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Belal AA, Santos Jr AH, Kazory A, Koratala A. Providing care for kidney transplant recipients: An overview for generalists. World J Nephrol 2025; 14:99555. [DOI: 10.5527/wjn.v14.i1.99555] [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: 07/24/2024] [Revised: 12/25/2024] [Accepted: 01/02/2025] [Indexed: 01/20/2025] Open
Abstract
Kidney transplantation is the preferred treatment for patients with advanced chronic kidney disease and end-stage kidney disease, offering superior quality of life and survival compared to dialysis. This manuscript provides an updated overview of post-transplant care, highlighting recent advancements and current practices to assist generalists in managing these patients. It covers key areas such as immunosuppression strategies, drug interactions, and the management of transplant-specific acute kidney injury. The focus includes the use of sodium-glucose cotransporter-2 inhibitors and cell-free DNA monitoring for evaluating allograft health and immune-mediated injury. The manuscript reviews the fundamentals of immunosuppression, including both induction and maintenance therapies, and underscores the importance of monitoring kidney function, as well as addressing hypertension, diabetes, and infections. It also provides recommendations for vaccinations and cancer screening tailored to kidney transplant recipients and emphasizes lifestyle management strategies, such as exercise and sodium intake, to reduce post-transplant complications.
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Affiliation(s)
- Amer A Belal
- Department of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL 32610, United States
| | - Alfonso H Santos Jr
- Department of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL 32610, United States
| | - Amir Kazory
- Department of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL 32610, United States
| | - Abhilash Koratala
- Department of Nephrology, Medical College of Wisconsin, Milwaukee, WI 53226, United States
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Kanbay M, Siriopol D, Guldan M, Ozbek L, Topcu AU, Siriopol I, Tuttle K. Prognostic impact of post-transplant diabetes mellitus in kidney allograft recipients: a meta-analysis. Nephrol Dial Transplant 2025; 40:554-576. [PMID: 39134508 DOI: 10.1093/ndt/gfae185] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative not only to incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and graft loss, in kidney transplant recipients. METHODS PubMed, Ovid/Medline, Web of Science, Scopus and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and overall graft loss in adult kidney transplant recipients were included. RESULTS Fifty-three studies, encompassing a total of 138 917 patients, evaluating the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality [risk ratio (RR) 1.70, 95% confidence interval (CI) 1.53 to 1.89, P < .001] and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P < .001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P < .001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P < .001). CONCLUSION These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Dimitrie Siriopol
- Nephrology Department, "Sf. Ioan cel Nou" County Hospital, Suceava, Romania
- "Stefan cel Mare" University, Suceava, Romania
| | - Mustafa Guldan
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Lasin Ozbek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ahmet U Topcu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ianis Siriopol
- Anaesthesia and Intensive Care Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iaşi, Romania
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Katherine Tuttle
- Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA
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Popović L, Bulum T. New Onset Diabetes After Organ Transplantation: Risk Factors, Treatment, and Consequences. Diagnostics (Basel) 2025; 15:284. [PMID: 39941214 PMCID: PMC11816453 DOI: 10.3390/diagnostics15030284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
New onset diabetes mellitus after organ transplantation (NODAT) is a frequent and serious complication of solid organ transplantation. It significantly impacts graft function, patient survival, and quality of life. NODAT is diagnosed based on the criteria for type 2 diabetes, with the oral glucose tolerance test (OGTT) serving as the gold standard for diagnosis. The development of NODAT is influenced by a range of risk factors, which are classified into modifiable and non-modifiable categories. Post-transplant, regular glycemic monitoring at specific intervals is essential for timely diagnosis and initiation of therapy. Early intervention can help prevent or delay the onset of diabetes-related complications. The treatment strategy for NODAT involves lifestyle modifications and pharmacological interventions. These include medications such as metformin, sulfonylureas, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and insulin. Adjusting immunosuppressive therapy-either by reducing dosages or substituting drugs with lower diabetogenic potential-is a common preventative and therapeutic measure. However, this must be performed cautiously to avoid acute graft rejection, which poses a greater risk to the patient compared to NODAT itself. In addition to managing diabetes, addressing comorbidities such as hypertension and dyslipidemia is crucial, as they elevate the risk of cardiovascular events and mortality. Patients with NODAT are also prone to developing common diabetes-related complications, including diabetic nephropathy, neuropathy, retinopathy, and peripheral vascular disease. Therefore, regular follow-ups and appropriate treatment are vital to maintaining quality of life and improving long-term outcomes.
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Affiliation(s)
- Lucija Popović
- Department of Emergency Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - Tomislav Bulum
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Department of Diabetes and Endocrinology, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Dugi dol 4a, 10000 Zagreb, Croatia
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Qian M, Guan M, Wang L, Hu N. Tacrolimus and diabetic rodent models. Pharmacol Rep 2025:10.1007/s43440-024-00693-3. [PMID: 39836342 DOI: 10.1007/s43440-024-00693-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 12/19/2024] [Accepted: 12/29/2024] [Indexed: 01/22/2025]
Abstract
Tacrolimus (TAC) is an immunosuppressant widely utilized in organ transplantation. One of its primary adverse effects is glucose metabolism disorder, which significantly increases the risk of diabetes. Investigating the molecular mechanisms underlying TAC-induced diabetes is essential for developing effective prevention and treatment strategies for these adverse effects. In addition, TAC can induce cost-effective, non-obese animal models of diabetes, where the metabolic parameter changes closely resemble those observed during the onset and progression of type 2 diabetes (T2DM), post-transplantation diabetes mellitus (PTDM), and associated complications. This review, based on articles indexed in PubMed up to August 19, 2024, identified 48 studies focusing on TAC-induced diabetic rodent models and 22 studies exploring the effects of TAC on diabetic or obese rodent models. These studies were systematically summarized based on TAC dosage, route of administration, duration of administration, and glucose metabolism indices used for evaluation. Additionally, the impact of TAC dose reduction or discontinuation on glucose metabolism was assessed, along with pharmacological agents that modulate TAC-induced diabetes, including anti-diabetic medications, anti-inflammatory and antioxidant compounds, biologics, and antibiotics. Key signaling pathways implicated in TAC-induced diabetes include CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad, all of which impair islet β-cell function, thereby contributing to diabetes development. This review provides a concise summary of the characteristics of relevant murine models, offering valuable guidance for selecting appropriate and economical animal models for future research.
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Affiliation(s)
- Minyan Qian
- Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215127, Jiangsu, China
| | - Mengmeng Guan
- Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215127, Jiangsu, China
| | - Liying Wang
- Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China
| | - Nan Hu
- Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
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Kanbay M, Copur S, Topçu AU, Guldan M, Ozbek L, Gaipov A, Ferro C, Cozzolino M, Cherney DZI, Tuttle KR. An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management. Diabetes Obes Metab 2024; 26:2531-2545. [PMID: 38558257 DOI: 10.1111/dom.15575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/09/2024] [Accepted: 03/09/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVE Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - A Umur Topçu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mustafa Guldan
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Lasin Ozbek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Abduzhappar Gaipov
- Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Charles Ferro
- Department of Nephrology, University Hospitals Birmingham and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - David Z I Cherney
- Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada
| | - Katherine R Tuttle
- Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington, USA
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Karabulut D, Karabulut U, Kalyoncuoğlu M, Katkat F, Berber İ. Predictive value of triglyceride/glucose index for cardiac outcomes in non-diabetic renal transplant recipients. Acta Cardiol 2024; 79:319-326. [PMID: 37767903 DOI: 10.1080/00015385.2023.2257983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 08/22/2023] [Indexed: 09/29/2023]
Abstract
OBJECTIVES Insulin resistance (IR) is associated with an increased risk of adverse cardiovascular outcomes. The triglyceride-glucose index (TyG index) is a reliable marker of IR. No study has examined the impact of the TyG index on major adverse cardiac and cerebrovascular events (MACCEs) in RTRs. Therefore, this study aimed to investigate the predictive value of the TyG index for MACCEs in RTRs. MATERIALS AND METHODS Non-diabetic patients undergoing renal transplantation were retrospectively enrolled. The patients were divided into two groups according to MACCE development. The cut-off value of the TyG index for MACCE was conducted. RESULTS The mean age of 522 patients was 41 (31-51) years, and 349 (66.9%) were male. During the 5.4-year follow-up, 84 (16%) MACCE were recorded. TyG index was significantly higher in the group that developed MACCE (p < 0,001). Cox regression analysis revealed that TyG index [HR: 3.297 (1.228-8.855), p = 0.018], left ventricle ejection fraction [HR: 0.934 (0.900-0.968), p < 0.001], cadaveric transplantation [HR: 8.886 (4.764-16.576), p < 0.001], graft survey [HR: 0.608 (0.542-0.682), p < 0.001)], and smoking [HR: 1.965 (1.117-3.456), p = 0.019] were independent predictors of MACCEs in nondiabetic RTRs. CONCLUSION TyG index is an independent predictor of MACCEs in non-diabetic RTRs. The widespread use of the TyG index may positively affect long-term treatment costs and survival.
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Affiliation(s)
- Dilay Karabulut
- Cardiology Department, Bakırkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Umut Karabulut
- Cardiology Department, Acıbadem International Hospital, Istanbul, Turkey
| | - Muhsin Kalyoncuoğlu
- Cardiology Department, Haseki Sultangazi Educational and Research Hospital, Istanbul, Turkey
| | - Fahrettin Katkat
- Cardiology Department, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - İbrahim Berber
- Cardiology Department, Acıbadem International Hospital, Istanbul, Turkey
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Dung NTT, Thuy PV, Tue NT, Kien TQ, Van Duc N, Van DT, Ha DM, Ha NTT, Nghia PB, Kien NT, Van Hinh T, Nui NM, Toan PQ, Loc ND, Ha DTV, Tuyen DG, Thang LV. Neutrophil: Lymphocyte and Platelet: Lymphocyte ratios measured before transplantation and their correlation with new-onset diabetes post-transplantation in renal transplant recipients. Transpl Immunol 2024; 82:101979. [PMID: 38184212 DOI: 10.1016/j.trim.2023.101979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 11/29/2023] [Accepted: 12/31/2023] [Indexed: 01/08/2024]
Abstract
PURPOSE Our goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients. PATIENTS AND METHODS We conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test. RESULTS The overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT. CONCLUSION NLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation.
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Affiliation(s)
- Nguyen Thi Thuy Dung
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | | | - Nguyen Trí Tue
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Truong Quy Kien
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Nguyen Van Duc
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Diem Thi Van
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Do Manh Ha
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Nguyen Thi Thu Ha
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Phan Ba Nghia
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Nguyen Trung Kien
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Tran Van Hinh
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Nguyen Minh Nui
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Pham Quoc Toan
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | | | | | | | - Le Viet Thang
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam.
