Early Pulse Pressure and Low-Grade Proteinuria as Independent Long-Term Risk Factors for New-Onset Diabetes Mellitus After Kidney Transplantation

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts.
We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Causasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years).
The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25–3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32–3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07–3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03–1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12–1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg.
Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.     

Risk Factors for Depression After Kidney Transplantation

Objective

Kidney transplantation is recognized as the only potentially curative treatment for end-stage renal failure. But many psychiatric problems are associated with the procedure. The purpose of this study was to identify predictors of a risk for depression after kidney transplantation.

Materials and Methods

This retrospective cohort study recruited 116 first kidney-only Japanese recipients whose mean age was 50.2 ± 11.87 years include a male/female ratio of 63/53. They underwent transplantation between 1990 and 2008. At enrollment, we used the Zung Self-rating Depression Scale score as well as characterized demographic and clinical features of recipients and donors. Comparisons between depressed and non-depressed patients concerning sociodemographic and clinical characteristics were used χ² tests for categorical variables and Student's t-tests for continuous variables. Risk factors with significant correlation coefficients (P < .05) were entered into a stepwise logistic regression model to identify the best single risk factor for depression after kidney transplantation.

Result

The prevalence of depression in this study was 41.4%. Depressed patients were significantly more likely to not have regular incomes, nor to have desired kidney transplantation, to have experienced a rejection episode, and to live alone (P < .05). The single best predictor of future depression was living alone; subjects living alone were 2.51 times more likely to be depressed as those living with others (adjusted odds ratio [OR], 2.51; 95% confidence interval [CI], 1.31-5.22; P < .05).

Conclusion

Although depression after kidney transplantation is driven by multiple, complex, and often overlapping risk factors, we observed characteristic features of recipients including their social environment and follow-up treatment.     

Risk Factors for New-Onset Diabetes Mellitus After Heart Transplantation: A Nomogram Approach

BackgroundNew-onset diabetes mellitus after transplantation (NODAT) is a leading cause of morbidity and mortality after heart transplantation (HT), which still remains a clinical challenge.MethodsIn this study, 522,708 follow-up records of HT were reviewed. After screening, 14,452 patients were analyzed when combined with immunosuppression records. We divided all patients into no-NODAT group, NODAT group, and preexisting diabetes group based on whether the patient had diabetes and the time when it occurred. Cox regression models were used to examine independent risk factors. A nomogram was established to predict the incidence of NODAT after HT. The machine learning method were used to confirm the prediction accuracy and reliability of the nomogram.ResultsPatients who experienced NODAT after HT had poor survival compared with those without NODAT. Tacrolimus, cyclosporine A (CsA), rapamycin, donor age, and recipient age at the time of transplant were significant predictors of NODAT. Tacrolimus had a more significant association with NODAT, followed by rapamycin and CsA. The nomogram method we adopted in this study had an accuracy of 63% in predicting the incidence of NODAT.ConclusionThe survival probability of HT recipients with NODAT showed a significant decreasing tendency. However, there was no difference in survival probability between patients with preexisting diabetes and patients with NODAT. Tacrolimus had a more significant association with NODAT than CsA and rapamycin.     

Risk Factors for Development of New-Onset Diabetes Mellitus and Progressive Impairment of Glucose Metabolism After Living-Donor Liver Transplantation

Background

New-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients.

Methods

We collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined.

Results

Pre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes.

Conclusions

Older age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.     

Obesity Risk Factors in Patients After Kidney Transplantation

Background

Kidney transplantation is currently the best approach for renal replacement therapy. Compared with dialysis, it provides a better quality of life and improves patient prognosis. However, some evidence suggests that body composition could play a role in the complications observed in kidney transplant recipients (KTRs), and may influence survival. The purpose of this study was to assess the eating habits and body composition of KTRs.

Diabetes Mellitus as Predictor of Patient and Graft Survival After Kidney Transplantation

Background

In this study, we used a single-center database to examine the risks of renal transplantation in patients with diabetes mellitus (DM). We aimed to compare 1-year outcomes of survival and morbidity after renal transplantation among recipients with and without DM.

