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1
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Chen S, Bowen DG, Liu K, Vidot H. Hypomagnesaemia, an independent risk factor for the development of post-transplant diabetes mellitus in liver and renal transplant recipients? A systematic review. J Hum Nutr Diet 2024; 37:1407-1419. [PMID: 39073157 DOI: 10.1111/jhn.13354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/21/2024] [Accepted: 07/09/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Post-transplantation diabetes mellitus (PTDM) is common after solid organ transplantation. In the past decade, there has been increasing interest in the association between hypomagnesaemia and the development of PTDM. This systematic review aimed to investigate the current knowledge regarding the association between hypomagnesaemia and PTDM in adult liver and renal transplant recipients. METHODS A literature search of five databases, Medline, Embase, ProQuest, Scopus and Google Scholar, as well as article reference lists, was performed. Eligible studies that focused on adult liver and renal transplant recipients without pretransplantation hyperglycaemia or diabetes were included. Other eligibility criteria included quantitative studies which reported magnesium concentrations, studies with at least 6 months of follow-up, and studies published in English. The Newcastle-Ottawa Assessment Tool was used for the quality assessment. RESULTS In total, 12 studies were included in the final analysis. Eleven focused on renal transplantation and one on liver transplantation. All studies were medium to high quality with eight out of 12 achieving the highest rating of nine. Eight studies found a negative association between either pretransplant or early post-transplant serum magnesium concentration and the risk of PTDM, three studies found no association between these two variables, and one study found a positive association between the magnesium concentration at 8 weeks after transplantation and glycosylated haemoglobin A1C. CONCLUSIONS Further large-scale prospective studies with at least 6 months of follow-up are needed to confirm these findings, particularly in liver transplantation, to further clarify and explore the relationship between hypomagnesaemia and PTDM.
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Affiliation(s)
- Shujie Chen
- Sydney Nursing School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia
| | - David Geoffrey Bowen
- Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Helen Vidot
- Department of Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
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2
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Macías Ruiz MDC, Cuenca Bermejo L, Veronese N, Fernández Villalba E, González Cuello AM, Kublickiene K, Raparelli V, Norris CM, Kautzky-Willer A, Pilote L, Barbagallo M, Dominguez L, Herrero MT. Magnesium in Kidney Function and Disease-Implications for Aging and Sex-A Narrative Review. Nutrients 2023; 15:1710. [PMID: 37049550 PMCID: PMC10097335 DOI: 10.3390/nu15071710] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/22/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012-2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there's a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.
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Affiliation(s)
- María del Carmen Macías Ruiz
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Lorena Cuenca Bermejo
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Nicola Veronese
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
| | - Emiliano Fernández Villalba
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Ana María González Cuello
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
| | - Karolina Kublickiene
- Department of Renal Medicine, Institution for Clinical Science, Intervention and Technology, Karolinska Institute, 17177 Stockholm, Sweden
| | - Valeria Raparelli
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Colleen M. Norris
- Faculty of Nursing, University of Alberta, Edmonton, AB T6G 2R3, Canada
- Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, AB T5J 3E4, Canada
| | - Alexandra Kautzky-Willer
- Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria
| | - Louise Pilote
- Research Institute of McGill University Health Centre, Divisions of General Internal Medicine and Clinical Epidemiology, McGill University, Montreal, QC H4A 3J1, Canada
| | - Mario Barbagallo
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
| | - Ligia Dominguez
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy
- Faculty of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
| | - María Trinidad Herrero
- Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, Biomedical Institute of Murcia (IMIB-Pascual Parrilla), School of Medicine, Campus Mare Nostrum, UniWell, University of Murcia, 30100 Murcia, Spain
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3