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Pereira Barretto L, Moreira Gomes P, Rossin Guidorizzi N, Moyses Neto M, Almeida Romao E, Garcia Chiarello P. Post-transplant diabetes mellitus: Findings in nutritional status and body composition. ENDOCRINOL DIAB NUTR 2023; 70:628-633. [PMID: 38065628 DOI: 10.1016/j.endien.2023.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 10/26/2023] [Indexed: 12/18/2023]
Abstract
INTRODUCTION Weight gain and changes in body composition are associated with the onset of diabetes after kidney transplantation, and detailing these changes can help prevent this situation. The study aimed to assess the prevalence of diabetes mellitus after kidney transplantation and changes in the nutritional status and body composition in patients with diabetes one year from surgery. MATERIALS AND METHODS This survey was a single-center, prospective cohort study. Twenty-nine patients over 18 years old who underwent isolated kidney transplantation, without diabetes, were included and followed up for one year. At hospital discharge after transplantation and one year later, anthropometric (weight, height and abdominal circumference), body composition (electrical bioimpedance), routine biochemical and dietary intake assessments were performed. RESULTS Most of the patients were male (75%), and the mean age was 48.0±11.8 years old. In the first-year post-surgery 27.6% of patients had DM and the diagnosis was made, on average, 4 months after transplantation. The group with diabetes had, from the beginning to the end of the study, greater weight and body fat, especially abdominal fat. The non-diabetic group, after one year, showed an increase in phase angle, body weight and body masses, more pronounced of fat-free mass, when compared with fat mass gain. CONCLUSIONS Both groups showed weight gain, but in the non-diabetic group these changes can be interpreted as an improvement in the nutritional profile. Metabolic abnormalities associated with immunosuppression and eating habits, combination that maintains increased the risk for diabetes for long time, keeping this group with priority in nutritional care.
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Affiliation(s)
- Laura Pereira Barretto
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil
| | - Patrícia Moreira Gomes
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil
| | - Natália Rossin Guidorizzi
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil
| | - Miguel Moyses Neto
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil
| | - Elen Almeida Romao
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil
| | - Paula Garcia Chiarello
- Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirao Preto, Sao Paulo, Brazil.
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Kwon S, Kim YC, Kwon H, Cho JH, Kim CD, Son HE, Jeong JC, Jung IM, Yoo KD, Kim Y, Lee W, Lee JS, Lee H, Lim CS, Kim YS, Kim YH, Lee JP. Metformin Use and Long-term Clinical Outcomes in Kidney Transplant Recipients. Am J Kidney Dis 2023; 82:290-299.e1. [PMID: 36965829 DOI: 10.1053/j.ajkd.2023.01.446] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 01/12/2023] [Indexed: 03/27/2023]
Abstract
RATIONALE & OBJECTIVE Metformin has been recommended for some patients with advanced chronic kidney disease. However, the value of metformin in kidney transplant recipients (KTRs) with pretransplant diabetes mellitus (DM) or posttransplant DM is uncertain. We investigated the clinical effects of metformin in KTRs. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS A total of 1,995 KTRs with diabetes from 6 tertiary referral centers in the Republic of Korea. EXPOSURE Metformin usage was defined as the use of metformin for>90 days after kidney transplantation; 1,193 KTRs were metformin users, and 802 KTRs did not use metformin. Changing usage of metformin among those exposed for >90 days was also characterized. OUTCOME Primary outcomes were all-cause mortality and death-censored graft failure (DCGF). Secondary outcomes were biopsy-proven acute rejection (BPAR) and lactic acidosis events. ANALYTICAL APPROACH Survival analyses were conducted using multivariable Cox regression and competing risk analyses using Fine and Gray models. Changes in metformin use over time were modeled using a time-varying covariate. Metformin usage, mean daily dose, and hemoglobin A1c (HbA1c) changes were considered in the landmark analysis to address time-varying confounding. RESULTS Metformin use was associated with a lower risk of DCGF (adjusted hazard ratio [AHR], 0.47 [95% CI, 0.23-0.96], P=0.038); there was no significant association with all-cause mortality (AHR, 0.94 [95% CI, 0.32-2.76], P=0.915) or BPAR (AHR 0.98 [95% CI, 0.62-1.54], P=0.942). In the subgroup analysis, metformin usage was associated with a reduced risk of all-cause mortality and a lower risk of DCGF for both pretransplantation DM and posttransplant DM groups. Metformin usage was associated with a lower risk of BPAR in the posttransplant DM group, although it was less effective in the pretransplantation DM group. There was no confirmed case of metformin-associated lactic acidosis (MALA) in the present cohort. A higher dose of metformin was correlated with lower risks of DCGF and BPAR. LIMITATIONS Data on newer antidiabetic drugs such as SGLT2 inhibitors are limited, and there is potential limited generalizability to other populations. CONCLUSIONS Metformin usage may benefit KTRs, as evidenced by its association with a reduced risk of DCGF and the absence of MALA events. Randomized controlled trials are needed to validate these observational findings.
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Affiliation(s)
- Soie Kwon
- Department of Internal Medicine, Heukseok Hospital, Chung-Ang University, Seoul, Korea; Department of Clinical Medical Sciences, College of Medicine
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital Seoul, Korea
| | - Hyunwook Kwon
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
| | - Jang-Hee Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyung-Eun Son
- Department of Internal Medicine, Gwangmyeong Hospital, Chung-Ang University, Gyeonggi-do, South Korea; Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Jong-Cheol Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea
| | - In Mok Jung
- Department of Surgery, Boramae Medical Center, Seoul, Korea
| | - Kyung Don Yoo
- Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Yeonjin Kim
- Department of Public Health Sciences, Graduate School of Public Health
| | - Woojoo Lee
- Department of Public Health Sciences, Graduate School of Public Health
| | - Jong Soo Lee
- Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University Hospital Seoul, Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Boramae Medical Center, Seoul, Korea; Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University Hospital Seoul, Korea; Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea
| | - Young Hoon Kim
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
| | - Jung Pyo Lee
- Department of Internal Medicine, Boramae Medical Center, Seoul, Korea; Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea.
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Nasir SO, McCarthy H, Mohamed Ahmed IAR. Prevalence and Risk Factors of New-onset Diabetes after Transplant in East Africans. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2023; 34:331-336. [PMID: 38345588 DOI: 10.4103/1319-2442.395449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2024] Open
Abstract
Very little is known about the prevalence of new-onset diabetes after transplant (NODAT) in sub-Saharan and Eastern Africans. Most of the data are related to African Americans and to North and South Africans. The aims of this study were to examine the prevalence of NODAT in Sudanese renal transplant recipients, compare it with the published literature, and identify the risk factors for developing NODAT. In total, 150 patients who received a living-related kidney transplant between January 2015 and January 2016 were included in this study. Patients with diabetic nephropathy and pretransplant diabetes were excluded. Follow-up was for 2 years after the transplant. The variables studied were age, sex, body mass index, a family history of diabetes mellitus (DM), pretransplant steroid therapy, dyslipidemia, and hepatitis C virus infection. Twenty- three patients (15.3%) developed NODAT during the study period. The mean age of the patients who developed NODAT was 39 ± 14 years, and the mean time to develop NODAT was 5.78 ± 5.9 months. In the multivariate analysis, the risk factors for developing NODAT were a family history of DM (P = 0.01) and pretransplant steroid therapy (P = 0.01). The prevalence of NODAT in this study was 15.3%, which is in line with the reported literature from North Africa. However, it was significantly lower than the reported prevalence in African Americans.
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Affiliation(s)
- Salsabil Osman Nasir
- Deparment of Clinical Pharmacology, School of Pharmacy, Queen's University, Belfast, United Kingdom
| | - Helen McCarthy
- Deparment of Clinical Pharmacology, School of Pharmacy, Queen's University, Belfast, United Kingdom
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González Delgado A, Hernández AF, Marrero D, Maside AF, Barroso GH, Carreño EP, Acosta Sørensen C, Rodríguez-Rodríguez AE, Collantes T, Anabel R, Álvarez CR, Rivero A, Jiménez Sosa A, Macia M, Terán García E, Álvarez González A, González Rinne A, Rodríguez A, Redondo EDB, Rodríguez Adanero C, Hernández D, Torres Ramírez A, Porrini E. Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study. Nephron Clin Pract 2023; 147:560-571. [PMID: 37276852 DOI: 10.1159/000531334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/13/2023] [Indexed: 06/07/2023] Open
Abstract
INTRODUCTION Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1β, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.
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Affiliation(s)
| | | | - Domingo Marrero
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Andrés Franco Maside
- Central Laboratory, Immunology Unit, Hospital Universitario de Canarias (HUC), Tenerife, Spain
| | | | | | | | | | - Tatiana Collantes
- Hospital Clínico de la Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Rodríguez Anabel
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | - Antonio Rivero
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | - Manuel Macia
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | | | | | - Aurelio Rodríguez
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | | | | | - Domingo Hernández
- Nephrology Service, Hospital Regional Universitario de Málaga, Universidad de Málaga, IBIMA, Málaga, Spain
| | - Armando Torres Ramírez
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
| | - Esteban Porrini
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
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Education and Psychosocial Factors Predict Odds of Death After Transfer to Adult health Care in Pediatric Liver Transplant Patients. J Pediatr Gastroenterol Nutr 2022; 75:623-628. [PMID: 35767565 DOI: 10.1097/mpg.0000000000003549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To analyze demographic, psychosocial, and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer. METHODS A retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000 and 2015. RESULTS During the study period, 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while 8 were lost to follow up. In total 23 of 93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race [odds ratio (OR) 6.59, P < 0.001]; psychiatric illness or substance use (OR 2.81, P = 0.04); failure to graduate high school before transfer (OR 9.59, P < 0.001); posttransplant tacrolimus medication-level variability index >2.5 (OR 5.36, P = 0.04); provider documentation of medication nonadherence (OR 4.72, P = 0.02); acute cellular rejection (OR 4.44, P = 0.03); the presence of diabetes mellitus (OR 5.71, P = 0.001), and chronic kidney disease (OR 2.82, P = 0.04). Failure to graduate HS was associated with loss to follow up ( P < 0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each P < 0.05). CONCLUSIONS Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.
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Barroso Hernández S, Álvarez López Á, Rodríguez Sabillón JA, López Arnaldo C, Hernández Gallego R, García de Vinuesa Calvo E, Villa Rincón J, Díaz Campillejo RM, Robles Pérez-Monteoliva NR. Effect of weight change after renal transplantation on outcomes of graft survival. Nefrologia 2022; 42:568-577. [PMID: 36681517 DOI: 10.1016/j.nefroe.2021.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 06/22/2021] [Accepted: 08/02/2021] [Indexed: 06/17/2023] Open
Abstract
BACKGROUND AND OBJECTIVE After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. PATIENTS AND METHODS Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. RESULTS Globally, there was an average weight gain of 4.5 kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, p = 0.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, p = 0.003), and BMI before transplantation (OR 0.9, p = 0.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, p = 0.003), and obesity, with a worse evolution (HR 7.0, p = 0.025). CONCLUSIONS Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival.
