New-onset Diabetes After Kidney Transplantation Research Articles

New-onset diabetes after kidney transplantation revealing HNF1B-associated disease.

SummaryMolecular alterations of the transcription factor hepatocyte nuclear factor 1B (HNF1B) are associated with systemic disease, with kidney disease and maturity-onset diabetes of the young (MODY) as the most characteristic manifestations. Other features comprise pancreatic exocrine insufficiency, liver and biliary anomalies, and genital tract malformations. HNF1B-associated disease is clinically heterogeneous, and therefore the diagnosis is challenging. The authors describe the case of a 19-year-old man with new-onset diabetes after kidney transplantation (NODAT). The kidney disease presented during fetal life as bilateral hyperechogenic kidneys. Renal function progressively deteriorated during childhood, and at the age of 19, the patient was submitted to a living-kidney transplant. Two weeks after transplant, NODAT developed. Given the young age and normal body weight, NODAT was unexpected, and the possibility of HNF1B-associated disease was considered. Screening for mutations in HNF1B was undertaken, and a known mutation was found. As this case highlights, HNF1B-associated disease should be considered when NODAT unexpectedly develops in young kidney transplant recipients with a suggestive renal disease.Learning pointsHNF1B anomalies are associated with systemic disease, including kidney disease, diabetes mellitus, pancreatic exocrine insufficiency, liver test abnormalities and genital tract malformations.Phenotype is variable and there are no pathognomonic manifestations, but kidney disease appears to be the most common feature and diabetes the most frequent extra-renal phenotype.Spontaneous gene alterations are common, and the lack of family history should not exclude the diagnosis.HNF1B defects should be considered when NODAT develops in a young adult kidney transplant recipient with a suggestive kidney disease and without extensive risk factors for diabetes.The most appropriate treatment for HNF1B-associated diabetes is not established, but immunosuppressive therapy superimposed on a beta-cell dysfunction seems to determine the need for insulin therapy after a variable period.Immunosupressive regimens free of calcineurin inhibitors should be considered in patients with HNF1B-associated disease to minimize the risk of developing NODAT.

Serum uric acid is an independent predictor of new-onset diabetes after living-donor kidney transplantation

BackgroundWe investigated whether serum uric acid (SUA) levels before kidney transplantation predict new-onset diabetes after kidney transplantation (NODAT) and compared SUA levels with known risk factors for NODAT by prospective cohort study.MethodsA total of 151 adult kidney recipients without diabetes (84 men, 67 women) who underwent living-donor kidney transplantation between 2001 and 2011 were followed in this study. The Cox proportional hazards model was used to analyse the risk of NODAT.ResultsDuring the follow-up period (median 3.3 years, range 0–10 years), 32 (21.2%) adult kidney recipients without diabetes developed NODAT, and an incidence rate was 5.6 per 100 person-years and a 10-year cumulative incidence of 26.9%. When subjects were stratified by SUA levels into tertiles, the patients in the highest tertile (> 8.6 mg/dl for men, > 7.7 mg/dl for women) had a significantly higher risk of NODAT than the patients in the lower 2 tertiles (log-rank test, P = 0.03). In the univariate analysis, increased level of SUA was associated with NODAT (hazard ratio 1.27 [95% CI 1.04–1.55], P = 0.01). In the multivariate analysis, increased level of SUA was significantly associated with NODAT after correction by any factors, e.g. (age, sex, family history of diabetes, BMI, HbA1c, serum creatinine, tacrolimus, HCV) factors directly affecting the SUA value (1.26 [1.02–1.56], P = 0.03), risk factors for T2DM onset (1.34 [1.10–1.64], P = 0.03), and factors previously reported risk factors for NODAT (1.36 [1.11–1.66], P = 0.003).ConclusionSUA independently predicts NODAT in living-donor kidney transplantation patients.

Association of Body Mass Index and the Risk of New-Onset Diabetes After Kidney Transplantation: A Meta-analysis

ObjectiveTo comprehensively examine the correlation between body mass index (BMI) and the risk of new-onset diabetes after kidney transplantation (NODAT). MethodsThe electronic databases Pubmed, Embase, and Cochrane Library, updated in December 2016, were searched, and a literature review was conducted as well to identify relevant research studies. With the use of R 3.12 software, the association between BMI and NODAT risk was analyzed by means of a meta-analysis, with the mean differences (MDs) and their 95% confidence intervals (CIs) as effect indexes. Publication bias was assessed with the use of the Egger test. A sensitivity analysis was performed by excluding 1 study at a time. And the overall morbidity of NODAT was calculated. ResultsIn the meta-analysis, 55 eligible studies involving 15,458 kidney transplantation cases were included. After the heterogeneity test, the random-effects model was used to calculate the pooled results of the effect indexes. The results of the meta-analysis showed that BMI was an independent risk factor of NODAT (MD, 1.88; 95% CI, 1.48–2.27). No publication bias was found among the included studies (t = 0.3417; P = 0.7339). The sensitivity analysis revealed that the pooled MD did not reverse after ignoring 1 study at a time. In addition, the overall morbidity of NODAT was 21% (95% CI, 21%–23%). ConclusionsOur results suggest that BMI is an independent risk factor for NODAT.

The Risk for New-Onset Diabetes Mellitus after Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis.