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Duni A, Koutlas V, Tsitouridis A, Tzalavra E, Oikonomaki T, Kitsos A, Rapsomanikis KP, Alekos J, Tatsis V, Pappas C, Mitsis M, Dounousi E. Longitudinal Assessment of Electrolyte Disorders in a Cohort of Chronic Stable Kidney Transplant Recipients. Transplant Proc 2021; 53:2786-2792. [PMID: 34690001 DOI: 10.1016/j.transproceed.2021.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND Kidney transplantation is complicated by various electrolyte disturbances with variable reported prevalence and incidence and of multifactorial pathogenesis. The aim of our study was the retrospective longitudinal assessment of the serum electrolytes in a cohort of stable kidney transplant recipients (KTRs) and the possible associated parameters, including graft function and medications. METHODS We included 93 stable KTRs under follow-up in our hospital's kidney transplant unit. Serum magnesium, calcium, phosphorus, potassium, sodium, and urine sodium levels were recorded retrospectively during 3 consecutive years. In addition, comorbidities, biochemical parameters, medications, and graft function (estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation and 24-hour urinary protein [uTpr]) were recorded. RESULTS Mean age at baseline was 51 ± 11 years; 64 KTRs were men (68.8%), 17 (18.3%) had diabetes, 79 (85%) had hypertension, and 11 (11.8%) had cardiovascular disease. Mean eGFR and uTpr (mg/24 h) at study initiation were 47.1 ± 13.5 mL/min/1.73 m2 and 369.4 ± 404.2 mg/24 h, respectively. Hypomagnesemia was the most common disturbance observed in 21.7% of KTRs. Patients with hypomagnesemia displayed higher parathyroid hormone levels and more frequently had diabetes. Hypophosphatemia was recorded in 9.7% of KTRs during the first year. Hyperkalemia, hypokalemia, and hypercalcemia were rare (<5%). Mean serum and urine sodium concentration remained stable during the study, whereas urinary sodium levels showed a positive correlation with uTpr (P < .05). CONCLUSIONS In our cohort of KTRs, there were no significant electrolyte disorders, either in terms of frequency or severity, with hypomagnesemia being the most prevalent disturbance. The identification of potential associated risk factors and clinical data correlations are pivotal for the development of individualized and evidence-based therapeutic approach and decisions.
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Affiliation(s)
- Anila Duni
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece
| | - Vasileios Koutlas
- Department of Surgery and Kidney Transplant Unit, University Hospital of Ioannina, Ioannina, Greece
| | | | - Eirini Tzalavra
- Department of Surgery and Kidney Transplant Unit, University Hospital of Ioannina, Ioannina, Greece
| | - Theodora Oikonomaki
- Department of Nephrology, Evaggelismos General Hospital of Athens, Athens, Greece
| | - Athanasios Kitsos
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece
| | | | - John Alekos
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece
| | - Vasileios Tatsis
- Department of Surgery and Kidney Transplant Unit, University Hospital of Ioannina, Ioannina, Greece
| | - Charalampos Pappas
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece
| | - Mixalis Mitsis
- Department of Surgery and Kidney Transplant Unit, University Hospital of Ioannina, Ioannina, Greece
| | - Evangelia Dounousi
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece.
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4
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Panthofer AM, Lyu B, Astor BC, Singh T, Aziz F, Mandelbrot D, Parajuli S, Mohamed M, Djamali A, Garg N. Post-kidney transplant serum magnesium exhibits a U-shaped association with subsequent mortality: an observational cohort study. Transpl Int 2021; 34:1853-1861. [PMID: 34081803 DOI: 10.1111/tri.13932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/10/2021] [Accepted: 05/27/2021] [Indexed: 11/30/2022]
Abstract
Hypomagnesemia is common in kidney transplant recipients (KTRs). We sought to explore the relationship between Mg and outcomes in KTRs, which may be associated with mortality and thus may be a potential intervention target to improve outcomes. We followed KTRs performed between 01/2000 and 6/2016 at a large US transplant center from 6 months post-transplant to graft failure, death, or loss to follow-up. Using Mg as a time-dependent variable, associations between Mg and outcomes any time after 6 months post-transplant were evaluated. 3680 KTRs with 50 413 Mg measurements met inclusion criteria. 657 deaths occurred over a median follow-up of 5.1 years. Compared to Mg of 1.5-1.8 mg/dl, both lower (HR 1.17, 95% confidence interval (CI): 1.07-1.28) and higher (HR 1.16, 95% CI: 1.09-1.23) Mg levels were associated with greater risk of mortality. Similar U-shaped associations were observed for Mg and cardiovascular disease-related mortality (HR for Mg ≤1.5 mg/dl: 1.31; CI: 1.03-1.68) and infection-related mortality (HR for Mg ≤1.5 mg/dl: 1.28; CI: 1.09-1.51), although relationships for Mg >1.8 mg/dl were not statistically significant. Mg exhibits a U-shaped association with mortality in KTRs, with levels between 1.5 and 1.8 mg/dl associated with the lowest risk.