Methods

We reviewed retrospectively 1211 adult patients who underwent renal transplantation from January 2001 to December 2010. The patients were divided into 2 groups: Those with (33%) and those without (67%) pretransplant diabetes. Unpaired Student's t tests and χ² tests were used to compare outcomes between diabetic and nondiabetic renal transplant recipients. We analyzed survival, renal function, development of proteinuria, rejection, and infection (requiring hospitalization).

Results

Patients with diabetes were older, had a greater body mass index (mean, 29.5 vs 25.3 kg/m²; P < .05), and had lower creatinine clearance (44.2 ± 11.4 vs 56.0 ± 18.2; P = .01). Forty-one patients died in hospital (3.4%; P = nonsignificant). Furthermore, survival rates were similar between these 2 groups. However, we found a trend toward decreased survival for those with DM at 1 year (80.4% vs 88.7%; P = .20). Mean follow-up time was 3.2 years. Infection rate within 6 months was greater among those with DM (19% vs 5%; odds ratio, 6.25). Freedom from rejection at 3 years was similar (75.2% vs 76.8%; P = .57). Multivariate analysis showed increased baseline creatinine level as a significant risk factor for survival. Body mass index >30 kg/m² was a significant risk factor for survival among patients with DM.

Conclusion

We found an increased risk of serious infections in patients with DM, particularly within the first 6 months. However, our data suggest that diabetes is not associated with worse 1-year survival or higher morbidity in renal transplant patients, as long as good blood glucose control is maintained.     

Clinical Consequences of Diabetes Mellitus in Patients After Kidney Transplantation: A Paired Kidney Analysis

Background

Diabetes mellitus (DM) has been acknowledged as the most common disorder leading to end-stage renal failure in adults. Diabetic patients show higher survival rates after kidney transplantation (KTx) compared with dialysis therapy. The aim of the study was to evaluate follow-up after KTx in patients with DM as a reason of end-stage renal disease (ESRD), or with long-lasting diabetes before transplantation, compared with patients without DM.

Posttransplant Diabetes Mellitus After Pancreas Transplantation

Some patients do not achieve normoglycemia after an otherwise successful pancreas transplant. The aim of this study was to define the incidence and risk factors for the development of persistent diabetes mellitus after pancreas transplantation. We studied the outcomes of 144 pancreas transplants performed at our institution between January 2001 and December 2005. Diabetes mellitus was defined as the persistent need for pharmacologic treatment of diabetes mellitus despite evidence of allograft function. Data are expressed as median (25–75% inter-quartile range). Median follow-up was 39 months (IQR 26–55 months). During the follow-up period, 28 patients (19%) developed diabetes mellitus with a functioning allograft. Factors predicting hyperglycemia included: pretransplant insulin dose, BMI and acute rejection episodes (p < 0.0001, p = 0.0002 and p < 0.02, respectively). The median pretransplant hemoglobin A1c for patients developing diabetes was 8.3% (IQR 7.0–9.4%) compared to 6.2% (IQR 5.8–7.4%) at 2 years after transplant (p = 0.0069). In conclusion, persistent diabetes mellitus can occur despite the presence of a functioning pancreas allograft and is due to increased pretransplant BMI, high pretransplant insulin requirements and episodes of acute rejection.     

Early Steroid Withdrawal After Kidney Transplantation in Patients at Risk for New-Onset Diabetes After Transplantation

BackgroundNew-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation because of worse graft survival and increased risk of cardiovascular events. It is partly induced by immunosuppressive therapies such as corticosteroids. This study aimed to assess whether early corticosteroid withdrawal on day 4 (early steroid withdrawal [ESW] group) could prevent the development of NODAT within 2 years posttransplantation while maintaining good graft and patient survival rates.MethodsThis was an observational, single-center, retrospective study. All patients received an induction therapy of antithymocyte globulin or basiliximab and maintenance therapy of tacrolimus/mycophenolate mofetil/corticosteroids. Patients were either weaned off corticosteroids on day 4 (ESW group) or were maintained on corticosteroids for at least 3 months (standard group). NODAT was defined as the initiation of any oral hypoglycemic agent or insulin at 3 months and up to 2 years posttransplantation in previously nondiabetic recipients.ResultsBetween January, 1, 2010, and December 14, 2014, 492 recipients were included in this study; 88 received the ESW strategy, and 404 received the standard strategy. Age and body mass index (BMI) were significantly higher in the ESW group. The incidence of NODAT was 36.8% in the ESW group and 8.8% in the standard group (odds ratio [OR], 47.5; P < .001). Compared with a matched sample from the standard group that had the same probability to benefit from ESW at baseline, ESW was still associated with a significantly increased risk of NODAT (OR, 4.41; P = .018). Among recipients with a BMI >25 kg/m², the ESW strategy significantly decreased the risk of NODAT compared with the standard strategy (OR, 0.07; P = .013). Safety endpoints (eg, acute rejection, de novo–specific antibodies, graft function/survival) did not differ between groups.ConclusionDespite a reassuring safety profile, ESW on day 4 after kidney transplantation only had a marginal effect on the incidence of NODAT.     

