10/20/2022]
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Seoane-Pillado MT, Pita-Fernández S, Valdés-Cañedo F, Seijo-Bestilleiro R, Pértega-Díaz S, Fernández-Rivera C, Alonso-Hernández Á, González-Martín C, Balboa-Barreiro V. Incidence of cardiovascular events and associated risk factors in kidney transplant patients: a competing risks survival analysis. BMC Cardiovasc Disord 2017; 17:72. [PMID: 28270107 PMCID: PMC5341360 DOI: 10.1186/s12872-017-0505-6] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 02/28/2017] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The high prevalence of cardiovascular risk factors among the renal transplant population accounts for increased mortality. The aim of this study is to determine the incidence of cardiovascular events and factors associated with cardiovascular events in these patients. METHODS An observational ambispective follow-up study of renal transplant recipients (n = 2029) in the health district of A Coruña (Spain) during the period 1981-2011 was completed. Competing risk survival analysis methods were applied to estimate the cumulative incidence of developing cardiovascular events over time and to identify which characteristics were associated with the risk of these events. Post-transplant cardiovascular events are defined as the presence of myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances, peripheral vascular disease and cardiovascular disease and death. The cause of death was identified through the medical history and death certificate using ICD9 (390-459, except: 427.5, 435, 446, 459.0). RESULTS The mean age of patients at the time of transplantation was 47.0 ± 14.2 years; 62% were male. 16.5% had suffered some cardiovascular disease prior to transplantation and 9.7% had suffered a cardiovascular event. The mean follow-up period for the patients with cardiovascular event was 3.5 ± 4.3 years. Applying competing risk methodology, it was observed that the accumulated incidence of the event was 5.0% one year after transplantation, 8.1% after five years, and 11.9% after ten years. After applying multivariate models, the variables with an independent effect for predicting cardiovascular events are: male sex, age of recipient, previous cardiovascular disorders, pre-transplant smoking and post-transplant diabetes. CONCLUSIONS This study makes it possible to determine in kidney transplant patients, taking into account competitive events, the incidence of post-transplant cardiovascular events and the risk factors of these events. Modifiable risk factors are identified, owing to which, changes in said factors would have a bearing of the incidence of events.
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Affiliation(s)
- María Teresa Seoane-Pillado
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Salvador Pita-Fernández
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | | | - Rocio Seijo-Bestilleiro
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Sonia Pértega-Díaz
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | | | | | - Cristina González-Martín
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Vanesa Balboa-Barreiro
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
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Lam NN, Kim SJ, Knoll GA, McArthur E, Lentine KL, Naylor KL, Li AH, Shariff SZ, Ribic CM, Garg AX. The Risk of Cardiovascular Disease Is Not Increasing Over Time Despite Aging and Higher Comorbidity Burden of Kidney Transplant Recipients. Transplantation 2017; 101:588-596. [DOI: 10.1097/tp.0000000000001155] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Anastasopoulos NA, Dounousi E, Papachristou E, Pappas C, Leontaridou E, Savvidaki E, Goumenos D, Mitsis M. Cardiovascular disease: Risk factors and applicability of a risk model in a Greek cohort of renal transplant recipients. World J Transplant 2017; 7:49-56. [PMID: 28280695 PMCID: PMC5324028 DOI: 10.5500/wjt.v7.i1.49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 11/17/2016] [Accepted: 01/03/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the incidence and the determinants of cardiovascular morbidity in Greek renal transplant recipients (RTRs) expressed as major advance cardiac event (MACE) rate.
METHODS Two hundred and forty-two adult patients with a functioning graft for at least three months and available data that were followed up on the August 31, 2015 at two transplant centers of Western Greece were included in this study. Baseline recipients’ data elements included demographics, clinical characteristics, history of comorbid conditions and laboratory parameters. Follow-up data regarding MACE occurrence were collected retrospectively from the patients’ records and MACE risk score was calculated for each patient.
