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Dziedziejko V, Safranow K, Kijko-Nowak M, Malinowski D, Domanski L, Pawlik A. Leptin receptor gene polymorphisms in kidney transplant patients with post-transplant diabetes mellitus treated with tacrolimus. Int Immunopharmacol 2023; 124:110989. [PMID: 37776770 DOI: 10.1016/j.intimp.2023.110989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 08/17/2023] [Accepted: 09/22/2023] [Indexed: 10/02/2023]
Abstract
Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development.
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Affiliation(s)
- Violetta Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Mirosława Kijko-Nowak
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Damian Malinowski
- Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Leszek Domanski
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland.
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2
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Singer J, Aouad LJ, Wyburn K, Gracey DM, Ying T, Chadban SJ. The Utility of Pre- and Post-Transplant Oral Glucose Tolerance Tests: Identifying Kidney Transplant Recipients With or at Risk of New Onset Diabetes After Transplant. Transpl Int 2022; 35:10078. [PMID: 35368638 PMCID: PMC8967957 DOI: 10.3389/ti.2022.10078] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/24/2022] [Indexed: 11/13/2022]
Abstract
Background: New onset diabetes after transplant (NODAT) is common in kidney transplant recipients (KTRs). Identifying patients at risk prior to transplant may enable strategies to mitigate NODAT, with a pre-transplant oral glucose tolerance test (OGTT) suggested by the KDIGO 2020 Guidelines for this purpose. Methods: We investigated the utility of pre- and post-transplant OGTTs to stratify risk and diagnose NODAT in a retrospective, single-centre cohort study of all non-diabetic KTRs transplanted between 2003 and 2018. Results: We identified 597 KTRs who performed a pre-transplant OGTT, of which 441 had their post-transplant glycaemic status determined by a clinical diagnosis of NODAT or OGTT. Pre-transplant dysglycaemia was identified in 28% of KTRs and was associated with increasing age (p < 0.001), BMI (p = 0.03), and peritoneal dialysis (p < 0.001). Post-transplant dysglycaemia was common with NODAT and impaired glucose tolerance (IGT) occurring in 143 (32%) and 121 (27%) patients, respectively. Pre-transplant IGT was strongly associated with NODAT development (OR 3.8, p < 0.001). Conclusion: A pre-transplant OGTT identified candidates at increased risk of post-transplant dysglycaemia and NODAT, as diagnosed by an OGTT. Robust prospective trials are needed to determine whether various interventions can reduce post-transplant risk for candidates with an abnormal pre-transplant OGTT.
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Affiliation(s)
- Julian Singer
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Leyla J Aouad
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Kate Wyburn
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - David M Gracey
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Tracey Ying
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Steven J Chadban
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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Ducloux D, Courivaud C. Prevention of Post-Transplant Diabetes Mellitus: Towards a Personalized Approach. J Pers Med 2022; 12:116. [PMID: 35055431 PMCID: PMC8778007 DOI: 10.3390/jpm12010116] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/06/2022] [Accepted: 01/13/2022] [Indexed: 02/01/2023] Open
Abstract
Post-transplant diabetes is a frequent complication after transplantation. Moreover, patients suffering from post-transplant diabetes have increased cardiovascular morbidity and reduced survival. Pathogenesis mainly involves beta-cell dysfunction in presence of insulin resistance. Both pre- and post-transplant risk factors are well-described, and some of them may be corrected or prevented. However, the frequency of post-transplant diabetes has not decreased in recent years. We realized a critical appraisal of preventive measures to reduce post-transplant diabetes.
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Affiliation(s)
- Didier Ducloux
- CHU Besançon, Department of Nephrology, Dialysis and Renal Transplantation, Federation Hospitalo-Universitaire INCREASE, 25000 Besançon, France;
- UMR RIGHT 1098, INSERM-EFS-UFC, 1 Bd Fleming, 25000 Besançon, France
| | - Cécile Courivaud
- CHU Besançon, Department of Nephrology, Dialysis and Renal Transplantation, Federation Hospitalo-Universitaire INCREASE, 25000 Besançon, France;
- UMR RIGHT 1098, INSERM-EFS-UFC, 1 Bd Fleming, 25000 Besançon, France
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4
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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: 9] [Impact Index Per Article: 1.8] [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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Porrini E, Díaz JM, Moreso F, Lauzurrica R, Ibernon M, Torres IS, Ruiz RB, Rodríguez Rodríguez AE, Mallén PD, Bayés-Genís B, Gainza FJ, Osorio JM, Osuna A, Domínguez R, Ruiz JC, Sosa AJ, Rinne AG, Miranda DM, Macías M, Torres A. Prediabetes is a risk factor for cardiovascular disease following renal transplantation. Kidney Int 2019; 96:1374-1380. [PMID: 31611066 DOI: 10.1016/j.kint.2019.06.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/04/2019] [Accepted: 06/27/2019] [Indexed: 12/14/2022]
Abstract
Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.