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Affiliation(s)
| | | | | | | | | | | | - Juan Villa Rincón
- Servicio de Nefrología, Hospital Universitario de Badajoz, Badajoz, Spain
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14
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Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes. Nat Med 2022; 28:999-1005. [PMID: 35393535 DOI: 10.1038/s41591-022-01758-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 02/24/2022] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1-71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8-65.8%) for the clinical characteristics model (P = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07-5.00) (P = 1.92 × 10-7) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.
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Axelrod DA, Cheungpasitporn W, Bunnapradist S, Schnitzler MA, Xiao H, McAdams-DeMarco M, Caliskan Y, Bae S, Ahn JB, Segev DL, Lam NN, Hess GP, Lentine KL. Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients. Kidney Med 2022; 4:100377. [PMID: 35072042 PMCID: PMC8767140 DOI: 10.1016/j.xkme.2021.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
RATIONALE & OBJECTIVE Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. STUDY DESIGN Retrospective database study. SETTING & PARTICIPANTS Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. EXPOSURES Various immunosuppression regimens in the first 3 months after transplant. OUTCOMES Development of DM >3 months-to-1 year posttransplant. ANALYTICAL APPROACH We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. RESULTS 12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs <55 years: 16.7% vs 10.1%) and obese (body mass index [BMI] ≥ 30 kg/m2 vs BMI < 30 kg/m2: 17.1% vs 10.9%) patients. The incidence of posttransplant DM was lower with steroid avoidance [TMG/ALEM + no prednisone (8.4%) and IL2rAb + no prednisone (9.7%)] than TMG/ALEM with triple therapy (13.1%). After adjustment for donor and recipient characteristics, TMG/ALEM with steroid avoidance was beneficial for all groups [age < 55 years: adjusted HR (aHR), 0.63 (95% confidence interval [CI], 0.54-0.72); age ≥ 55 years: aHR, 0.69 (95% CI, 0.60-0.79); BMI < 30 kg/m2: aHR, 0.69 (95% CI, 0.60-0.78); BMI ≥ 30 kg/m2: aHR, 0.67 (95% CI, 0.57-0.79)]. However, IL2rAb with steroid avoidance was beneficial only for older patients (aHR, 0.76; 95% CI, 0.58-0.99) and for those with BMI < 30 kg/m2 (aHR, 0.63; 95% CI, 0.46-0.87). LIMITATIONS Retrospective study and lacked data on immunosuppression levels. CONCLUSIONS The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.
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Affiliation(s)
| | | | | | - Mark A. Schnitzler
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | - Huiling Xiao
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | | | - Yasar Caliskan
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | - Sunjae Bae
- Johns Hopkins School of Medicine, Baltimore, Maryland
| | - JiYoon B. Ahn
- Johns Hopkins School of Medicine, Baltimore, Maryland
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Bashier AM, Kumar D, Alalawi FJ, Al Nour H, Al Hadari AK, Bin Hussain AA. Post-Transplant Diabetes: Prevalence, Risk, and Management Challenges. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2022. [DOI: 10.1159/000522092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The prevalence of diabetes and diabetic nephropathy is increasing, especially in middle eastern countries. Many patients reach end-stage renal disease and either start dialysis or consider preemptive transplantation. Even a higher number of patients develop post-transplant diabetes, which imposes an even higher risk on graft survival and outcomes post-transplantation. Recently, in the UAE, a renal transplant service has been initiated. Because the population is considered at high risk for post-transplant diabetes, we wrote this review article to discuss the prevalence, risk factors, diagnostic criteria, and management, including lifestyle interventions, manipulation of immunosuppressant agents, and suggested algorithms for the use of oral hypoglycemic agents used in the management of post-transplantation diabetes mellitus. We also discussed the specific indications for each of the oral hypoglycemic agents.
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Multani EK, Bajwa D, Multani PK, Nobakht E, Raj D, Paul RS, Paul RS. EYE DISEASE IN KIDNEY TRANSPLANTATION: CLINICAL CHALLENGES IN A UNIQUE PATIENT POPULATION. Surv Ophthalmol 2021; 67:1252-1269. [PMID: 34954092 DOI: 10.1016/j.survophthal.2021.12.007] [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: 10/28/2020] [Revised: 12/14/2021] [Accepted: 12/20/2021] [Indexed: 11/30/2022]
Abstract
Eye disease is common among kidney transplant recipients and their management is challenging. Chronic kidney disease is associated with ocular complications, both independently and in the context of various systemic disorders. In addition, chronic immunosuppression predisposes kidney transplant recipients to an array of long-term ocular issues. This may be broadly categorized into infections, malignancies, and other immunosuppression-specific side effects. The interdependence of kidney disease, transplant pharmacotherapy and ocular health therefore requires a multispecialty approach. Although the kidney transplant population has grown along with the burden of associated oculopathies, systematic guidelines targeting this patient group are lacking. This evidenced-based narrative review summarizes the pertinent issues that may present in the ophthalmic and optometric clinical settings, with emphasis on collaborative management and directions for future research.
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Affiliation(s)
- Eisha K Multani
- MY EYE DR OPTOMETRISTS LLC, 1330 CONNECTICUT AVE NW, WASHINGTON DC, 20037, UNITED STATES
| | - Dalvir Bajwa
- THE NEWCASTLE UPON TYNE HOSPITALS, NHS FOUNDATION TRUST, ROYAL VICTORIA INFIRMARY, QUEEN VICTORIA ROAD, NEWCASTLE UPON TYNE NE1 4LP, UNITED KINGDOM
| | - Priyanika K Multani
- INLAND VISION CENTER OPTOMETRY, 473 E CARNEGIE DR, SUITE 100, SAN BERNADINO, CA 92408
| | - Ehsan Nobakht
- DIVISION OF KIDNEY DISEASE & HYPERTENSION, GEORGE WASHINGTON UNIVERSITY, 2150 PENNSYVANIA AVENUE, SUITE 3-438, WASHINGTON DC, 20037, UNITED STATES
| | - Dominic Raj
- DIVISION OF KIDNEY DISEASE & HYPERTENSION, GEORGE WASHINGTON UNIVERSITY, 2150 PENNSYVANIA AVENUE, SUITE 3-438, WASHINGTON DC, 20037, UNITED STATES
| | - Rohan S Paul
- DIVISION OF KIDNEY DISEASE & HYPERTENSION, GEORGE WASHINGTON UNIVERSITY, 2150 PENNSYVANIA AVENUE, SUITE 3-438, WASHINGTON DC, 20037, UNITED STATES
| | - Rohan S Paul
- DIVISION OF KIDNEY DISEASE & HYPERTENSION, GEORGE WASHINGTON UNIVERSITY, 2150 PENNSYVANIA AVENUE, SUITE 3-438, WASHINGTON DC, 20037, UNITED STATES.
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Terrec F, Jouve T, Malvezzi P, Janbon B, Naciri Bennani H, Rostaing L, Noble J. Belatacept Use after Kidney Transplantation and Its Effects on Risk of Infection and COVID-19 Vaccine Response. J Clin Med 2021; 10:jcm10215159. [PMID: 34768680 PMCID: PMC8585113 DOI: 10.3390/jcm10215159] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 10/26/2021] [Accepted: 11/02/2021] [Indexed: 02/07/2023] Open
Abstract
Introduction: Belatacept is a common immunosuppressive therapy used after kidney transplantation (KT) to avoid calcineurin-inhibitor (CNI) use and its related toxicities. It is unclear whether its use exposes KT recipients (KTx) to a greater risk of infection or a poorer response to vaccines. Areas covered: We reviewed PubMed and the Cochrane database. We then summarized the mechanisms and impacts of belatacept use on the risk of infection, particularly opportunistic, in two settings, i.e., de novo KTx and conversion from CNIs. We also focused on COVID-19 infection risk and response to SARS-CoV-2 vaccination in patients whose maintenance immunosuppression relies on belatacept. Expert opinion: When belatacept is used de novo, or after drug conversion the safety profile regarding the risk of infection remains good. However, there is an increased risk of opportunistic infections, mainly CMV disease and Pneumocystis pneumonia, particularly in those with a low eGFR, in older people, in those receiving steroid-based therapy, or those that have an early conversion from CNI to belatacept (i.e., <six months post-transplantation). Thus, we recommend, if possible, delaying conversion from CNI to belatacept until at least six months post-transplantation. Optimal timing seems to be eight months post-transplantation. In addition, KTx receiving belatacept respond poorly to SARS-CoV-2 vaccination.
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Affiliation(s)
- Florian Terrec
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
| | - Thomas Jouve
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
- School of Medicine, Université Grenoble Alpes, 38043 Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
| | - Bénédicte Janbon
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
| | - Hamza Naciri Bennani
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
- School of Medicine, Université Grenoble Alpes, 38043 Grenoble, France
- Correspondence: ; Tel.: +33-4-76-76-54-60
| | - Johan Noble
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire Grenoble Alpes (CHU), Université Grenoble Alpes, 38043 Grenoble, France; (F.T.); (T.J.); (P.M.); (B.J.); (H.N.B.); (J.N.)
- School of Medicine, Université Grenoble Alpes, 38043 Grenoble, France
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Vranic G, Cooper M. But Why Weight: Understanding the Implications of Obesity in Kidney Transplant. Semin Nephrol 2021; 41:380-391. [PMID: 34715967 DOI: 10.1016/j.semnephrol.2021.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Obesity is increasing in prevalence among candidates for kidney transplant. Understanding the influence of obesity on candidate evaluation, surgical risk, peritransplant management, and post-transplant outcomes is critical to ensuring equitable access to transplant for this growing population.
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Affiliation(s)
- Gayle Vranic
- MedStar Georgetown Transplant Institute, Georgetown University, Washington, DC.
| | - Matthew Cooper
- MedStar Georgetown Transplant Institute, Georgetown University, Washington, DC
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20
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Pham Vu T, Can Van M, Dang Thanh C, Nguyen Minh T, Nguyen Trung K, Nguyen Duy T, Do Q, Tran Viet T, Le Viet T. Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new-onset diabetes after transplantation. J Clin Lab Anal 2021; 35:e24000. [PMID: 34519108 PMCID: PMC8551688 DOI: 10.1002/jcla.24000] [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: 07/18/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To evaluate serum adiponectin and leptin concentration in new-onset diabetes after transplantation (NODAT) and non-NODAT patients and association with renal function in kidney transplant recipients (KTRs). PATIENTS AND METHODS A study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines. RESULTS In the NODAT group, the median level of serum adiponectin was lower than that of non-NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non-RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non-NODAT, and all subject groups, based on univariate and multivariate linear regression analysis. CONCLUSION New-onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.