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Affiliation(s)
- Annalise M Panthofer
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Beini Lyu
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brad C Astor
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Tripti Singh
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Maha Mohamed
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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5
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Lahav I, Steinmetz T, Molcho M, Lev N, Agur T, Nesher E, Rozen-Zvi B, Rahamimov R. The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality. Front Med (Lausanne) 2021; 8:690273. [PMID: 34322504 PMCID: PMC8310919 DOI: 10.3389/fmed.2021.690273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/10/2021] [Indexed: 11/24/2022] Open
Abstract
Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality. Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model. Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18–3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17–3.86, p = 0.013) in multivariate analysis. Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.
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Affiliation(s)
- Itay Lahav
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tali Steinmetz
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Maya Molcho
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Neta Lev
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Timna Agur
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Eviatar Nesher
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Organ Transplantation, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Benaya Rozen-Zvi
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
| | - Ruth Rahamimov
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel.,Department of Organ Transplantation, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
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6
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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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7
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Sidhaye A, Goldswieg B, Kaminski B, Blackman SM, Kelly A. Endocrine complications after solid-organ transplant in cystic fibrosis. J Cyst Fibros 2019; 18 Suppl 2:S111-S119. [DOI: 10.1016/j.jcf.2019.08.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/18/2019] [Accepted: 08/19/2019] [Indexed: 01/07/2023]
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8
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Pathogenesis and treatment of electrolyte problems post transplant. Curr Opin Pediatr 2019; 31:213-218. [PMID: 30585865 DOI: 10.1097/mop.0000000000000715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Electrolyte abnormalities posttransplant are common occurrences that can have significant short-term and long-term effects on graft outcome and patient quality of life. Understanding the pathophysiology of these electrolyte derangements can help guide management to optimize bone health and minimize cardiovascular disease. This review explores the pathogenesis of the most common postrenal transplant electrolytes abnormalities as well as current treatment options. RECENT FINDINGS Clarifications of the role of FGF-23 has improved our understanding of posttransplant bone disease in addition to the known roles of hyperparathyroidism and vitamin D. The mechanisms of renal electrolyte wasting by immunosuppressive agents give insight into potential treatment options for hyperkalemia and hypomagnesemia. SUMMARY Understanding the pathogenesis of the common electrolyte abnormalities found post renal transplant may lead to targeted treatment options that in turn may improve transplant complications. Further studies are required to evaluate the effects on long-term outcomes of renal allografts.
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9
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Abstract
Solid organ transplantation (SOT) is a life-saving procedure and an established treatment for patients with end-stage organ failure. However, transplantation is also accompanied by associated cardiovascular risk factors, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM develops in 10-20% of patients with kidney transplants and in 20-40% of patients who have undergone other SOT. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from predisposing factors (similar to type 2 diabetes mellitus) but also as a result of specific post-transplant risk factors. Although PTDM has many characteristics in common with type 2 diabetes mellitus, the prevention and treatment of the two disorders are often different. Over the past 20 years, the lifespan of patients who have undergone SOT has increased, and PTDM becomes more common over the lifespan of these patients. Accordingly, PTDM becomes an important condition not only to be aware of but also to treat. This Review presents the current knowledge on PTDM in patients receiving kidney, heart, liver and lung transplants. This information is not only for transplant health providers but also for endocrinologists and others who will meet these patients in their clinics.
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Affiliation(s)
- Trond Jenssen
- Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Anders Hartmann
- Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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10
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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11
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González-Villalva A, Colín-Barenque L, Bizarro-Nevares P, Rojas-Lemus M, Rodríguez-Lara V, García-Pelaez I, Ustarroz-Cano M, López-Valdez N, Albarrán-Alonso JC, Fortoul TI. Pollution by metals: Is there a relationship in glycemic control? ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2016; 46:337-343. [PMID: 27552445 DOI: 10.1016/j.etap.2016.06.023] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 06/20/2016] [Accepted: 06/21/2016] [Indexed: 06/06/2023]
Abstract
There are evidences of environmental pollution and health effects. Metals are pollutants implicated in systemic toxicity. One of the least studied effects, but which is currently becoming more important, is the effect of metals on glycemic control. Metals have been implicated as causes of chronic inflammation and oxidative stress and are associated to obesity, hyperglycemia and even diabetes. Arsenic, iron, mercury, lead, cadmium and nickel have been studied as a risk factor for hyperglycemia and diabetes. There is another group of metals that causes hypoglycemia such as vanadium, chromium, zinc and magnesium by different mechanisms. Zinc, magnesium and chromium deficiency is associated with increased risk of diabetes. This review summarizes some metals involved in glycemic control and pretends to alert health professionals about considering environmental metals as an important factor that could explain the poor glycemic control in patients. Further studies are needed to understand this poorly assessed problem.