RESULTS The mean age was 53 years (63.6% males) and 47 patients (19.4%) had a pre-existing cardiovascular disease (CVD) before transplantation. The mean estimated glomerular filtration rate was 52 ± 17 mL/min per 1.73 m2. During follow-up 36 patients (14.9%) suffered a MACE with a median time to MACE 5 years (interquartile range: 2.2-10 years). Recipients with a MACE compared to recipients without a MACE had a significantly higher mean age (59 years vs 52 years, P < 0.001) and a higher prevalence of pre-existing CVD (44.4% vs 15%, P < 0.001). The 7-year predicted mean risk for MACE was 14.6% ± 12.5% overall. In RTRs who experienced a MACE, the predicted risk was 22.3% ± 17.1% and was significantly higher than in RTRs without an event 13.3% ± 11.1% (P = 0.003). The discrimination ability of the model in the Greek database of RTRs was good with an area under the receiver operating characteristics curve of 0.68 (95%CI: 0.58-0.78).
CONCLUSION In this Greek cohort of RTRs, MACE occurred in 14.9% of the patients, pre-existing CVD was the main risk factor, while MACE risk model was proved a dependable utility in predicting CVD post RT.
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Abstract
BACKGROUND Morbid obesity has reached epidemic proportions in developed nations worldwide, causing considerable mortality and increased healthcare expenditures. The use of gastric bypass surgery to achieve weight loss in morbidly obese patients with chronic renal failure (CRF) and postrenal transplant patients has not been studied adequately. METHODS Forty-one patients with different stages of CRF (25 already receiving dialysis) underwent a gastric bypass (GBP), and an additional 10 patients underwent a GBP after becoming morbidly obese after transplantation. RESULTS Of the 41 patients with CRF, 5 stabilized or resolved their kidney disease and 9 underwent successful transplantation. These patients had a loss of 68% excess body mass index (BMI) by 12 months after GBP. Of the 10 patients with GBP after transplant, the mean loss of excess BMI was 70.5%. There were no in-hospital or 30-day mortalities, but 8 of the 51 patients died from 112 to 2869 days postoperatively, 7 from cardiac or vascular events and 1 from an automobile accident. This compares with an approximate 10% mortality per year for patients receiving dialysis. Comorbid conditions associated with morbid obesity improved in all patients and permitted eligibility for transplantation. CONCLUSIONS GBP for massive weight reduction in morbidly obese renal failure and transplant patients leads to a reduction in comorbid conditions that are associated with an increased risk for cardiovascular deaths. There was no operative mortality in this series, and all but 1 death were related to previously existing disease of the cardiovascular system.
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Affiliation(s)
- J Wesley Alexander
- Center for Surgical Weight Loss, University of Cincinnati, Cincinnati, OH 45219, USA.
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40
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Fabbian F, De Giorgi A, Manfredini F, Lamberti N, Forcellini S, Storari A, Todeschini P, Gallerani M, La Manna G, Mikhailidis DP, Manfredini R. Impact of comorbidity on outcome in kidney transplant recipients: a retrospective study in Italy. Intern Emerg Med 2016; 11:825-832. [PMID: 27003820 DOI: 10.1007/s11739-016-1438-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 03/09/2016] [Indexed: 01/06/2023]
Abstract
The aim of this study was to relate in-hospital mortality (IHM), cardiovascular events (CVEs) and non-immunologic comorbidity evaluated on the basis of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codification, in Italian kidney transplant recipients (KTRs). We evaluated IHM and admissions due to CVEs between 2000 and 2013 recorded in the database of the region Emilia Romagna. The Elixhauser score was calculated for evaluation of non-immunologic comorbidity. Three main outcomes (i.e. IHM, admission due to major CVEs and combined outcome) were the dependent variables of the multivariate models, while age, gender and Elixhauser score were the independent ones. During the examined period, a total of 9063 admissions in 3648 KTRs were recorded; 1945 patients were males (53.3 %) and 1703 females (46.7 %) and the mean age was 52.9 ± 13.1 years. The non-immunological impaired status of the KTRs, examined by the Elixhauser score, was 3.88 ± 4.29. During the 14-year follow-up period, IHM for any cause was 3.2 % (n = 117), and admissions due to CVEs were 527 (5.8 %). Age and comorbidity were independently associated with CVEs, IHM and the combined outcome. Male gender was independently associated with IHM and combined outcome, but not with CVEs. Evaluation of non-immunological comorbidity is important in KTRs and identification of high-risk patients for major clinical events could improve outcome. Moreover, comorbidity could be even more important in chronic kidney disease patients who are waiting for a kidney transplant.