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Affiliation(s)
- Thuy Pham Vu
- Kinh 7 Charity ClinicKien GiangViet Nam
- Vietnam Military Medical UniversityHa NoiViet Nam
| | - Mao Can Van
- Vietnam Military Medical UniversityHa NoiViet Nam
| | | | | | - Kien Nguyen Trung
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Toan Nguyen Duy
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Quyet Do
- Vietnam Military Medical UniversityHa NoiViet Nam
| | - Tien Tran Viet
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Thang Le Viet
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
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21
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Barroso Hernández S, Álvarez López Á, Rodríguez Sabillón JA, López Arnaldo C, Hernández Gallego R, García de Vinuesa Calvo E, Villa Rincón J, Díaz Campillejo RM, Robles Pérez-Monteoliva NR. Effect of weight change after renal transplantation on outcomes of graft survival. Nefrologia 2021; 42:S0211-6995(21)00163-6. [PMID: 34521566 DOI: 10.1016/j.nefro.2021.08.001] [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: 01/09/2021] [Revised: 06/22/2021] [Accepted: 08/02/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVE After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. PATIENTS AND METHODS Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. RESULTS Globally, there was an average weight gain of 4.5kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, P=.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, P=.003), and BMI before transplantation (OR 0.9, P=.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, P=.003), and obesity, with a worse evolution (HR 7.0, P=.025). CONCLUSIONS Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival.
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Affiliation(s)
| | | | | | | | | | | | - Juan Villa Rincón
- Servicio de Nefrología, Hospital Universitario de Badajoz, Badajoz, España
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Prasad GVR, Bhamidi V. Managing cardiovascular disease risk in South Asian kidney transplant recipients. World J Transplant 2021; 11:147-160. [PMID: 34164291 PMCID: PMC8218347 DOI: 10.5500/wjt.v11.i6.147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/12/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
South Asians (SA) are at higher cardiovascular risk than other ethnic groups, and SA kidney transplant recipients (SA KTR) are no exception. SA KTR experience increased major adverse cardiovascular events both early and late post-transplantation. Cardiovascular risk management should therefore begin well before transplantation. SA candidates may require aggressive screening for pre-transplant cardiovascular disease (CVD) due to their ethnicity and comorbidities. Recording SA ethnicity during the pre-transplant evaluation may enable programs to better assess cardiovascular risk, thus allowing for earlier targeted peri- and post-transplant intervention to improve cardiovascular outcomes. Diabetes remains the most prominent post-transplant cardiovascular risk factor in SA KTR. Diabetes also clusters with other metabolic syndrome components including lower high-density lipoprotein cholesterol, higher triglycerides, hypertension, and central obesity in this population. Dyslipidemia, metabolic syndrome, and obesity are all significant CVD risk factors in SA KTR, and contribute to increased insulin resistance. Novel biomarkers such as adiponectin, apolipoprotein B, and lipoprotein (a) may be especially important to study in SA KTR. Focused interventions to improve health behaviors involving diet and exercise may especially benefit SA KTR. However, there are few interventional clinical trials specific to the SA population, and none are specific to SA KTR. In all cases, understanding the nuances of managing SA KTR as a distinct post-transplant group, while still screening for and managing each CVD risk factor individually in all patients may help improve the long-term success of all kidney transplant programs catering to multi-ethnic populations.
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Affiliation(s)
- G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
| | - Vaishnavi Bhamidi
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
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Mpratsiakou A, Papasotiriou M, Ntrinias T, Tsiotsios K, Papachristou E, Goumenos DS. Safety and Efficacy of Long-Term Administration of Dipeptidyl peptidase IV Inhibitors in Patients With New Onset Diabetes After Kidney Transplant. EXP CLIN TRANSPLANT 2021; 19:411-419. [PMID: 34053420 DOI: 10.6002/ect.2020.0519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES The appearance of new onset diabetes is common after kidney transplant. Treatment options are limited because of renal function-related contraindications, interactions with immunosuppressive drugs, and side effects. We investigated the long-term safety and efficacy of dipeptidyl peptidase IV inhibitors in renal transplant recipients with new onset diabetes. MATERIALS AND METHODS We treated 12 patients with dipeptidyl peptidase IV inhibitors, and 5 patients received insulin monotherapy as initial treatment of new onset diabetes after kidney transplant. All patients were followed for 12 months after diagnosis. Glycosylated hemoglobin A1c, estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight were measured during outpatient visits. Effects of dipeptidyl peptidase IV inhibitors and insulin on the aforementioned parameters were measured to compare values at time of diagnosis versus mean values of the last 6 months of follow-up. RESULTS Patients were treated with linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients), and alogliptin (2 patients). Patients had a mean age of 59.4 ± 12 years and a mean glycosylated hemoglobin A1c of 6.6% at diagnosis, which was decreased to 6.1% (P = .03) at 1 year of follow-up. Renal function remained stable, and plasma tacrolimus levels did not appear to be affected. No significant differences were shown in serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels aftertreatment. Nevertheless,triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dL; P = .0039). A decrease in body weight was also observed. Finally, patients treated with dipeptidyl peptidase V inhibitors achieved better glycosylated hemoglobin A1c levels than those treated with insulin. CONCLUSIONS Dipeptidyl peptidase IV inhibitors appear to be a safe, effective, and hypoglycemia-free option fortreatment of new onset diabetes in renaltransplant recipients and possibly provide better diabetes control than insulin therapy.
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Affiliation(s)
- Adamantia Mpratsiakou
- From the Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece
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Pham Vu T, Nguyen Thi Thuy D, Truong Quy K, Nguyen Thi Thu H, Nguyen Van D, Diem Thi V, Do Manh H, Nguyen Trung K, Do Q, Tran Viet T, Do Nhu B, Pham Quoc T, Can Van M, Le Viet T. Serum hs-CRP measured prior transplantation predicts of new-onset diabetes after transplantation in renal transplant recipients. Transpl Immunol 2021; 66:101392. [PMID: 33838297 DOI: 10.1016/j.trim.2021.101392] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/29/2021] [Accepted: 04/04/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND To assess the incidence of new-onset diabetes after transplantation (NODAT) for the first year post-transplantation and the predictive value of high-sensitivity C-reactive Protein (hs-CRP) before transplantation for NODAT prediction in kidney transplantation patients. MATERIAL AND METHODS A study of 251 consecutive adult end-stage kidney disease patients transplanted kidneys from living donors, follow-up during the first year to find NODAT. We diagnosed NODAT based on blood glucose or HbA1c following to the criteria of the American Diabetes Association. RESULTS The ratio of NODAT was 12.4%. The mean age, mean BMI, the proportion of arteriosclerosis, and the median hs-CRP level in NODAT group were significantly higher than those of non-NODAT group with p < 0.05. Age, BMI and serum hs-CRP had a predictive value for NODAT (Age: AUC = 0.62, p < 0.05, BMI: AUC = 0.626, hs-CRP: AUC = 0.748, p < 0.001). CONCLUSION Serum hs-CRP level measured prior transplantation is a good predictor for NODAT in renal transplant recipients.
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Affiliation(s)
- Thuy Pham Vu
- Kinh 7 Charity Clinic, Kien Giang, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Dung Nguyen Thi Thuy
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Kien Truong Quy
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | | | - Duc Nguyen Van
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Van Diem Thi
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Ha Do Manh
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Kien Nguyen Trung
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Quyet Do
- Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Tien Tran Viet
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Binh Do Nhu
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Toan Pham Quoc
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Mao Can Van
- Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Thang Le Viet
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam.
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25
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Rysz J, Franczyk B, Radek M, Ciałkowska-Rysz A, Gluba-Brzózka A. Diabetes and Cardiovascular Risk in Renal Transplant Patients. Int J Mol Sci 2021; 22:3422. [PMID: 33810367 PMCID: PMC8036743 DOI: 10.3390/ijms22073422] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/05/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Maciej Radek
- Department of Neurosurgery, Surgery of Spine and Peripheral Nerves, Medical University of Lodz, 90-549 Lodz, Poland;
| | | | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
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26
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Sotomayor CG, Oskooei SS, Bustos NI, Nolte IM, Gomes-Neto AW, Erazo M, Gormaz JG, Berger SP, Navis GJ, Rodrigo R, Dullaart RPF, Bakker SJL. Serum uric acid is associated with increased risk of posttransplantation diabetes in kidney transplant recipients: a prospective cohort study. Metabolism 2021; 116:154465. [PMID: 33316268 DOI: 10.1016/j.metabol.2020.154465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/23/2020] [Accepted: 12/09/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND Serum uric acid (SUA) is associated with fasting glucose in healthy subjects, and prospective epidemological studies have shown that elevated SUA is associated with increased risk of type 2 diabetes. Whether SUA is independently associated with higher risk of posttransplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTR) remains unknown. METHODS We performed a longitudinal cohort study of 524 adult KTR with a functioning graft ≥1-year, recruited at a university setting (2008-2011). Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the association between time-updated SUA and risk of PTDM (defined according the American Diabetes Association's diagnostic criteria). RESULTS Mean (SD) SUA was 0.43 (0.11) mmol/L at baseline. During 5.3 (IQR, 4.1-6.0) years of follow-up, 52 (10%) KTR developed PTDM. In univariate prospective analyses, SUA was associated with increased risk of PTDM (HR 1.75, 95% CI 1.36-2.26 per 1-SD increment; P < 0.001). This finding remained materially unchanged after adjustment for components of the metabolic syndrome, lifestyle, estimated glomerular filtration rate, immunosuppressive therapy, cytomegalovirus and hepatitis C virus infection (HR 1.89, 95% CI 1.32-2.70; P = 0.001). These findings were consistent in categorical analyses, and robust in sensitivity analyses without outliers. CONCLUSIONS In KTR, higher SUA levels are strongly and independently associated with increased risk of PTDM. Our findings are in agreement with accumulating evidence supporting SUA as novel independent risk marker for type 2 diabetes, and extend the evidence, for the first time, to the clinical setting of outpatient KTR.
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Affiliation(s)
- Camilo G Sotomayor
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
| | - Sara Sokooti Oskooei
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | | | - Ilja M Nolte
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - António W Gomes-Neto
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Marcia Erazo
- Faculty of Medicine, University of Chile, Santiago, Chile
| | - Juan G Gormaz
- Faculty of Medicine, University of Chile, Santiago, Chile
| | - Stefan P Berger
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Gerjan J Navis
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Ramón Rodrigo
- Faculty of Medicine, University of Chile, Santiago, Chile
| | - Robin P F Dullaart
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Stephan J L Bakker
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Impact of Pretransplant and New-Onset Diabetes After Transplantation on the Risk of Major Adverse Cardiovascular Events in Kidney Transplant Recipients: a Population-Based Cohort Study. Transplantation 2021; 105:2470-2481. [PMID: 33560726 DOI: 10.1097/tp.0000000000003639] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Pretransplant diabetes and new onset diabetes after transplant (NODAT) are known risk factors for vascular events after kidney transplantation but the incidence and magnitude of the risk of major adverse cardiovascular events (MACE) and cardiac deaths remains uncertain in recent era. METHODS A population cohort study of kidney transplant recipients identified using data from linked administrative healthcare databases from Ontario, Canada. The incidence rates of MACE (expressed as events with 95% confidence interval (95%CI) per 1000-person-years were reported according to diabetes status of pretransplant diabetes, NODAT or no diabetes. Extended Cox regression model was used to examine the association between diabetes status, MACE and cardiac death. RESULTS Of 5248 recipients, 1973 (38%) had pretransplant diabetes and 799 (15%) developed NODAT with a median follow-up of 5.5 years. The incidence rates (95%CI) of MACE for recipients with pretransplant diabetes, NODAT and no diabetes between 1-3 years posttransplant were 38.1 (32.1-45.3), 12.6 (6.3-25.2) and 11.8 (9.2-15.0) per 1000-person-years, respectively. Compared to recipients with pretransplant diabetes, recipients with NODAT experienced a lower risk of MACE (adjusted hazard ratio [HR]0.59, 95%CI 0.47-0.74]), but not cardiac death [0.97(0.61-1.55)]. The rate of MACE and cardiac death was lowest in patients without diabetes. CONCLUSIONS Patients with pretransplant diabetes incur the greatest rate of MACE and cardiac deaths after transplantation. Having NODAT also bear high burden of vascular events compared to those without diabetes, but the magnitude of the increased rate remains lower than recipients with pretransplant diabetes.