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Affiliation(s)
- Esteban Porrini
- Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain.
| | | | | | | | | | | | | | | | | | | | | | - José Manuel Osorio
- Nephrology Section, Hospital Nuestra Señora Virgen de las Nieves, Granada, Spain
| | - Antonio Osuna
- Nephrology Section, Hospital Nuestra Señora Virgen de las Nieves, Granada, Spain
| | - Rosa Domínguez
- Nephrology Unit, Hospital Marqués de Valdecilla, Santander, Spain
| | - Juan Carlos Ruiz
- Nephrology Unit, Hospital Marqués de Valdecilla, Santander, Spain
| | | | | | | | - Manuel Macías
- Nephrology Unit, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain
| | - Armando Torres
- Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain; Nephrology Unit, Hospital Universitario de Canarias, La Laguna, Spain
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Dedinská I, Mäčková N, Kantárová D, Kováčiková L, Graňák K, Laca Ľ, Miklušica J, Skálová P, Galajda P, Mokáň M. Leptin - A new marker for development of post-transplant diabetes mellitus? J Diabetes Complications 2018; 32:863-869. [PMID: 30049444 DOI: 10.1016/j.jdiacomp.2018.07.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 06/21/2018] [Accepted: 07/04/2018] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Obese patients have increased leptin production and selective resistance to its central anti-adipogenic effects, yet its pro-inflammatory immunostimulating effects persist. MATERIAL AND METHODS In a group of 70 patients who underwent primary kidney transplantation (KT) we examined adiponectin and leptin levels at the time of KT and 6 months post-transplantation. Patients with diabetes mellitus type 1 or type 2 at the time of KT were excluded from the study. RESULTS We found that leptin levels significantly increased during the post-transplant period (P = 0.0065). Overall, leptin levels were positively correlated with the level of triacylglycerols, post-transplant diabetes mellitus (PTDM) development and acute rejection (AR). We discovered that, in particular, high leptin levels were associated with AR [OR 2.1273; 95% CI 1.0130-4.4671 (P = 0.0461)] and PTDM development [OR 7.200; 95% CI 1.0310-50.2836 (P = 0.0465)], whereas, low adiponectin levels represent a risk factor for the development of insulin resistance [HR 38.6135; 95% CI 13.3844-67.7699 (P < 0.0001)] and obesity [HR 3.0821; 95% CI 0.8700-10.9192 (P = 0.0053)]. CONCLUSION We found that a high serum concentration of leptin before KT is associated with both PTDM development and AR and merits further investigation in relation to KT.
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Affiliation(s)
- Ivana Dedinská
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic.
| | | | | | - Lea Kováčiková
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Karol Graňák
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Ľudovít Laca
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Juraj Miklušica
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Petra Skálová
- Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Peter Galajda
- Ist Department of Internal Diseases, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
| | - Marián Mokáň
- Ist Department of Internal Diseases, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Slovak Republic
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Diabetes Mellitus Following Renal Transplantation: Clinical and Pharmacological Considerations for the Elderly Patient. Drugs Aging 2017; 34:589-601. [PMID: 28718072 DOI: 10.1007/s40266-017-0478-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Post-transplant diabetes mellitus occurs in 30-50% of cases during the first year post-renal transplantation. It is associated with increased morbidity, mortality and healthcare costs. Risk factors include age and specific immunosuppression regimens. At the same time, renal transplantation is increasingly indicated in elderly (aged >65 years) patients as this proportion of older patients in the prevalent dialysis population has increased. The immune system and β cells undergo senescence and this impacts on the risk for developing post-transplant diabetes and our ability to prevent such development. It may, however, be possible to identify patients at risk of developing post-transplant diabetes, enabling treatment protocols that prevent or reduce the impact of post-transplant diabetes. Much work remains to be completed in this area and is facilitated by the growing base of knowledge regarding the pathophysiology of post-transplant diabetes. Should post-transplant diabetes develop, there are a range of treatment options available. There is increasing interest in using newer agents, although their safety and efficacy in transplant recipients remains to be conclusively established.