New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased rates of mortality. The objective of this meta-analysis was to evaluate the risk for NODAT in patients with autosomal dominant polycystic kidney disease (ADPKD). A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through July 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk for NODAT in patients with ADPKD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Included in the analysis were 12 cohort studies, which comprised 1379 patients with ADPKD of a total of 9849 patients who had undergone kidney transplants. The pooled RRs of NODAT in patients with ADPKD were 1.92 (95% CI, 1.36 to 2.70). When meta-analysis was limited only to studies with confounder-adjusted analysis, the pooled RRs for NODAT were 1.98 (95% CI, 1.33 to 2.94). However, the association between NODAT requiring insulin treatment was insignificant, with pooled RRs of 1.57 (95% CI, 0.75 to 3.27). Our meta-analysis demonstrates a significant association between ADPKD and NODAT in recipients of kidney transplants. The findings of this study may impact clinical management and follow up for patients with ADPKD after kidney transplantation.

Hypomagnesemia linked to new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis

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.

New-Onset Diabetes After Kidney Transplantation and Pretransplant Hypomagnesemia

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. 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. 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. Pretransplant hypomagnesemia is an independent risk factor of NODAT. Therefore, it is necessary to closely monitor the Mg levels in the posttransplant period.

New-onset diabetes after kidney transplantation: Incidence, risk factors, and outcomes.

Many patients develop new-onset diabetes after kidney transplantation (NODAT). Its incidence and epidemiology are unknown in the Saudi population. We aimed to study the incidence, epidemiology, and outcomes of kidney transplant recipients who developed NODAT. This is a retrospective study of all adults who received kidney transplant between January 2003 and December 2009. NODAT was defined according to the criteria outlined in the 2003 International Consensus guidelines. A total of 500 patients were included in this study, 54% were male patients. One hundred thirty-six patients (27%) developed diabetes (NODAT group). In the univariate analysis, patients were older in the NODAT group (P <0.001), were of higher weight (P = 0.006), and had positive family history of diabetes (P = 0.002). Similarly, more patients in this group had impaired glucose tolerance before transplant (P = 0.01) and history of hepatitis C infection (P = 0.005). In the multivariate analysis, older age [odds ratio (OR) 1.06], family history of diabetes (OR 1.09), hepatitis C infection (OR 1.92), and impaired fasting glucose (OR 1.79) were significant risk factors for the development of NODAT. Mortality was 6% in the NODAT group and 0.5% in the non-diabetic group had died (P <0.001). Graft survival was not different between the groups (P = 0.35). In conclusion, there is a significant risk of developing diabetes after renal transplantation. Patients are at higher risk if they are older, have a family history of diabetes, pre-transplant impaired fasting/random glucose, and hepatitis C virus infection.

New-onset diabetes after kidney transplant in children.

The development of new-onset diabetes after kidney transplantation (NODAT) is associated with reduced graft function, increased cardiovascular morbidity and lower patient survival among adult recipients. In the pediatric population, however, the few studies examining NODAT have yielded inconsistent results. Therefore, the true incidence of NODAT in the pediatric population has been difficult to establish. The identification of children and adolescents at risk for NODAT requires appropriate screening questions and tests pre- and post-kidney transplant. Several risk factors have been implicated in the pathogenesis of NODAT and post-transplant glucose intolerance, including African American race, obesity, family history of diabetes and the type of immunosuppressant regimen. Moreover, uremia per se results in a state of insulin resistance that increases the risk of developing diabetes post-transplant. When an individual becomes glucose intolerant, early lifestyle modification and antihyperglycemic measures with tailoring of the immunosuppressant regimen should be implemented to prevent the development of NODAT. For the child or adolescent with NODAT, antihyperglycemic therapy should be prescribed in order to achieve optimal glycemic control, ultimately reducing complications and improving overall allograft and patient survival. In this article, we review the risk factors, screening methods, diagnosis, management and outcome of children and adolescents with NODAT and post-kidney transplant glucose intolerance.

The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation

AimsTo evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT). MethodsWe 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. ResultsSeventeen 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 8.4mmol/L. The incidences of NODAT were 23.5%, 16.7%, 9.1%, and 0% for patients with IGT+1h-PG ≥8.4mmol/L,IGT+1h-PG <8.4mmol/L, NGT+1h-PG ≥ 8.4mmol/L, and NGT+1h-PG<8.4mmol/L, respectively. ConclusionsThe 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 8.4mmol/L plus NGT/IGT can be used to identify patients at intermediate and high risk of developing NODAT.

Validation of a Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation

OBJECTIVEIdentification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention.RESEARCH DESIGN AND METHODSWe previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0–1), intermediate (2, 3), or high (4–7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n = 792) to obtain better estimates for a prediction equation.RESULTSAlthough the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%.CONCLUSIONSA pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.

Response to Comment on: Chakkera et al. Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation. Diabetes Care 2011;34:2141–2145

Responding to our recent article in Diabetes Care (1), Valderhaug et al. (2) wrote that we underestimated the prevalence of pretransplant diabetes and the incidence of new-onset diabetes after kidney transplantation (NODAT) because of our diagnostic methods. We diagnosed diabetes pre- and posttransplant using the data available in our practice—prescribed therapy, fasting plasma glucose (FPG), and HbA1c—rather than the 2003 consensus criteria that include an oral glucose tolerance test (OGTT) but not HbA1c (3). This criticism reflects a controversy about diagnostic criteria that exists even in the absence of kidney …

Comment on: Chakkera et al. Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation. Diabetes Care 2011;34:2141–2145

We read with interest the article by Chakkera et al. (1), which presented a pretransplant risk score to help identify subjects who might develop new-onset diabetes after kidney transplantation (NODAT). Although the authors briefly discussed the limitations of their diagnostic criteria of NODAT, they did not elaborate on how the exclusion of an oral glucose tolerance test (OGTT) might impact the external validity and generalizability of the study. First, the authors documented the absence of diabetes before transplantation by assessing the forms submitted to the United Network for Organ Sharing. In addition, at pretransplant testing all patients had a fasting plasma glucose (FPG) <126 mg/dL (7.0 mmol/L) and a …