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Affiliation(s)
- Fabio Fabbian
- Clinica Medica Unit, Department of Medical Sciences, School of Medicine, University of Ferrara, Via L. Ariosto 25, 44121, Ferrara, Italy.
| | - Alfredo De Giorgi
- Clinica Medica Unit, Department of Medical Sciences, School of Medicine, University of Ferrara, Via L. Ariosto 25, 44121, Ferrara, Italy
| | - Fabio Manfredini
- Department of Biomedical Sciences and Surgical Specialties, School of Medicine, University of Ferrara, Ferrara, Italy
| | - Nicola Lamberti
- Department of Biomedical Sciences and Surgical Specialties, School of Medicine, University of Ferrara, Ferrara, Italy
| | - Silvia Forcellini
- Nephrology Unit, Department of Specialistic Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Alda Storari
- Nephrology Unit, Department of Specialistic Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Paola Todeschini
- Department of Specialistic, Diagnostic and Experimental Medicine, School of Medicine, University of Bologna, Bologna, Italy
| | - Massimo Gallerani
- Department of Internal Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Gaetano La Manna
- Department of Specialistic, Diagnostic and Experimental Medicine, School of Medicine, University of Bologna, Bologna, Italy
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry (Vascular Disease Prevention Clinic), University College London (UCL) Medical School, London, UK
| | - Roberto Manfredini
- Clinica Medica Unit, Department of Medical Sciences, School of Medicine, University of Ferrara, Via L. Ariosto 25, 44121, Ferrara, Italy
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Inhibition of Histone Deacetylase 6 Reveals a Potent Immunosuppressant Effect in Models of Transplantation. Transplantation 2016; 100:1667-74. [DOI: 10.1097/tp.0000000000001208] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.
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Affiliation(s)
- Mrudula R Munagala
- Department of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Avenue, Suite # L4, Newark, NJ 07112, USA.
| | - Anita Phancao
- Integris Baptist Medical Center, 3400 Northwest Expressway, Building C, Suite 200, Oklahoma City, OK 73112, USA
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Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant 2015; 5:183-95. [PMID: 26722646 PMCID: PMC4689929 DOI: 10.5500/wjt.v5.i4.183] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 08/19/2015] [Accepted: 09/25/2015] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.
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Zhou J, Qin L, Yi T, Ali R, Li Q, Jiao Y, Li G, Tobiasova Z, Huang Y, Zhang J, Yun JJ, Sadeghi MM, Giordano FJ, Pober JS, Tellides G. Interferon-γ-mediated allograft rejection exacerbates cardiovascular disease of hyperlipidemic murine transplant recipients. Circ Res 2015; 117:943-55. [PMID: 26399469 DOI: 10.1161/circresaha.115.306932] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 09/23/2015] [Indexed: 01/05/2023]
Abstract
RATIONALE Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. OBJECTIVE To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. METHODS AND RESULTS We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. CONCLUSIONS Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.
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Affiliation(s)
- Jing Zhou
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.).
| | - Lingfeng Qin
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Tai Yi
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Rahmat Ali
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Qingle Li
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Yang Jiao
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Guangxin Li
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Zuzana Tobiasova
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Yan Huang
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Jiasheng Zhang
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - James J Yun
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Mehran M Sadeghi
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Frank J Giordano
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - Jordan S Pober
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.)
| | - George Tellides
- From the Departments of Surgery (J.Z., L.Q., R.A., Q.L., Y.J., G.L., J.J.Y., G.T.) and Immunobiology (T.Y., Z.T., J.S.P.) and Medicine (Y.H., J.Z., M.M.S., F.J.G.) and the Interdepartmental Program in Vascular Biology and Therapeutics (J.J.Y., M.M.S., F.J.G., J.S.P., G.T.), Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, West Haven (J.J.Y., M.M.S., F.J.G., G.T.); Research Institute, Nationwide Children's Hospital, Columbus, OH (T.Y.); and Department of Vascular Surgery, Peking University People's Hospital, Beijing, P.R. China (Q.L., Y.J.).
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Szabó RP, Varga I, Balla J, Zsom L, Nemes B. Cardiovascular Screening and Management Among Kidney Transplant Candidates in Hungary. Transplant Proc 2015; 47:2192-5. [PMID: 26361677 DOI: 10.1016/j.transproceed.2015.07.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. METHODS Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. RESULTS According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. CONCLUSION In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes.