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28
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Kim HD, Chang JY, Chung BH, Kim CD, Lee SH, Kim YH, Yang CW. Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial. Ann Transplant 2021; 26:e927984. [PMID: 33479188 PMCID: PMC7836319 DOI: 10.12659/aot.927984] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background This randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT). Material/Methods Seventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the “EVL group” (n=38) and the “TAC group” (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group. Results The 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively). The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group. Conclusions EVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.
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Affiliation(s)
- Hyung Duk Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ji-Yeun Chang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Byung Ha Chung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, Kyungpook National University School of Medicine, Deagu, South Korea
| | - Sang-Ho Lee
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, South Korea
| | - Yeong Hoon Kim
- Department of Internal Medicine, College of Medicine, Inje University, Pusan, South Korea
| | - Chul Woo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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Chevallier E, Jouve T, Rostaing L, Malvezzi P, Noble J. pre-existing diabetes and PTDM in kidney transplant recipients: how to handle immunosuppression. Expert Rev Clin Pharmacol 2020; 14:55-66. [PMID: 33196346 DOI: 10.1080/17512433.2021.1851596] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Preexisting diabetes (PD) and post-transplant diabetes mellitus (PTDM) are common and severe comorbidities posttransplantation. The immunosuppressive regimens are modifiable risk factors. AREAS COVERED We reviewed Pubmed and Cochrane database and we summarize the mechanisms and impacts of available immunosuppressive treatments on the risk of PD and PTDM. We also assess the possible management of these drugs to improve glycemic parameters while considering risks inherent in transplantation. EXPERT OPINION PD i) increases the risk of sepsis, ii) is an independent risk factor for infection-related mortality, and iii) increases acute rejection risk. Regarding PTDM development i) immunosuppressive strategies without corticosteroids significantly reduce the risk but the price may be a higher incidence of rejection; ii) minimization or rapid withdrawal of steroids are two valuable approaches; iii) the diabetogenic role of calcineurin inhibitors(CNIs) is also well-described and is more important for tacrolimus than for cyclosporine. Reducing tacrolimus-exposure may improve glycemic parameters but also has a higher risk of rejection. PTDM risk is higher in patients that receive sirolimus compared to mycophenolate mofetil. Finally, conversion from CNIs to belatacept may offer the best benefits to PTDM-recipients in terms of glycemic parameters, graft and patient-outcomes.
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Affiliation(s)
- Eloi Chevallier
- Service De Néphrologie, Hémodialyse, Aphérèses Et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble, France
| | - Thomas Jouve
- Service De Néphrologie, Hémodialyse, Aphérèses Et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble, France.,Université Grenoble Alpes , Grenoble, France
| | - Lionel Rostaing
- Service De Néphrologie, Hémodialyse, Aphérèses Et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble, France.,Université Grenoble Alpes , Grenoble, France
| | - Paolo Malvezzi
- Service De Néphrologie, Hémodialyse, Aphérèses Et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble, France
| | - Johan Noble
- Service De Néphrologie, Hémodialyse, Aphérèses Et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble, France
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Bertrand D, Terrec F, Etienne I, Chavarot N, Sberro R, Gatault P, Garrouste C, Bouvier N, Grall-Jezequel A, Jaureguy M, Caillard S, Thervet E, Colosio C, Golbin L, Rerolle JP, Thierry A, Sayegh J, Janbon B, Malvezzi P, Jouve T, Rostaing L, Noble J. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort. J Clin Med 2020; 9:jcm9113479. [PMID: 33126667 PMCID: PMC7693007 DOI: 10.3390/jcm9113479] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/22/2020] [Accepted: 10/26/2020] [Indexed: 12/21/2022] Open
Abstract
Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13-431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/- 13 months. OPIs developed in 42(9.3%) patients after 14 +/- 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%; p < 0.001; and 11.6% vs. 2.4%, p < 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person-years. Incidence of CMV disease was 2.8/100 person-years, of pneumocystis pneumonia 1.6/100 person-years, and of aspergillosis 0.2/100 person-years. Multivariate analyses showed that estimated glomerular filtration (eGFR) < 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 - 10.3), p < 0.001). The incidence of EBV DNAemia was 17.3 events /100 person-years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/- 18 mL/min/1.73 m2 to 42.2 +/- 18 mL/min/1.73 m2 (p < 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.
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Affiliation(s)
- Dominique Bertrand
- Department of Nephrology and Transplantation, Rouen University Hospital, 76000 Rouen, France; (D.B.); (I.E.)
| | - Florian Terrec
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
| | - Isabelle Etienne
- Department of Nephrology and Transplantation, Rouen University Hospital, 76000 Rouen, France; (D.B.); (I.E.)
| | - Nathalie Chavarot
- Department of Adult Kidney Transplantation, Necker-Enfants Malades University Hospital, 75000 Paris, France; (N.C.); (R.S.)
| | - Rebecca Sberro
- Department of Adult Kidney Transplantation, Necker-Enfants Malades University Hospital, 75000 Paris, France; (N.C.); (R.S.)
| | - Philippe Gatault
- Department of Nephrology, Tours University Hospital, 37000 Tours, France;
| | - Cyril Garrouste
- Department of Nephrology, Clermont Ferrand University Hospital, 63000 Clermont Ferrand, France;
| | - Nicolas Bouvier
- Department of Nephrology, Caen University Hospital, 14000 Caen, France;
| | | | - Maïté Jaureguy
- Department of Nephrology, Amiens University Hospital, 80000 Amiens, France;
| | - Sophie Caillard
- Department of Nephrology, Strasbourg University Hospital, 67000 Strasbourg, France;
| | - Eric Thervet
- Department of Nephrology, European Georges Pompidou University Hospital, 75000 Paris, France;
| | - Charlotte Colosio
- Department of Nephrology, Reims University Hospital, 51100 Reims, France;
| | - Leonard Golbin
- Department of Nephrology, Rennes University Hospital, 35000 Rennes, France;
| | | | - Antoine Thierry
- Department of Nephrology, Poitiers University Hospital, 86000 Poitiers, France;
| | - Johnny Sayegh
- Department of Nephrology, Angers University Hospital, 49000 Angers, France;
| | - Bénédicte Janbon
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
| | - Paolo Malvezzi
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
| | - Thomas Jouve
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
- Department of Adult Kidney Transplantation, Necker-Enfants Malades University Hospital, 75000 Paris, France; (N.C.); (R.S.)
| | - Lionel Rostaing
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
- Department of Adult Kidney Transplantation, Necker-Enfants Malades University Hospital, 75000 Paris, France; (N.C.); (R.S.)
- Correspondence: ; Tel.: +33-4-76-76-54-60
| | - Johan Noble
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (F.T.); (B.J.); (P.M.); (T.J.); (J.N.)
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Gray JN, Wolf-Doty T, Sulejmani N, Gaber O, Axelrod D, Abdalla B, Danovitch G. KidneyCare Guided Immuno-Optimization in Renal Allografts: The KIRA Protocol. Methods Protoc 2020; 3:E68. [PMID: 33007896 PMCID: PMC7712506 DOI: 10.3390/mps3040068] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 09/20/2020] [Accepted: 09/25/2020] [Indexed: 01/09/2023] Open
Abstract
Immunosuppressant agents are essential in every transplant recipient's care yet walking the fine line of over- or under-immunosuppression is a constant struggle for both patients and transplant providers alike. Optimization and personalization of immunosuppression has been limited by the need for non-invasive graft surveillance methods that are specific enough to identify organ injury in real time. With this in mind, we propose a pilot study protocol utilizing both donor derived cell free DNA (dd-cfDNA, gene expression profiling (GEP), and machine learning (iBox), called KidneyCare, to assess the feasibility and safety in reducing immunosuppressant exposure without increasing the risk of clinical rejection, graft injury, or allograft loss. Patients randomized to the immunominimization arm will be enrolled in one of two protocols designed to eliminate one immunosuppressant and optimize the dose of the Calcineurin Inhibitors (CNIs) using the KidneyCare platform. All patients will be maintained on dual therapy of either steroids and a low dose CNI, or mycophenolate mofetil (MMF) and low dose CNI. Their outcomes will be compared to patients who have their immunosuppressants managed using standard clinical assessment and treatment protocols to determine the impact of immuno-optimization on graft function, complications, and patient reported outcomes.
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Affiliation(s)
- Jennifer N. Gray
- CareDx, 3260 Bayshore Blvd, Brisbane, CA 94005, USA; (T.W.-D.); (N.S.)
| | - Theresa Wolf-Doty
- CareDx, 3260 Bayshore Blvd, Brisbane, CA 94005, USA; (T.W.-D.); (N.S.)
| | - Nimisha Sulejmani
- CareDx, 3260 Bayshore Blvd, Brisbane, CA 94005, USA; (T.W.-D.); (N.S.)
| | - Osama Gaber
- Houston Methodist Hospital, 6565 Fannin St. Houston, TX 77030, USA;
| | - David Axelrod
- Department of Surgery, University of Iowa Medical Center, 200 Hawkins Dr, Iowa City, IA 52242, USA;
| | - Basmah Abdalla
- UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA 90095, USA; (B.A.); (G.D.)
| | - Gabriel Danovitch
- UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA 90095, USA; (B.A.); (G.D.)
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Zielińska K, Kukulski L, Wróbel M, Przybyłowski P, Zakliczyński M, Strojek K. Prevalence and Risk Factors of New-Onset Diabetes After Transplantation (NODAT). Ann Transplant 2020; 25:e926556. [PMID: 32839423 PMCID: PMC7852038 DOI: 10.12659/aot.926556] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients. The identification of high-risk patients and the implementation of measures to limit the development of NODAT can improve the long-term patient prognosis. Material/Methods Our study group consisted of 336 patients undergoing heart transplant. Patients with prior diabetes (60 patients) were excluded from analysis. The remaining 276 patients were divided in 2 groups: with NODAT (n=109) and without NODAT (n=167). Logistic regression analysis was used for NODAT risk factor assessment. Results NODAT occurred in 109 (32%) out of 336 patients without diagnosed diabetes before heart transplantation. Risk factors for post-transplant diabetes mellitus, which was shown by the analysis of the collected data, were BMI at discharge (OR=1.082, CI 1.011–1.158, p=0.0233), history of diagnosed CMV infection (OR=1.464, CI 1.068–2.007, p=0.0179), and age over 51 years (OR=1.634, CI 1.274–2.095, p=0.0001). Conclusions 1. New-onset diabetes after transplantation (NODAT) or long-lasting hypoglycemia (over 2 years after transplantation) was diagnosed in 32% patients after heart transplantation developed. 2. The risk factors of NODAT were BMI at discharge and history of diagnosed CMV infection, and age over 51 years was an independent risk factor.