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Affiliation(s)
- Adriana González-Villalva
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Laura Colín-Barenque
- Laboratorio de Neuromorfología, FES Iztacala, UNAM CP 54090 Edo. de México, Mexico.
| | - Patricia Bizarro-Nevares
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Marcela Rojas-Lemus
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Vianey Rodríguez-Lara
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Isabel García-Pelaez
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Martha Ustarroz-Cano
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Nelly López-Valdez
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Juan Carlos Albarrán-Alonso
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
| | - Teresa I Fortoul
- Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico.
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Sinangil A, Celik V, Barlas S, Sakaci T, Koc Y, Basturk T, Akin EB, Ecder T. New-Onset Diabetes After Kidney Transplantation and Pretransplant Hypomagnesemia. Prog Transplant 2016; 26:55-61. [PMID: 27136250 DOI: 10.1177/1526924816633949] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
AIM Hypomagnesemia is a frequent finding in kidney transplant patients and plays a causal role in insulin resistance and diabetes. The aim of this study was to investigate whether the pretransplant magnesium (Mg) level is a risk factor for the development of new-onset diabetes after kidney transplantation (NODAT) and the presence of relationship between pretransplant hypomagnesemia and the development period of NODAT. METHODS Four hundred and nineteen nondiabetic renal transplant recipients were evaluated retrospectively. The patients were divided into NODAT and non-NODAT groups. The time of diagnosis of patients with NODAT was divided into 0 to 3, 3 to 6, 6 to 12 months, and after 12 months. Patients' characteristics and pretransplant Mg levels in NODAT were compared with non-NODAT, and it was investigated whether pretransplant hypomagnesemia was a risk factor for the development of NODAT. RESULTS Totally 70 (16.6%) patients (36 female [F], mean age 51.7 ± 8.2 years) were diagnosed with NODAT. Three hundred and forty-nine patients (115 F, mean age 43.2 ± 12.5 years) did not have NODAT. Pretransplant mean Mg level was 1.97 ± 0.40 mg/dL in patients with NODAT, while it was 2.5 ± 0.45 mg/dL in non-NODAT patients (P < .001). Serum Mg level was found to be similar in subgroups according to the development period of NODAT (P = .07). When patients were stratified according to quartiles of Mg level, the frequency of NODAT was significantly higher in patients in the lower quartile (Mg < 2.1 mg/dL; P < .001). Older age, high body mass index, and low pretransplant serum Mg levels were established as risk factors for developing NODAT. According to the quartile of Mg level, the risk of developing NODAT was highest in the lowest quartile. CONCLUSION Pretransplant hypomagnesemia is an independent risk factor of NODAT. Therefore, it is necessary to closely monitor the Mg levels in the posttransplant period.
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Affiliation(s)
- Ayse Sinangil
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
| | - Vedat Celik
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
| | - Soykan Barlas
- Renal Transplantation Unit, Istanbul Bilim University, Istanbul, Turkey
| | - Tamer Sakaci
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Yener Koc
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Taner Basturk
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Emin Baris Akin
- Renal Transplantation Unit, Istanbul Bilim University, Istanbul, Turkey
| | - Tevfik Ecder
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
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Yu H, Kim H, Baek CH, Baek SD, Jeung S, Han DJ, Park SK. Risk factors for new-onset diabetes mellitus after living donor kidney transplantation in Korea - a retrospective single center study. BMC Nephrol 2016; 17:106. [PMID: 27473469 PMCID: PMC4966790 DOI: 10.1186/s12882-016-0321-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 07/21/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND New-onset diabetes mellitus after transplantation (NODAT) is a serious complication following renal transplantation. The aim of this study was to identify the risk factors for the development of NODAT in Korean transplant patients. METHODS Recipients who underwent living donor kidney transplantation between January 2009 and April 2012 at Asan Medical Center were reviewed. Diagnosis of NODAT was defined according to the American Diabetes Association criteria. RESULTS A total of 418 patients were enrolled. NODAT was diagnosed in 85 (20.4 %) patients within 1 year. By multivariate analysis, old age (odds ratio [OR], 1.05; 95 % Confidence interval [CI]: 1.01-1.08), family history of diabetes mellitus (OR, 2.48; 95 % CI: 1.04-5.94), pre-transplant high serum glucose level (OR, 1.04; 95 % CI: 1.01-1.08), and obesity (OR, 3.46; 95 % CI: 1.55-7.73) were independent risk factors for NODAT. CONCLUSION Old age, family history of diabetes, pre-transplant high plasma glucose level, and obesity are independent factors associated with the development of diabetes after renal transplantation. In contrast, serum magnesium levels and the use of tacrolimus are not associated with the development of NODAT.