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Affiliation(s)
- R P Szabó
- FMC Debrecen, Extracorporal Organsupport Centre, University of Debrecen, Debrecen, Hungary; Institute of Surgery, Division of Transplantation, University of Debrecen, Debrecen, Hungary.
| | - I Varga
- Institute of Cardiology, University of Debrecen, Debrecen, Hungary
| | - J Balla
- FMC Debrecen, Extracorporal Organsupport Centre, University of Debrecen, Debrecen, Hungary; 1st Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - L Zsom
- Institute of Surgery, Division of Transplantation, University of Debrecen, Debrecen, Hungary
| | - B Nemes
- Institute of Surgery, Division of Transplantation, University of Debrecen, Debrecen, Hungary
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Parikh K, Appis A, Doukky R. Cardiac imaging for the assessment of patients being evaluated for kidney or liver transplantation. J Nucl Cardiol 2015; 22:282-96. [PMID: 25294437 DOI: 10.1007/s12350-014-9997-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 09/10/2014] [Indexed: 01/13/2023]
Abstract
Cardiac risk assessment prior to kidney and liver transplantation is controversial. Given the paucity of available organs, selecting appropriate recipients with favorable short- and long-term cardiovascular risk profile is crucial. Using noninvasive cardiac imaging tools to guide cardiovascular risk assessment and management can also be challenging and controversial. In this article, we address the burden of coronary artery disease among kidney and liver transplant candidates and review the literature pertaining to the diagnostic accuracy and the prognostic value of noninvasive cardiac imaging techniques in this population.
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Affiliation(s)
- Kalindi Parikh
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
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Tomita Y, Iwadoh K, Kutsunai K, Koyama I, Nakajima I, Fuchinoue S. Negative impact of underlying non-insulin-dependent diabetes mellitus nephropathy on long-term allograft survival in kidney transplantation: a 10-year analysis from a single center. Transplant Proc 2014; 46:3438-42. [PMID: 25498068 DOI: 10.1016/j.transproceed.2014.04.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Accepted: 04/22/2014] [Indexed: 11/29/2022]
Abstract
INTRODUCTION We analyzed the relationship between underlying nephropathy and long-term outcomes in kidney transplant recipients. METHODS We retrospectively analyzed data from 678 patients who underwent kidney transplantation (KTx) between 1998 and 2011. Recipients with 13 major nephropathies were evaluated for graft and patient survival, and causes of graft loss. RESULTS The best 10-year graft survival rates (100%) were in the patients with autosomal-dominant polycystic kidney disease, preeclampsia, Alport syndrome, and purpura nephritis. The worst rate (50.8%) was in patients with non-insulin-dependent diabetes mellitus nephropathy (NIDDMN; P = .039). Causes of graft-loss in the NIDDM patients included chronic rejection (6 cases), acute rejection (3 cases), infection (2 cases), and cardiovascular event (2 cases). Significant risk factors for graft loss were donor age (P < .01) and NIDDMN (P < .01). CONCLUSION Underlying NIDDMN before KTx was a significant risk factor for long-term graft function. Immunologic factors and nonimmunologic factors influenced the long-term outcomes in patients with underlying NIDDMN.
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Affiliation(s)
- Y Tomita
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan.