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Affiliation(s)
- Katarzyna Zielińska
- Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Leszek Kukulski
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Marta Wróbel
- Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Piotr Przybyłowski
- Department of Cardiac Transplantation and Mechanical Circulatory Support, Silesian Center for Heart Diseases, Zabrze, Poland.,First Chair of General Surgery, Jagiellonian University Medical College, Cracow, Poland
| | - Michał Zakliczyński
- Clinic of Cardiac Transplantation and Mechanical Circulatory Support, Wrocław Medical University, Wrocław, Poland
| | - Krzysztof Strojek
- Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland
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van der Burgh AC, Moes A, Kieboom BCT, van Gelder T, Zietse R, van Schaik RHN, Hesselink DA, Hoorn EJ. Serum magnesium, hepatocyte nuclear factor 1β genotype and post-transplant diabetes mellitus: a prospective study. Nephrol Dial Transplant 2020; 35:176-183. [PMID: 31361318 DOI: 10.1093/ndt/gfz145] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 06/12/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Retrospective studies suggest that tacrolimus-induced hypomagnesaemia is a risk factor for post-transplant diabetes mellitus (PTDM), but prospective studies are lacking. METHODS This was a prospective study with measurements of serum magnesium and tacrolimus at pre-specified time points in the first year after living donor kidney transplantation (KT). The role of single nucleotide polymorphisms (SNPs) in hepatocyte nuclear factor 1β (HNF1β) was also explored because HNF1β regulates insulin secretion and renal magnesium handling. Repeated measurement and regression analyses were used to analyse associations with PTDM. RESULTS In our cohort, 29 out of 167 kidney transplant recipients developed PTDM after 1 year (17%). Higher tacrolimus concentrations were significantly associated with lower serum magnesium and increased risk of hypomagnesaemia. Patients who developed PTDM had a significantly lower serum magnesium trajectory than patients who did not develop PTDM. In multivariate analysis, lower serum magnesium, age and body mass index were independent risk factors for PTDM. In recipients, the HNF1β SNP rs752010 G > A significantly increased the risk of PTDM [odds ratio (OR) = 2.56, 95% confidence interval (CI) 1.05-6.23] but not of hypomagnesaemia. This association lost significance after correction for age and sex (OR = 2.24, 95% CI 0.90-5.57). No association between HNF1β SNPs and PTDM was found in corresponding donors. CONCLUSIONS A lower serum magnesium in the first year after KT is an independent risk factor for PTDM. The HNF1β SNP rs752010 G > A may add to this risk through an effect on insulin secretion rather than hypomagnesaemia, but its role requires further confirmation.
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Affiliation(s)
- Anna C van der Burgh
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Arthur Moes
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Brenda C T Kieboom
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Teun van Gelder
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Robert Zietse
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ron H N van Schaik
- Department of Clinical Chemistry, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Dennis A Hesselink
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ewout J Hoorn
- Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erectile Dysfunction after Kidney Transplantation. J Clin Med 2020; 9:jcm9061991. [PMID: 32630390 PMCID: PMC7356955 DOI: 10.3390/jcm9061991] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/12/2020] [Accepted: 06/22/2020] [Indexed: 12/15/2022] Open
Abstract
Patients with kidney transplantation often have a worse quality of life than the general population. One of the reasons for this, in male patients, is the high prevalence of erectile dysfunction. This is mainly due to the presence of comorbidities, surgery for kidney transplantation, adverse drug effects, psychological changes related to chronic disease, as well as hyperprolactinemia and hypogonadism. Whenever these endocrine dysfunctions occur after kidney transplantation, they must be corrected with appropriate treatment, i.e., testosterone replacement therapy. Administration of the phosphodiesterase-5 inhibitor (PDE5i) sildenafil at the recommended posology does not significantly alter the pharmacokinetics of the calcineurin inhibitors cyclosporin A or tacrolimus and does not impair kidney allograft function. Tacrolimus increases the peak concentration and prolongs the half-life of PDE5i in kidney transplant patients and, therefore, daily administration cannot be recommended due to the significant drop in blood pressure. Intracavernous injection or topical application of alprostadil can be a second-line option for the treatment of erectile dysfunction after kidney transplantation, which does not alter cyclosporine concentrations and does not deteriorate kidney function. Finally, penile prostheses can be successfully implanted following pelvic organ transplantation after eliminating the risk of infection associated with surgery.
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Cohen E, Korah M, Callender G, Belfort de Aguiar R, Haakinson D. Metabolic Disorders with Kidney Transplant. Clin J Am Soc Nephrol 2020; 15:732-742. [PMID: 32284323 PMCID: PMC7269213 DOI: 10.2215/cjn.09310819] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient's ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%-30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.
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Affiliation(s)
- Elizabeth Cohen
- Department of Pharmacy, Yale-New Haven Hospital, New Haven, Connecticut
| | - Maria Korah
- Yale University School of Medicine, New Haven, Connecticut
| | - Glenda Callender
- Department of Surgery, Section of Endocrine Surgery, Yale University, New Haven, Connecticut
| | | | - Danielle Haakinson
- Department of Surgery, Section of Transplant, Yale University, New Haven, Connecticut
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Osté MCJ, Flores-Guerrero JL, Gruppen EG, Kieneker LM, Connelly MA, Otvos JD, Dullaart RPF, Bakker SJL. High Plasma Branched-Chain Amino Acids Are Associated with Higher Risk of Post-Transplant Diabetes Mellitus in Renal Transplant Recipients. J Clin Med 2020; 9:jcm9020511. [PMID: 32069900 PMCID: PMC7073569 DOI: 10.3390/jcm9020511] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 02/11/2020] [Indexed: 01/21/2023] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a functioning graft for ≥1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 ± 13.6 y (53.6% men) and plasma BCAA was 377.6 ± 82.5 µM. During median follow-up of 5.3 (IQR, 4.2–6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08–1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c < 5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM.
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Affiliation(s)
- Maryse C. J. Osté
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (L.M.K.); (S.J.L.B.)
- Correspondence: ; Tel.: +31-50-371-3449
| | - Jose L. Flores-Guerrero
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (L.M.K.); (S.J.L.B.)
| | - Eke G. Gruppen
- Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (E.G.G.); (R.P.F.D.)
| | - Lyanne M. Kieneker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (L.M.K.); (S.J.L.B.)
| | - Margery A. Connelly
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (M.A.C.); (J.D.O.)
| | - James D. Otvos
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (M.A.C.); (J.D.O.)
| | - Robin P. F. Dullaart
- Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (E.G.G.); (R.P.F.D.)
| | - Stephan J. L. Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (L.M.K.); (S.J.L.B.)
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Munshi VN, Saghafian S, Cook CB, Eric Steidley D, Hardaway B, Chakkera HA. Incidence, Risk Factors, and Trends for Postheart Transplantation Diabetes Mellitus. Am J Cardiol 2020; 125:436-440. [PMID: 31812226 DOI: 10.1016/j.amjcard.2019.10.054] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/25/2019] [Accepted: 10/30/2019] [Indexed: 01/12/2023]
Abstract
This retrospective study analyzed glycemic trends, incidence of post-transplant diabetes mellitus (PTDM) incidence and associated risk factors in a cohort of patients who underwent first-time heart transplantation (HT). Univariate analyses compared patient with and without pretransplant diabetes mellitus (DM). Multivariate regression analyses were conducted to determine association between PTDM and different risk factors. Finally, trends in glucometrics and other outcomes are described across follow-up time points. There were 152 patients who underwent HT between 2010 and 2015, 109 of whom had no pretransplant history of DM. PTDM incidence was 38% by the 1-year follow-up. Pretransplant body mass index (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.23, p = 0.03), insulin use during the final 24 hours of inpatient stay (OR 4.26, 95% CI 1.72 to 10.56, p <0.01), mean inpatient glucose (OR 2.21, 95% CI 1.33 to 3.69, p <0.01), and mean glucose in the final 24 hours before discharge (OR 1.29, 95% CI 1.03 to 1.60, p = 0.03) were associated with increased odds of PTDM at 1 year. In patients on insulin before discharge, blood glucose values were significantly higher compared with those who were not (136 mg/dl vs 114 mg/dl at 1 to 3 months, 112 vs 100 at 4 to 6 months, 109 vs 98 at 8 to 12 months, all p <0.01). This analysis improves understanding of PTDM incidence, glucometric trends, and risk differences by DM status in the HT population. Similar to liver and kidney patients, inpatient glucometrics may be informative of PTDM risk in HT patients. Guidelines for this population should be developed to account for risk heterogeneity and need for differential management.
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Munshi VN, Saghafian S, Cook CB, Werner KT, Chakkera HA. Comparison of post-transplantation diabetes mellitus incidence and risk factors between kidney and liver transplantation patients. PLoS One 2020; 15:e0226873. [PMID: 31923179 PMCID: PMC6953760 DOI: 10.1371/journal.pone.0226873] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 12/06/2019] [Indexed: 12/13/2022] Open
Abstract
Background Most prior studies characterizing post-transplantation diabetes mellitus (PTDM) have been limited to single-cohort, single-organ studies. This retrospective study determined PTDM across organs by comparing incidence and risk factors among 346 liver and 407 kidney transplant recipients from a single center. Methods Univariate and multivariate regression-based analyses were conducted to determine association of various risk factors and PTDM in the two cohorts, as well as differences in glucometrics and insulin use across time points. Results There was a higher incidence of PTDM among liver versus kidney transplant recipients (30% vs. 19%) at 1-year post-transplant. Liver transplant recipients demonstrated a 337% higher odds association to PTDM (OR 3.37, 95% CI (1.38–8.25), p<0.01). 1-month FBG was higher in kidney patients (135 mg/dL vs 104 mg/dL; p < .01), while 1-month insulin use was higher in liver patients (61% vs 27%, p < .01). Age, BMI, insulin use, and inpatient FBG were also significantly associated with differential PTDM risk. Conclusions Kidney and liver transplant patients have different PTDM risk profiles, both in terms of absolute PTDM risk as well as time course of risk. Management of this population should better reflect risk heterogeneity to short-term need for insulin therapy and potentially long-term outcomes.