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Affiliation(s)
- Hoon Yu
- Division of a Nephrology, Gangneung Asan hospital, University of Ulsan College of Medicine, Gangneung, South Korea
| | - Hyosang Kim
- Division of a Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chung Hee Baek
- Division of a Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seung Don Baek
- Division of a Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Soomin Jeung
- Division of a Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Su-Kil Park
- Division of a Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
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Cheungpasitporn W, Thongprayoon C, Harindhanavudhi T, Edmonds PJ, Erickson SB. Hypomagnesemia linked to new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis. Endocr Res 2016; 41:142-7. [PMID: 26934195 DOI: 10.3109/07435800.2015.1094088] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased mortality. The objective of this meta-analysis was to evaluate the risk of NODAT in patients with hypomagnesemia. METHODS A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through May, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of NODAT in patients with hypomagnesemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS Five cohort studies with 1699 patients were included in the analysis to assess the risk of NODAT in patients with hypomagnesemia. The pooled RR of NODAT in patients with hypomagnesemia was 1.25 (95% CI, 1.08-1.45). When meta-analysis was limited only to studies with the post-transplant hypomagnesemia, the pooled RR of NODAT was 1.22 (95% CI, 1.09-1.38). CONCLUSION Our meta-analysis demonstrates a significant association between hypomagnesemia and NODAT in kidney transplant recipients. This finding suggests the need for a large randomized controlled trial-with very careful attention to assess the effects of normalizing Mg levels and the risk of NODAT.
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Affiliation(s)
| | - Charat Thongprayoon
- a Division of Nephrology and Hypertension , Mayo Clinic , Rochester , MN , USA
| | - Tasma Harindhanavudhi
- b Division of Diabetes, Endocrinology and Metabolism , University of Minnesota , Minneapolis , MN , USA
| | | | - Stephen B Erickson
- a Division of Nephrology and Hypertension , Mayo Clinic , Rochester , MN , USA
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15
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Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 2016; 37:37-61. [PMID: 26650437 PMCID: PMC4740345 DOI: 10.1210/er.2015-1084] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
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Affiliation(s)
- Vijay Shivaswamy
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Brian Boerner
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Jennifer Larsen
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
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16
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Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant 2015; 5:183-95. [PMID: 26722646 PMCID: PMC4689929 DOI: 10.5500/wjt.v5.i4.183] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 08/19/2015] [Accepted: 09/25/2015] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.
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Zelt JGE, McCabe KM, Svajger B, Barron H, Laverty K, Holden RM, Adams MA. Magnesium Modifies the Impact of Calcitriol Treatment on Vascular Calcification in Experimental Chronic Kidney Disease. J Pharmacol Exp Ther 2015; 355:451-62. [PMID: 26487689 DOI: 10.1124/jpet.115.228106] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 10/06/2015] [Indexed: 03/08/2025] Open
Abstract
Chronic kidney disease (CKD) patients are commonly treated with vitamin D analogs, such as calcitriol. Recent epidemiologic evidence revealed a significant interaction between vitamin D and magnesium, since an inverse relationship between vitamin D levels and mortality mainly occurs in patients with a high magnesium intake. The aim of the study was to assess the mechanisms involved by determining whether magnesium alone or combined with calcitriol treatments differentially impacts vascular calcification (VC) in male Sprague-Dawley rats with adenine-induced CKD. Treatment with moderate doses of calcitriol (80 μg/kg) suppressed parathyroid hormone to near or slightly below control levels. Given alone, this dose of calcitriol increased the prevalence of VC; however, when magnesium was given in combination, the severity of calcification was attenuated in the abdominal aorta (51% reduction), iliac (44%), and carotid arteries (46%) compared with CKD controls. The decreases in vascular calcium content were associated with a 20-50% increase in vascular magnesium. Calcitriol treatment alone significantly decreased TRPM7 protein (↓ to ∼11%), whereas the combination treatment increased both mRNA (1.7×) and protein (6.8×) expression compared with calcitriol alone. In summary, calcitriol increased VC in certain conditions, but magnesium prevented the reduction in TRPM7 and reduced the severity of VC, thereby increasing the bioavailable magnesium in the vascular microenvironment. These findings suggest that modifying the adverse effect profile of calcitriol with magnesium may be a plausible approach to benefiting the increasing number of CKD patients being prescribed calcitriol.