| | - K Iwadoh
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan
| | - K Kutsunai
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan
| | - I Koyama
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan
| | - I Nakajima
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan
| | - S Fuchinoue
- Department of Surgery B, Tokyo Women's Medical University, Tokyo, Japan
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Sarnak MJ, Bloom R, Muntner P, Rahman M, Saland JM, Wilson PWF, Fried L. KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. Am J Kidney Dis 2014; 65:354-66. [PMID: 25465166 DOI: 10.1053/j.ajkd.2014.10.005] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 10/22/2014] [Indexed: 01/12/2023]
Abstract
The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guideline for management of dyslipidemia in chronic kidney disease (CKD) was published in 2003. Since then, considerable evidence, including randomized controlled trials of statin therapy in adults with CKD, has helped better define medical treatments for dyslipidemia. In light of the new evidence, KDIGO (Kidney Disease: Improving Global Outcomes) formed a work group for the management of dyslipidemia in patients with CKD. This work group developed a new guideline that contains substantial changes from the prior KDOQI guideline. KDIGO recommends treatment of dyslipidemia in patients with CKD primarily based on risk for coronary heart disease, which is driven in large part by age. The KDIGO guideline does not recommend using low-density lipoprotein cholesterol level as a guide for identifying individuals with CKD to be treated or as treatment targets. Initiation of statin treatment is no longer recommended in dialysis patients. To assist US practitioners in interpreting and applying the KDIGO guideline, NKF-KDOQI convened a work group to write a commentary on this guideline. For the most part, our work group agreed with the recommendations of the KDIGO guideline, although we describe several areas in which we believe the guideline statements are either too strong or need to be more nuanced, areas of uncertainty and inconsistency, as well as additional research recommendations. The target audience for the KDIGO guideline includes nephrologists, primary care practitioners, and non-nephrology specialists such as cardiologists and endocrinologists. As such, we also put the current recommendations into the context of other clinical practice recommendations for cholesterol treatment.
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Affiliation(s)
| | - Roy Bloom
- University of Pennsylvania, Philadelphia, PA
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Ikitimur B, Cosansu K, Karadag B, Cakmak HA, Avci BK, Erturk E, Seyahi N, Ongen Z. Long-Term Impact of Different Immunosuppressive Drugs on QT and PR Intervals in Renal Transplant Patients. Ann Noninvasive Electrocardiol 2014; 20:426-32. [PMID: 25367596 DOI: 10.1111/anec.12225] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Sudden cardiac deaths due to arrhythmias are thought to be an important cause of mortality in patients with renal transplants. Exposure to immunosuppressive drugs may lead to QT or PR interval abnormalities which may consequently cause arrhythmias. Our study investigated the long term impact of four different immunosuppressive drugs on PR and corrected QT intervals (QTc) in renal transplant patients METHODS The study population consisted of 98 kidney transplant recipients. Study patients were receiving immunosuppressive management with tacrolimus, cyclosporine A, everolimus or azathioprine according to the local protocols. QTc and PR intervals obtained from the most recent post-transplant electrocardiograms were compared with the pre-transplant intervals dated before the transplantation procedure. RESULTS Post-transplant QTc intervals had prolonged significantly in comparison to the pre-transplant QTc intervals in all groups. However, there were no significant differences between the immunosuppressive agents with regard to post-transplant QTc interval prolongation (p > 0.05). There were no significant differences between the groups with regard to the pre and post-transplant PR interval changes (p > 0.05). CONCLUSIONS QT interval prolongation, a marker of risk for arrhythmias and sudden death, is highly prevalent among kidney transplant patients receiving different classes of immunosuppressive drugs.
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Affiliation(s)
- Baris Ikitimur
- Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Bilgehan Karadag
- Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Burcak Kilickiran Avci
- Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
| | - Emre Erturk
- Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
| | - Nurhan Seyahi
- Department of Nephrology, , Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
| | - Zeki Ongen
- Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey
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Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int 2014; 28:10-21. [PMID: 25081992 DOI: 10.1111/tri.12413] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 07/28/2014] [Indexed: 12/14/2022]
Abstract
Kidney transplantation is the optimal treatment for patients with end stage renal disease (ESRD) who would otherwise require dialysis. Patients with ESRD are at dramatically increased cardiovascular (CV) risk compared with the general population. As well as improving quality of life, successful transplantation accords major benefits by reducing CV risk in these patients. Worldwide, cardiovascular disease remains the leading cause of death with a functioning graft and therefore is a leading cause of graft failure. This review focuses on the mechanisms underpinning excess CV morbidity and mortality and current evidence for improving CV risk in kidney transplant recipients. Conventional CV risk factors such as hypertension, diabetes mellitus, dyslipidaemia and pre-existing ischaemic heart disease are all highly prevalent in this group. In addition, kidney transplant recipients exhibit a number of risk factors associated with pre-existing renal disease. Furthermore, complications specific to transplantation may ensue including reduced graft function, side effects of immunosuppression and post-transplantation diabetes mellitus. Strategies to improve CV outcomes post-transplantation may include pharmacological intervention including lipid-lowering or antihypertensive therapy, optimization of graft function, lifestyle intervention and personalizing immunosuppression to the individual patients risk profile.
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