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A Prospective Study of Renal Transplant Recipients: A Fall in Insulin Secretion Underpins Dysglycemia After Renal Transplantation. Transplant Direct 2016; 2:e107. [PMID: 27826600 PMCID: PMC5096434 DOI: 10.1097/txd.0000000000000618] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023] Open
Abstract
Background Dysglycemia (encompassing impaired glucose tolerance and diabetes mellitus) arising after renal transplantation is common and confers a significant cardiovascular mortality risk. Nonetheless, the pathophysiology of posttransplant dysglycemia is not well described. The aim of this study was to prospectively and comprehensively assess glucose handling in renal transplant recipients from before to 12 months after transplantation to determine the underpinning pathophysiology. Materials and Methods Intravenous and oral glucose tolerance testing was conducted before and at 3 and 12 months posttransplantation. An intravenous glucose tolerance test was also performed on day 7 posttransplantation. We followed up 16 transplant recipients for 3 months and 14 recipients for 12 months. Insulin secretion, resistance and a disposition index (DI (IV)), a measure of β cell responsiveness in the context of prevailing insulin resistance, were also determined. Results At 12 months, 50% of renal transplant recipients had dysglycemia. Dysglycemia was associated with a dramatic fall in DI (IV) and this loss in β cell function was evident as early as 3 months posttransplantation (23.5 pretransplant; 6.4 at 3 months and 12.2 at 12 months posttransplant). Differences in the β cell response to oral glucose challenge were evident pretransplant in those destined to develop dysglycemia posttransplant (2-hour blood glucose level 5.6 mmol/L versus 6.8 mmol/L; P < 0.01). Conclusions Dysglycemia after renal transplantation is common, and the loss of insulin secretion is a major contributor. Subclinical differences in glucose handling are evident pretransplant in those destined to develop dysglycemia potentially heralding a susceptible β cell which under the stressors associated with transplantation fails.
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Han E, Kim MS, Kim YS, Kang ES. Risk assessment and management of post-transplant diabetes mellitus. Metabolism 2016; 65:1559-69. [PMID: 27621191 DOI: 10.1016/j.metabol.2016.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/13/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023]
Abstract
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.
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Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center; Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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10
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Dabrowska-Zamojcin E, Romanowski M, Dziedziejko V, Maciejewska-Karlowska A, Sawczuk M, Safranow K, Domanski L, Pawlik A. CCL2 gene polymorphism is associated with post-transplant diabetes mellitus. Int Immunopharmacol 2016; 32:62-65. [PMID: 26802601 DOI: 10.1016/j.intimp.2016.01.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 01/01/2016] [Accepted: 01/11/2016] [Indexed: 10/22/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post-transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine.
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Affiliation(s)
| | - Maciej Romanowski
- Department of General and Transplantation Surgery, Pomeranian Medical University in Szczecin, Poland
| | - Violetta Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | | | - Marek Sawczuk
- Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Leszek Domanski
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
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11
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Porrini EL, Díaz JM, Moreso F, Delgado Mallén PI, Silva Torres I, Ibernon M, Bayés-Genís B, Benitez-Ruiz R, Lampreabe I, Lauzurrica R, Osorio JM, Osuna A, Domínguez-Rollán R, Ruiz JC, Jiménez-Sosa A, González-Rinne A, Marrero-Miranda D, Macía M, García J, Torres A. Clinical evolution of post-transplant diabetes mellitus. Nephrol Dial Transplant 2015; 31:495-505. [DOI: 10.1093/ndt/gfv368] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 09/22/2015] [Indexed: 12/11/2022] Open
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12
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Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, Wang T, Liang J, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes 2015; 7:881-90. [PMID: 25676209 DOI: 10.1111/1753-0407.12275] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 01/13/2015] [Accepted: 01/27/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.