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Affiliation(s)
- Vidit N. Munshi
- PhD Program in Health Policy, Harvard University, Cambridge, Massachusetts, United States of America
- * E-mail:
| | - Soroush Saghafian
- Harvard Kennedy School, Harvard University, Cambridge, Massachusetts, United States of America
| | - Curtiss B. Cook
- Mayo Clinic Arizona, Scottsdale, Arizona, United States of America
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Guzmán GE, Victoria AM, Ramos I, Maldonado A, Manzi E, Contreras-Valero JF, Mesa L, Schweineberg J, Posada JG, Villegas JI, Caicedo LA, Durán CE. Risk Factors Related to New-Onset Diabetes after Renal Transplantation in Patients of a High Complexity University Hospital in Colombia, 20 Years of Experience. Int J Endocrinol 2020; 2020:8297192. [PMID: 32908503 PMCID: PMC7477588 DOI: 10.1155/2020/8297192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 07/13/2020] [Accepted: 08/01/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION New-onset diabetes after transplantation (NODAT) is associated with immunosuppression. Its complications can negatively influence patients' quality of life, which is why it is important to study the associated risk factors and expand the possible therapies in this particular group of patients. Materials and methods. Case-control study nested in a retrospective cohort. It included patients who received kidney transplantation at the high complexity University Hospital Fundación Valle del Lili in Cali, Colombia, between 1995 and 2014. Two controls were assigned for each case, depending on the type of donor and the date of the surgery. Information was collected from clinical records and the institutional TRENAL registry. We carried out a descriptive analysis of the selected variables and identified the risk factors with conditional logistic regression. RESULTS 122 cases were identified to which 224 controls were assigned. The median age was 44 years (IQR: 34-55), and 54% were men. Having >50 years of age at the time of transplantation (OR: 3.18, 95% CI: 1.6-6.3, p = 0.001), body mass index >30 kg/m2 (OR: 3.6, 95% CI: 1.3-9.7, p = 0.010) and being afro-descendant (OR: 2.74, 95% CI: 1.1-6.5, p = 0.023) were identified as risk factors for the development of NODAT. Pretransplant fasting plasma glucose >100 mg/dl (OR: 2.9, 95% CI: 1.4-6.4, p = 0.005) and serum triglycerides >200 mg/dl (OR: 2.5, 95% CI: 1.4-4.4, p = 0.002) were also reported as independent risk factors. CONCLUSION We ratify some risk factors for the development of this important disease, which include certain modifiable characteristics. Interventions aimed at changes in lifestyle could be established in a timely manner before transplant surgery.
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Affiliation(s)
- Guillermo E. Guzmán
- Fundación Valle del Lili, Departamento de Endocrinología, Cra 98, No. 18-49, Cali 760032, Colombia
- Universidad Icesi, Facultad de Ciencias de la Salud, Calle 18, No. 122-135, Cali, Colombia
| | - Angela M. Victoria
- Universidad Icesi, Facultad de Ciencias de la Salud, Calle 18, No. 122-135, Cali, Colombia
| | - Isabella Ramos
- Universidad Icesi, Facultad de Ciencias de la Salud, Calle 18, No. 122-135, Cali, Colombia
| | - Alejandro Maldonado
- Universidad Icesi, Facultad de Ciencias de la Salud, Calle 18, No. 122-135, Cali, Colombia
| | - Eliana Manzi
- Fundación Valle del Lili, Centro de Investigaciones Clínicas, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Juan F. Contreras-Valero
- Universidad Icesi, Facultad de Ciencias de la Salud, Calle 18, No. 122-135, Cali, Colombia
- Fundación Valle del Lili, Departamento de Medicina Interna, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Liliana Mesa
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Johanna Schweineberg
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Juan G. Posada
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Jorge I. Villegas
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Luis A. Caicedo
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
| | - Carlos E. Durán
- Fundación Valle del Lili, Departamento de Nefrología–Unidad de Trasplantes, Cra 98, No. 18-49, Cali 760032, Colombia
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Alamdari A, Asadi G, Minoo FS, Khatami MR, Gatmiri SM, Dashti-Khavidaki S, Heydari Seradj S, Naderi N. Association Between Pre-Transplant Magnesemia and Post-Transplant Dysglycemia in Kidney Transplant Recipients. Int J Endocrinol Metab 2020; 18:e97292. [PMID: 32308698 PMCID: PMC7138613 DOI: 10.5812/ijem.97292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 12/09/2019] [Accepted: 12/17/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Serum magnesium (Mg) status in kidney transplant recipients has been a center of attention in the past few years. Current evidence suggests an association between pre-transplant hypomagnesemia and post-transplant hyperglycemia. OBJECTIVE The purpose of this study was to assess the associations of pre-transplant magnesemia with blood glucose disturbances within 6 months post-kidney transplantation. METHODS In this retrospective cohort, 89 first-time kidney transplant recipients with 6 months of follow-up were included. None of the participants had a positive history of rejection, pre-transplant history of diabetes mellitus or fasting plasma glucose ≥ 100 mg/dL. RESULTS Post-transplant diabetes mellitus (PTDM) and impaired fasting glucose (IFG) 6 months post-transplant was found in 7.9% and 41.6% of the study group, respectively. The mean pre-transplant serum Mg level was 1.92 ± 0.30 mg/dL in the study population (n = 89), and it was significantly lower in IFG (n = 37) and IFG/PTDM (n = 44) groups compared to normoglycemic (n = 45) recipients (1.83 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.008, and 1.84 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.012, respectively). Patients with serum Mg less than 1.9 mg/dL were nearly 2.6 times more likely to develop IFG or IFG/PTDM within 6 months post-transplant (P = 0.044 and P = 0.040, respectively). CONCLUSIONS Pre-transplant hypomagnesemia may be considered a risk factor for developing post-transplant glycemic disturbances, and patients with lower pre-transplant Mg concentration could be at a higher risk for developing IFG.
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Affiliation(s)
- Azam Alamdari
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazal Asadi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzaneh Sadat Minoo
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad-Reza Khatami
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mansour Gatmiri
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
| | - Simin Dashti-Khavidaki
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Neda Naderi
- Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
- Corresponding Author: Nephrology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters. Transplant Direct 2019; 6:e517. [PMID: 32047845 PMCID: PMC6964931 DOI: 10.1097/txd.0000000000000964] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 11/03/2019] [Accepted: 11/10/2019] [Indexed: 12/13/2022] Open
Abstract
Background. Calcineurin inhibitors (CNIs) and steroids are strongly associated with new-onset diabetes after transplantation, worsening of pre-existing diabetes, and cardiovascular events. We assessed the benefit of conversion from CNI-based to belatacept-based immunosuppression in diabetic kidney-transplant (KT) recipients on glucose control and cardiovascular risk factors. Methods. In this retrospective, noncontrolled single-study conducted between May 2016 and October 26, 2018, we recruited KT recipients converted from CNIs to belatacept at least 6 months after KT. The primary endpoint was the evolution of hemoglobin A1c (HbA1c) between baseline and after 6 months of treatment. Secondary endpoints included modifications to antidiabetic drugs, other cardiovascular risk factors, and renal function. Results. One hundred and three KT recipients were included. Of these, 26 (25%) had type 2 diabetes. The patients were either receiving oral antidiabetic drugs (n = 21; 75%) or insulin therapy (n = 14; 54%). Overall HbA1c decreased significantly from 6.2 ± 1 to 5.8 ± 1%, P < 0.001. In diabetic patients, HbA1c decreased from 7.2 ± 1 to 6.5 ± 1%, P = 0.001. HbA1c significantly decreased in the subgroup of patients with new-onset diabetes after transplantation and whether diabetes was controlled at inclusion or not (ie, HA1c ≤7% or >7%). Moreover, no diabetic patient increased the number of oral antidiabetic drugs and the dose of basal insulin was not statistically different from baseline to 6 months (16 international unit at baseline and 16 international unit at 6 mo, P = 1). One patient had to start treatment by insulin pump. During follow-up, the renal function, body mass index, and hemoglobin level of all 103 patients remained stable, 2 patients presented acute cellular rejection, and no patient suffered from graft loss. Conclusions. A late switch from CNI to belatacept was a valuable therapeutic option for diabetic kidney recipients and substantially improved glycemic parameters.
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Validation of Identified Susceptible Gene Variants for New-Onset Diabetes in Renal Transplant Recipients. J Clin Med 2019; 8:jcm8101696. [PMID: 31623129 PMCID: PMC6832625 DOI: 10.3390/jcm8101696] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 10/03/2019] [Accepted: 10/12/2019] [Indexed: 12/19/2022] Open
Abstract
Genome-wide association studies (GWAS) and candidate gene approaches have identified single nucleotide polymorphisms (SNPs) associated with new-onset diabetes after renal transplantation (NODAT). We evaluated associations between NODAT and SNPs identified in previous studies. We genotyped 1102 renal transplant recipients from the Korean Organ Transplantation Registry (KOTRY) database; 13 SNPs were assessed for associations with NODAT (occurring in 254 patients; 23.0%), within one year after transplantation. The frequency of the T allele at KCNQ1 rs2237892 was significantly lower in patients with NODAT compared to control patients (0.30 vs. 0.39; p = 8.5 × 10-5). The T allele at rs2237892 was significantly associated with decreased risk of NODAT after adjusting for multiple variables, compared to the C allele (OR 0.63, 95% CI 0.51-0.79; p = 5.5 × 10-5). Dominant inheritance modeling showed that CT/TT genotypes were associated with a lower risk for development of NODAT (OR 0.56, 95% CI 0.42-0.76; p = 2.0 × 10-4) compared to the CC genotype. No other SNPs were associated with NODAT. Our study validated the protective effect of T allele at KCNQ1 rs2237892 on the development of NODAT in a large cohort of renal transplant recipients. Our findings on susceptibility variants might be a useful tool to predict NODAT development after renal transplantation.
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Devine PA, Courtney AE, Maxwell AP. Cardiovascular risk in renal transplant recipients. J Nephrol 2019; 32:389-399. [PMID: 30406606 PMCID: PMC6482292 DOI: 10.1007/s40620-018-0549-4] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/30/2018] [Indexed: 02/07/2023]
Abstract
Successful kidney transplantation offers patients with end-stage renal disease the greatest likelihood of survival. However, cardiovascular disease poses a major threat to both graft and patient survival in this cohort. Transplant recipients are unique in their accumulation of a wide range of traditional and non-traditional cardiovascular risk factors. Hypertension, diabetes, dyslipidaemia and obesity are highly prevalent in patients with end-stage renal disease. These risk factors persist following transplantation and are often exacerbated by the drugs used for immunosuppression in organ transplantation. Additional transplant-specific factors such as poor graft function and proteinuria are also associated with increased cardiovascular risk. However, these transplant-related factors remain unaccounted for in current cardiovascular risk prediction models, making it challenging to identify transplant recipients with highest risk. With few interventional trials in this area specific to transplant recipients, strategies to reduce cardiovascular risk are largely extrapolated from other populations. Aggressive management of traditional cardiovascular risk factors remains the cornerstone of prevention, though there is also a potential role for selecting immunosuppression regimens to minimise additional cardiovascular injury.
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Affiliation(s)
- Paul A Devine
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK.