Development of Diabetes Mellitus Following Kidney Transplantation: A Canadian Experience

The onset of diabetes mellitus following kidney transplantation or post-transplant diabetes mellitus (PTDM) is now recognized as being an increasingly common complication that is associated with poor graft and patient survival. The incidence and clinical correlates of PTDM in a Canadian kidney transplant population has not been examined and may vary based on differences in demographics (i.e. race). Furthermore, little information exists on the association of variables such as cumulative dose of corticosteroids and trough calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney transplant in our center between 1995 and 2001 and found an overall PTDM rate of 9.8%. Five clinical factors were independently associated with PTDM: older recipient age, deceased donor, hepatitis C antibody status, rejection episode and use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose and calcineurin inhibitor trough level were not associated with PTDM. This study demonstrates that in a Canadian kidney transplant population that there is a significant risk of PTDM following kidney transplantation, and it is therefore advisable to minimize this risk.     

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)², and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.     

Incidence of Post-transplantation Diabetes Mellitus Within 1 Year After Kidney Transplantation and Related Factors in Korean Cohort Study

BackgroundPost-transplantation diabetes mellitus (PTDM) is associated with a higher risk of mortality and graft loss. The reported incidence of PTDM after kidney transplantation (KT) varies from 10% to 74% and varies by country and ethnicity. There are few reports of nationwide cohort studies on PTDM incidence and related factors in Korea. The purpose of this study was to evaluate incidence of PTDM and related factors within 1 year after KT in Korea.MethodsThe KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) enrolled 1080 recipients from July 2012 to August 2016. This study included 723 recipients, excluding 273 patients with pretransplant DM and 84 patients who were lost from follow-up within 1 year after KT.ResultsAmong 723 recipients, 85 (11.8%) recipients were diagnosed and treated with PTDM. Recipient age, HLA mismatches, hemoglobin A1c (HbA1c), waist-hip ratio (WHR), and use of prednisolone were significantly higher in PTDM group than the nondiabetic group. In the multivariable logistic regression analysis, independent risk factors for PTDM were older recipient age, higher WHR, and HbA1c before KT.ConclusionThe incidence of PTDM was 11.8% in a nationwide Korean cohort study. The factors related to the development of PTDM within 1 year after KT were older recipient age and higher WHR, and HbA1c levels before KT. In recipients with high WHR, it is important to control pretransplant abdominal obesity to prevent PTDM after KT.     

Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

Introduction

New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu.

Methods

We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT.

Results

The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT.

Conclusions

These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.     

Preoperative Risk Factors Associated With Urinary Complications After Kidney Transplantation

Background

Only surgically irrelevant risk factors including sex, African-American ancestry, or exceptional U-stitch anastomosis have been identified to associate with urinary complications after kidney transplantation. The objective was to identify modifiable and nonmodifiable risk factors associated with urinary complications after kidney transplantation.