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Affiliation(s)
- Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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13
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Langsford D, Dwyer K. Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management. World J Diabetes 2015; 6:1132-51. [PMID: 26322159 PMCID: PMC4549664 DOI: 10.4239/wjd.v6.i10.1132] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 07/06/2015] [Accepted: 08/16/2015] [Indexed: 02/05/2023] Open
Abstract
New-onset diabetes after transplantation (NODAT) is major complication following renal transplantation. It commonly develops within 3-6 mo post-transplantation. The development of NODAT is associated with significant increase in risk of major cardiovascular events and cardiovascular death. Other dysglycemic states, such as impaired glucose tolerance are also associated with increasing risk of cardiovascular events. The pathogenesis of these dysglycemic states is complex. Older recipient age is a consistent major risk factor and the impact of calcineurin inhibitors and glucocorticoids has been well described. Glucocorticoids likely cause insulin resistance and calcineurin inhibitors likely cause β-cell toxicity. The impact of transplantation in incretin hormones remains to be clarified. The oral glucose tolerance test remains the best diagnostic test but other tests may be validated as screening tests. Possibly, NODAT can be prevented by administering insulin early in patients identified as high risk for NODAT. Once NODAT has been diagnosed altering immunosuppression may be acceptable, but creates the difficulty of balancing immunological with metabolic risk. With regard to hypoglycemic use, metformin may be the best option. Further research is needed to better understand the pathogenesis, identify high risk patients and to improve management options given the significant increased risk of major cardiovascular events and death.
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Romanowski M, Dziedziejko V, Maciejewska-Karlowska A, Sawczuk M, Safranow K, Domanski L, Pawlik A. Adiponectin and leptin gene polymorphisms in patients with post-transplant diabetes mellitus. Pharmacogenomics 2015; 16:1243-51. [DOI: 10.2217/pgs.15.71] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Background: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after organ transplantation and may be associated with the use of calcineurin inhibitors (tacrolimus and cyclosporine). Leptin and adiponectin are adipokines and play an important role in the regulation of insulin secretion as well as glucose and lipid metabolism. Aim: The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and development of PTDM. Materials & methods: The study included 323 patients who received kidney transplants and were treated with calcineurin inhibitors (tacrolimus or cyclosporine). Results: The association between adiponectin and leptin gene polymorphisms and PTDM was studied in three models of Cox regression analysis – additive, dominant and recessive. In these three models, the LEP rs2167270 gene polymorphism was statistically significantly associated with increased risk of PTDM. The association between the LEP rs2167270 polymorphism and PTDM was confirmed by multivariate regression analysis. Conclusion: The results of our study suggest an association between the leptin rs2167270 gene A allele and PTDM. Original submitted 27 February 2015; Revision submitted 22 May 2015
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Affiliation(s)
- Maciej Romanowski
- Department of General & Transplantation Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Violetta Dziedziejko
- Department of Biochemistry & Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | | | - Marek Sawczuk
- Faculty of Physical Education & Health Promotion, University of Szczecin, Szczecin, Poland
| | - Krzysztof Safranow
- Department of Biochemistry & Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Leszek Domanski
- Clinical Department of Nephrology, Transplantology & Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, Powstancow Wlkp. 72, 70–111 Szczecin, Poland
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15
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Tokodai K, Amada N, Haga I, Takayama T, Nakamura A. The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation. Diabetes Res Clin Pract 2014; 103:298-303. [PMID: 24468096 DOI: 10.1016/j.diabres.2013.12.049] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 07/10/2013] [Accepted: 12/29/2013] [Indexed: 01/14/2023]
Abstract
AIMS To evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT). METHODS We performed a retrospective study of 145 patients without diabetes who received kidney transplantations at our hospital. The 5-time point OGTT was performed before transplantation. The area under a receiver-operating characteristic curve (aROC) was used for evaluating the predictive power of 5-time point OGTT values. RESULTS Seventeen patients developed NODAT within 1 year after transplantation. All postload plasma glucose (PPG) levels were higher in patients who developed NODAT than in those who did not; fasting plasma glucose levels were not different. The aROC for the area under the glucose concentration-time curve was significantly greater than that for fasting plasma glucose. Univariate and multivariate analyses showed that each PPG level was an independent risk factor for NODAT. Furthermore, patients with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) could be stratified with a 1-h plasma glucose (1h-PG) cut-off point of 8.4 mmol/L. The incidences of NODAT were 23.5%, 16.7%, 9.1%, and 0% for patients with IGT+1h-PG ≥8.4 mmol/L,IGT+1h-PG <8.4 mmol/L, NGT+1h-PG ≥ 8.4 mmol/L, and NGT+1h-PG<8.4 mmol/L, respectively. CONCLUSIONS The area under the glucose concentration-time curve and each PPG concentration during the 5-time point OGTT are strong predictors of NODAT. A 1h-PG cut-off point of 8.4 mmol/L plus NGT/IGT can be used to identify patients at intermediate and high risk of developing NODAT.