- Centre for Public Health, Queen's University Belfast, Belfast, UK.
| | - Aisling E Courtney
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK
| | - Alexander P Maxwell
- Regional Nephrology and Transplant Unit, Belfast City Hospital Northern Ireland, Belfast, BT9 7AB, UK
- Centre for Public Health, Queen's University Belfast, Belfast, UK
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Alnasrallah B, Goh TL, Chan LW, Manley P, Pilmore H. Transplantation and diabetes (Transdiab): a pilot randomised controlled trial of metformin in impaired glucose tolerance after kidney transplantation. BMC Nephrol 2019; 20:147. [PMID: 31035960 PMCID: PMC6489311 DOI: 10.1186/s12882-019-1321-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 03/31/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Post transplantation diabetes mellitus (PTDM) is a common and serious complication after renal transplantation with significant morbidity and mortality. Metformin has proven benefits in the general population and might be advantageous in the prevention and management of PTDM. METHODS Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants had an oral glucose tolerance test (OGTT) in the 4-12 weeks post-transplantation; those with IGT were randomised to standard care or standard care and metformin 500 mg twice daily and followed up for 12 months. RESULTS Seventy eight patients had an OGTT over 24 months, 25 of them had IGT, of those, 19 patients were randomised, giving a feasibility of recruitment of 24.4%. Ten patients were randomised to metformin and 9 patients to standard care. Tolerability and efficacy was similar between the 2 groups with no serious adverse events. There was no difference in secondary outcomes relating to the metabolic profile. CONCLUSIONS The use of metformin post renal transplantation appeared feasible and safe. Larger randomised controlled trials (RCTs) are needed to establish and confirm the efficacy and safety of metformin post renal transplantation. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12614001171606 . Date of registration 7/11/2014.
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Affiliation(s)
- Basil Alnasrallah
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand.
| | - Tze Liang Goh
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Lai Wan Chan
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Paul Manley
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Helen Pilmore
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand.,Department of Medicine, University of Auckland, Auckland, New Zealand
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Yepes-Calderón M, Sotomayor CG, Gomes-Neto AW, Gans ROB, Berger SP, Rimbach G, Esatbeyoglu T, Rodrigo R, Geleijnse JM, Navis GJ, Bakker SJL. Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study. J Clin Med 2019; 8:453. [PMID: 30987358 PMCID: PMC6518172 DOI: 10.3390/jcm8040453] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 03/29/2019] [Accepted: 03/30/2019] [Indexed: 12/14/2022] Open
Abstract
New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92-3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6-6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36-0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.
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Affiliation(s)
- Manuela Yepes-Calderón
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Camilo G Sotomayor
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - António W Gomes-Neto
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Rijk O B Gans
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Stefan P Berger
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Herrmann Rodewaldstrasse 6, D-24118 Kiel, Germany.
| | - Tuba Esatbeyoglu
- Institute of Food Science and Human Nutrition, Department Food Development and Food Quality, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, D-30167 Hannover, Germany.
| | - Ramón Rodrigo
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, CP 8380453 Santiago, Chile.
| | - Johanna M Geleijnse
- Division of Human Nutrition and Health, Wageningen University and Research, P.O. Box 47, 6700 AA Wageningen, The Netherlands.
| | - Gerjan J Navis
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Stephan J L Bakker
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
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Noble J, Jouve T, Janbon B, Rostaing L, Malvezzi P. Belatacept in kidney transplantation and its limitations. Expert Rev Clin Immunol 2019; 15:359-367. [DOI: 10.1080/1744666x.2019.1574570] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Johan Noble
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Thomas Jouve
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Bénédicte Janbon
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
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Eisenga MF, Gomes-Neto AW, van Londen M, Ziengs AL, Douwes RM, Stam SP, Osté MCJ, Knobbe TJ, Hessels NR, Buunk AM, Annema C, Siebelink MJ, Racz E, Spikman JM, Bodewes FAJA, Pol RA, Berger SP, Drost G, Porte RJ, Leuvenink HGD, Damman K, Verschuuren EAM, de Meijer VE, Blokzijl H, Bakker SJL. Rationale and design of TransplantLines: a prospective cohort study and biobank of solid organ transplant recipients. BMJ Open 2018; 8:e024502. [PMID: 30598488 PMCID: PMC6318532 DOI: 10.1136/bmjopen-2018-024502] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION In the past decades, short-term results after solid organ transplantation have markedly improved. Disappointingly, this has not been accompanied by parallel improvements in long-term outcomes after transplantation. To improve graft and recipient outcomes, identification of potentially modifiable risk factors and development of biomarkers are required. We provide the rationale and design of a large prospective cohort study of solid organ transplant recipients (TransplantLines). METHODS AND ANALYSIS TransplantLines is designed as a single-centre, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. Data will be collected from transplant candidates before transplantation, during transplantation, at 3 months, 6 months, 1 year, 2 years and 5 years, and subsequently every 5 years after transplantation. Data from living organ donors will be collected before donation, during donation, at 3 months, 1 year and 5 years after donation, and subsequently every 5 years. The primary outcomes are mortality and graft failure. The secondary outcomes will be cause-specific mortality, cause-specific graft failure and rejection. The tertiary outcomes will be other health problems, including diabetes, obesity, hypertension, hypercholesterolaemia and cardiovascular disease, and disturbances that relate to quality of life, that is, physical and psychological functioning, including quality of sleep, and neurological problems such as tremor and polyneuropathy. ETHICS AND DISSEMINATION Ethical approval has been obtained from the relevant local ethics committee. The TransplantLines cohort study is designed to deliver pioneering insights into transplantation and donation outcomes. The study design allows comprehensive data collection on perioperative care, nutrition, social and psychological functioning, and biochemical parameters. This may provide a rationale for future intervention strategies to more individualised, patient-centred transplant care and individualisation of treatment. TRIAL REGISTRATION NUMBER NCT03272841.
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Affiliation(s)
- Michele F Eisenga
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Antonio W Gomes-Neto
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marco van Londen
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Aaltje L Ziengs
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Neuropsychology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Rianne M Douwes
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Suzanne P Stam
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maryse C J Osté
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Tim J Knobbe
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Niek R Hessels
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Anne M Buunk
- Department of Neuropsychology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Coby Annema
- Groningen Transplant Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marion J Siebelink
- Groningen Transplant Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Emoke Racz
- Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jacoba M Spikman
- Department of Neuropsychology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Frank A J A Bodewes
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert A Pol
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Stefan P Berger
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Gea Drost
- Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J Porte
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Henri G D Leuvenink
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Kevin Damman
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Erik A M Verschuuren
- Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Stephan J L Bakker
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Santos AH, Chen C, Casey MJ, Womer KL, Wen X. New-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology? Nephrol Dial Transplant 2018; 33:177-184. [PMID: 29045704 DOI: 10.1093/ndt/gfx281] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Indexed: 12/14/2022] Open
Abstract
Background This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac]. Methods Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis. Results Adult KTRs (n = 97 644) from January 1995 through September 2015 were studied. HCV+ [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.31-1.68] or CMV+ (HR 1.12, 95% CI 1.06-1.19) serology was a risk factor and HBc+ (HR 1.04, 95% CI 0.95-1.15) or EBV+ (HR 1.06, 95% CI 0.97-1.15) serology was not a risk factor for NODAT. Regardless of associated HCV or CMV serology, risk of NODAT relative to the reference regimen (Tac + MPA) was lower with CSA + MPA [HCV-: HR 0.74, 95% CI 0.65-0.85; HCV+: HR 0.47, 95% CI 0.28-0.78; CMV-: CSA + MPA HR 0.68, 95% CI 0.54-0.86; CMV+: (CSA + MPA) HR 0.73, 95% CI 0.63-0.85] and similar with SRL + CSA or SRL + MPA. In KTRs with HCV- or CMV+ serology, SRL + Tac was associated with a higher risk of NODAT relative to reference [HCV- (HR 1.43, 95% CI 1.17-1.74) and CMV+ (HR 1.44, 95% CI 1.14-1.81), respectively]. The risk for NODAT-free graft loss was lower with Tac + MPA than the other regimens. Conclusions Tailoring immunosuppression regimen based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.
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Affiliation(s)
- Alfonso H Santos
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Chao Chen
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Michael J Casey
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Karl L Womer
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Xuerong Wen
- Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
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Abstract
PURPOSE OF REVIEW The leading cause of death in both chronic kidney disease (CKD) and renal transplant patients is cardiovascular events. Post-transplant diabetes mellitus (PTx-DM), which is a major cardiovascular risk factor, is a metabolic disorder that affects 5.5-60.2% of renal allograft recipients by 1-year posttransplant (PTx). PTx-DM has been associated with a negative impact on patient and graft outcomes and survival. RECENT FINDINGS Individuals who develop PTx-DM are usually prone to this condition prior to and/or after developing CKD. Genetic factors, obesity, inflammation, medications and CKD all are risk factors for PTx-diabetes mellitus. The path to development of disease continues PTx frequently augmented by the use of diabetogenic maintenance immunosuppressive and some nonimmunosuppressive medications. These risk factors are usually associated with an increase in insulin resistance, a decrease in insulin gene expression and/or β-cell dysfunction and apoptosis. SUMMARY Some new anti-diabetes mellitus medications may help to improve the overall outcome; however, there is a real need for developing a preventive strategy. Identifying and targeting PTx-DM risk factors may help to guide the development of an effective programme. This could include the adoption of nondiabetogenic immunosuppressive protocols for high-risk patients.
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Li ZJ, Du LF, Qin Y, Liu JB, Luo XH. Ultrasound Assessment of Intima-media Thickness and Diameter of Carotid Arteries in Patients Undergoing Hemodialysis or Renal Transplantation. Curr Med Sci 2018; 38:727-733. [PMID: 30128885 DOI: 10.1007/s11596-018-1937-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 04/10/2018] [Indexed: 11/25/2022]
Abstract
Renal transplant (RT) recipients have a high risk of developing cardiovascular diseases. However, the effects of renal transplantation on the development of arteriosclerosis have been controversial. The carotid intima-media thickness (СШТ) and diameter (CD) are important indicators of vascular remodeling and arteriosclerosis. In this study, 31 patients with hemodialysis (HD), 31 RT recipients and 84 age- and gender-matched control subjects were enrolled. Their CIMT and CD were measured by ultrasonic radiofrequency tracking, and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors. Compared with HD group, RT group had significantly lower CIMT and CD. CIMT was found to be associated with age, body weight, resistance index and diastolic velocity, while CD was associated significantly with age, body weight, pulsatility index, end diastolic velocity and diastolic blood pressure (DBP), respectively. The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control, RT and HD groups, and the curves between CD and age showed the slopes were decreased in order of RT > control > HD groups. It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients. RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.
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Affiliation(s)
- Zhao-Jun Li
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
| | - Lian-Fang Du
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
| | - Yan Qin
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University, Philadelphia, 19107, USA.
| | - Xiang-Hong Luo
- Department of Echocardiography, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China.
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