Diabetes Mellitus after Kidney Transplantation in the United States

New onset diabetes is a major complication after kidney transplantation. However, the incidence, risk factors and clinical relevance of post-transplant diabetes mellitus (PTDM) vary among reports from single-center observational studies and clinical trials. Using data from the United Renal Data System we identified 11 659 Medicare beneficiaries who received their first kidney transplant in 1996-2000. The cumulative incidence of PTDM was 9.1% (95% confidence interval = 8.6-9.7%), 16.0% (15.3-16.7%), and 24.0% (23.1-24.9%) at 3, 12, and 36 months post-transplant, respectively. Using Cox's proportional hazards analysis, risk factors for PTDM included age, African American race (relative risk = 1.68, range: 1.52-1.85, p < 0.0001), Hispanic ethnicity (1.35, range: 1.19-1.54, p < 0.0001), male donor (1.12, range: 1.03-1.21, p = 0.0090), increasing HLA mismatches, hepatitis C infection (1.33, range: 1.15-1.55, p < 0.0001), body mass index >or=30 kg/m2 (1.73, range: 1.57-1.90, p < 0.0001), and the use of tacrolimus as the initial maintenance immunosuppressive medication (1.53, range: 1.29-1.81, p < 0.0001). Factors that reduced the risk for PTDM included the use of mycophenolate mofetil, azathioprine, younger recipient age, glomerulonephritis as a cause of kidney failure, and a college education. As a time-dependent covariate in Cox analyses that also included multiple other risk factors, PTDM was associated with increased graft failure (1.63, 1.46-1.84, p < 0.0001), death-censored graft failure (1.46, 1.25-1.70, p < 0.0001), and mortality (1.87, 1.60-2.18, p < 0.0001). We conclude that high incidences of PTDM are associated with the type of initial maintenance immunosuppression, race, ethnicity, obesity and hepatitis C infection. It is a strong, independent predictor of graft failure and mortality. Efforts should be made to minimize the risk of this important complication.     

Obesity, Adiponectin and Inflammation as Predictors of New-Onset Diabetes Mellitus After Kidney Transplantation

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.     

Analysis of Risk Factors for Delayed Graft Function After Kidney Transplantation

BackgroundDelayed graft function (DGF) is a serious complication associated with worsening outcomes in kidney transplantation. To facilitate DGF risk reduction, this study aimed to identify the incidence and modifiable risk factors of this condition in kidney transplant patients.MethodsThis retrospective chart review included 220 patients who underwent kidney transplants between 2012 and 2021 at our kidney transplant center. Delayed graft function was defined as the requirement of hemodialysis within a week of transplantation. Clinical data from patients with DGF and those without this condition were compared to identify risk factors of DGF.ResultsOf 205 eligible patients, 20 (9.76%) developed DGF. In the univariate analysis, high hemoglobin level, deceased-donor type, and longer warm and cold ischemic times were significantly associated with DGF (P < .05). In the variable selection in logistic regression analysis, high hemoglobin level, with a cutoff value of 11.35 g/dL, and deceased-donor transplants were associated with higher DGF incidence (P < .05 for both factors).ConclusionsOur findings newly demonstrated that DGF occurred more frequently in patients with hemoglobin level >11.35 g/dL. As such, improvement in kidney transplantation outcomes could be achieved by reducing this modifiable risk factor.     

Insulin Resistance as a Risk Factor for New-Onset Diabetes After Kidney Transplantation

Introduction

New-onset diabetes after transplantation (NODAT) is a serious and common complication after kidney transplantation. Insulin resistance, together with β-cell dysfunction, plays an essential role in the development of diabetes. Homeostasis model assessment of insulin resistance (HOMA-IR), which is calculated as [fasting plasma glucose (mmol/L) × fasting insulin (mU/L)]/22.5, is widely used as an index of insulin resistance. However, the correlation between pretransplant HOMA-IR and the development of NODAT has not been fully established.

Methods

We performed a retrospective study of 44 nondiabetic patients who underwent living donor kidney transplantation in our hospital from July 2006 to October 2009. We compared the HOMA-IR and demographic variables of patients who developed NODAT with those who did not.

Results

Five patients (11.4%) developed NODAT within 3 years after transplantation. There were no differences in demographic variables between patients who developed NODAT and those who did not. Logistic regression analysis revealed that HOMA-IR was a predictive factor of NODAT (odds ratio, 2.88; 95% CI, 1.11–9.59; P < .05).

Conclusions

Our results indicate that high HOMA-IR might be an important predictive factor for NODAT. These findings underline the importance of routine pretransplant measurements of fasting plasma glucose and serum insulin for evaluating HOMA-IR.