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Affiliation(s)
- Jason G E Zelt
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Kristin M McCabe
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Bruno Svajger
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Henry Barron
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Kim Laverty
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Rachel M Holden
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
| | - Michael A Adams
- Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen's University, Kingston, Ontario, Canada
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18
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Le Fur A, Fournier MC, Gillaizeau F, Masson D, Giral M, Cariou B, Cantarovich D, Dantal J. Vitamin D deficiency is an independent risk factor for PTDM after kidney transplantation. Transpl Int 2015; 29:207-15. [DOI: 10.1111/tri.12697] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 04/14/2015] [Accepted: 09/25/2015] [Indexed: 01/05/2023]
Affiliation(s)
- Awena Le Fur
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
| | - Marie-Cécile Fournier
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | - Florence Gillaizeau
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | | | - Magali Giral
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
- EA 4275 - SPHERE Biostatistics, Pharmacoepidemiology, and Human Sciences Research; Nantes University Hospital; Nantes France
| | - Bertrand Cariou
- Endocrinology Clinic; Nantes University Hospital; Nantes France
- INSERM UMR 1087; CNRS UMR 6291; Thorax Institute; Nantes University Hospital; Nantes France
| | - Diego Cantarovich
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
| | - Jacques Dantal
- Institute of Transplantation, Urology and Nephrology (ITUN); Nantes University Hospital; Nantes France
- INSERM UMR 1064; Nantes University Hospital; Nantes France
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Huang JW, Famure O, Li Y, Kim SJ. Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation. J Am Soc Nephrol 2015; 27:1793-800. [PMID: 26449610 DOI: 10.1681/asn.2015040391] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Accepted: 08/13/2015] [Indexed: 12/13/2022] Open
Abstract
Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.
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Affiliation(s)
- Johnny W Huang
- Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Olusegun Famure
- Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Yanhong Li
- Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - S Joseph Kim
- Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology and the Renal Transplant Program, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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20
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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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21
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Van Laecke S, Van Biesen W. Hypomagnesaemia in kidney transplantation. Transplant Rev (Orlando) 2015; 29:154-60. [PMID: 26001746 DOI: 10.1016/j.trre.2015.05.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2015] [Accepted: 05/03/2015] [Indexed: 01/14/2023]
Abstract
In the era of calcineurin inhibitors, hypomagnesaemia is a very common finding in kidney transplant recipients. Especially the first weeks after transplantation it is the rule rather than the exception. Hypomagnesaemia or low magnesium intake have been associated with a higher mortality or more cardiovascular events in the general population, but this association has never been explored in kidney transplant recipients, despite their increased cardiovascular risk. Kidney transplant recipients with pre- or post-transplant hypomagnesaemia seem to have an aberrant glucose metabolism and develop diabetes mellitus more frequently. Moreover, observations from alternate study populations, animal experiments or in vitro studies suggest a possible role of magnesium deficiency in graft dysfunction, bone metabolism and transplant immunology. Future observational and especially interventional studies should further define whether and to what extent we should make effort to correct this electrolyte disturbance in transplant recipients. Considering the mechanism of renal magnesium wasting, normalizing the serum magnesium concentration by oral supplementation alone might turn out to be cumbersome in kidney transplant recipients.
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Affiliation(s)
| | - Wim Van Biesen
- Renal Division, Ghent University Hospital, Ghent, Belgium.
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