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Affiliation(s)
- Kazuaki Tokodai
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai, Japan 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi, 981-8501, Japan.
| | - Noritoshi Amada
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai, Japan 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi, 981-8501, Japan
| | - Izumi Haga
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai, Japan 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi, 981-8501, Japan
| | - Tetsuro Takayama
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai, Japan 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi, 981-8501, Japan
| | - Atsushi Nakamura
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai, Japan 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi, 981-8501, Japan
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16
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Tokodai K, Amada N, Haga I, Nakamura A, Kashiwadate T, Kawagishi N, Ohuchi N. Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin. Int J Endocrinol 2014; 2014:436725. [PMID: 25386190 PMCID: PMC4216713 DOI: 10.1155/2014/436725] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Revised: 09/23/2014] [Accepted: 10/01/2014] [Indexed: 12/27/2022] Open
Abstract
Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset diabetes after transplantation (NODAT) in kidney transplant candidates, who had several predispositions for fluctuated HbA1c levels. Methods. We performed a retrospective study of 119 patients without diabetes who received kidney transplantation between March 2000 and January 2012. Univariate and multivariate logistic regression analyses were used to investigate the association of several parameters with NODAT. Predictive discrimination of HbA1c was assessed using a receiver-operating characteristic curve. Results. Seventeen patients (14.3%) developed NODAT within 1 year of transplantation. Univariate logistic regression analysis revealed that recipient age, gender, and HbA1c were predictors of NODAT. In the multivariate analysis, the association between pretransplant HbA1c and NODAT development did not reach statistical significance (P = 0.07). To avoid the strong influence of high-dose erythropoietin on HbA1c levels, we performed subgroup analyses on 85 patients receiving no or low-dose (≤6000 IU/week) erythropoietin. HbA1c was again an independent predictor for NODAT. Receiver-operating characteristic analysis revealed a cut-off value of 5.2% with an optimal sensitivity of 64% and specificity of 78% for predicting NODAT. Conclusions. Our results reveal that the pretransplant HbA1c level is a useful predictor for NODAT in patients receiving no or low-dose erythropoietin.
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Affiliation(s)
- Kazuaki Tokodai
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai 980-8574, Japan
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
- *Kazuaki Tokodai:
| | - Noritoshi Amada
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai 980-8574, Japan
| | - Izumi Haga
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai 980-8574, Japan
| | - Atsushi Nakamura
- Department of Surgery, Sendai Shakaihoken Hospital, Sendai 980-8574, Japan
| | | | - Naoki Kawagishi
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
| | - Noriaki Ohuchi
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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17
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Georgakopoulou EA, Scully C. Systemic use of non-biologic agents in orofacial diseases: other immunomodulatory agents. Oral Dis 2013; 21:273-82. [PMID: 24028818 DOI: 10.1111/odi.12172] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 07/31/2013] [Accepted: 08/01/2013] [Indexed: 11/29/2022]
Abstract
Systemic non-biologic agents have long been in clinical use in medicine--often with considerable efficacy, albeit with some adverse effects--as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non-biologic agents (NBAs) include a range of agents, most importantly the corticosteroids (steroids). Previous articles by us in this series have discussed systemic use of corticosteroids and purine synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors, thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final article.
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Affiliation(s)
- E A Georgakopoulou
- Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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18
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New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation 2013; 93:1189-95. [PMID: 22475764 DOI: 10.1097/tp.0b013e31824db97d] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
New-Onset Diabetes After Transplantation (NODAT) is an increasingly recognized severe metabolic complication of kidney transplantation causing lower graft function and survival and reduced long-term patient survival mainly due to cardiovascular events. The real incidence of NODAT after kidney transplantation is difficult to establish, because different classification systems and definitions have been employed over the years. Several risk factors, already present before or arising after transplantation, in particular the employed immunosuppressive regimens, have been related to the development of NODAT. However the responsible pathogenic mechanisms are still far to be perfectly known. Awareness of NODAT and of the NODAT-related factors is of paramount importance for the clinicians in order to individuate higher risk patients and arrange screening strategies. The risk of NODAT can be reduced by planning preventive measures and by tailoring immunosuppressive regimens according to the patient characteristics. Once NODAT has been diagnosed, the administration of specific anti-hyperglycemic therapy is mandatory to reach a tight glycemic control, which contributes to significantly reduce posttransplant mortality and morbidity.
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19
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Hackman KL, Snell GI, Bach LA. An unexpectedly high prevalence of undiagnosed diabetes in patients awaiting lung transplantation. J Heart Lung Transplant 2013; 32:86-91. [DOI: 10.1016/j.healun.2012.10.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Revised: 10/08/2012] [Accepted: 10/17/2012] [Indexed: 11/29/2022] Open
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20
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Cañas L, Bayés B, Granada ML, Ibernon M, Porrini E, Benítez R, Díaz JM, Lauzurica R, Moreso F, Torres A, Lampreabe I, Serra A, Romero R. Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation? Clin Transplant 2011; 26:259-66. [PMID: 22150949 DOI: 10.1111/j.1399-0012.2011.01490.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
UNLABELLED The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). METHODS We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. RESULTS Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. CONCLUSIONS Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.
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Affiliation(s)
- Laura Cañas
- Nephrology Department, Hospital Germans Trias i Pujol, UAB, Badalona, Spain.
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21
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Cha BS, Moon JH. Management of Posttransplantation Diabetes Mellitus (PTDM). KOREAN JOURNAL OF TRANSPLANTATION 2011. [DOI: 10.4285/jkstn.2011.25.1.8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Bong Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hoon Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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22
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McFarlane SI, McCullough PA, Sowers JR, Soe K, Chen SC, Li S, Vassalotti JA, Stevens LA, Salifu MO, Kurella Tamura M, Bomback AS, Norris KC, Collins AJ, Bakris GL, Whaley-Connell AT, KEEP Steering Committee. Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations: prevalence of and risk factors for diabetes mellitus in CKD in the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 2011; 57:S24-31. [PMID: 21338847 PMCID: PMC3237700 DOI: 10.1053/j.ajkd.2010.11.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Collaborators] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Accepted: 11/08/2010] [Indexed: 11/11/2022]
Abstract
BACKGROUND Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown. METHODS This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. RESULTS CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14). CONCLUSIONS Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.
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Affiliation(s)
- Samy I McFarlane
- Division of Endocrinology, SUNY-Downstate and Kings County Hospital Centers, Brooklyn, NY 11203, USA.
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Collaborators
George Bakris, Peter McCullough, Andrew Bomback, Claudine Jurkovitz, Bryan Kestenbaum, Louis Kuritzky, Samy McFarlane, Rajendra H Mehta, Keith Norris, Michael Shlipak, James Sowers, Manjula Kurella Tamura, Lesley Stevens, Adam Whaley-Connell, Bryan Becker, Allan Collins, Andrew Narva, Nilka Rios Burrows, Joseph Vassalotti, Wendy Brown, Michael Klag, Shu-Cheng Chen, Dennis L Andress, Reshma Kewalramani, Jose A Menoyo,
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23
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Räkel A, Karelis AD. New-onset diabetes after transplantation: risk factors and clinical impact. DIABETES & METABOLISM 2011; 37:1-14. [PMID: 21295510 DOI: 10.1016/j.diabet.2010.09.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 09/17/2010] [Accepted: 09/21/2010] [Indexed: 02/06/2023]
Abstract
With improvements in patient and graft survival, increasing attention has been placed on complications that contribute to long-term patient morbidity and mortality. New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation, and is a strong predictor of graft failure and cardiovascular mortality in the transplant population. Risk factors for NODAT in transplant recipients are similar to those in non-transplant patients, but transplant-specific risk factors such as hepatitis C (HCV) infection, corticosteroids and calcineurin inhibitors play a dominant role in NODAT pathogenesis. Management of NODAT is similar to type 2 diabetes management in the general population. However, adjusting the immunosuppressant regimen to improve glucose tolerance must be weighed against the risk of allograft rejection. Lifestyle modification is currently the strategy with the least risk and the most benefit.
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Affiliation(s)
- A Räkel
- Department of Medicine, hôpital Saint-Luc, centre de recherche, centre hospitalier, University of Montreal, René-Lévesque-Est, Québec, Canada.
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