Background. Left ventricular hypertrophy (LVH) is common in chronic kidney disease (CKD), including kidney transplant recipients. However, time-related left ventricular mass changes (▵LVM) from ...pre-dialysis stage to beyond the first post-transplant year have not been clearly identified. Methods. We studied a cohort of 60 stages 4–5 CKD patients without overt cardiac disease, who underwent three echocardiograms during follow-up: at pre-dialysis stage, on dialysis and after kidney transplantation (KT). Multiple linear regression was used to model ▵LVM from baseline study. Cox proportional analysis was used to determine risk factors associated with either de novo LVH or >20% ▵LVMI over time. Results. Patients with baseline LVH (n = 37; 61%) had a higher body mass index (BMI) than those without LVH (n = 23; 39%) (P = 0.013). BMI, haemoglobin levels (P = 0.047) and non-use of angiotensin-converting enzyme inhibitors (ACEI) (P = 0.057) were associated with baseline left ventricular mass index (LVMI). Twelve out of 23 patients (52%) with normal LVM at baseline, developed either de novo LVH or >20% ▵LVMI at follow-up. On the other hand, 29 (78%) of those with initial LVH maintained this abnormality, and 8 (22%) normalized LVM post-transplantation. Factors associated with ▵LVMI were age (P = 0.01), pre-dialysis LVMI (P < 0.0001), serum creatinine (P = 0.012) and the use of ACEI post-transplantation (P = 0.009). In Cox analysis, pre-dialysis LVMI was associated with de novo LVH or >20% ▵LVMI over time (hazard ratio 1.009; 95% confidence interval 1.004 to 1.015; P = 0.001). Conclusions. Successful KT may not completely normalize LVM post-transplantation. Pre-dialysis LVMI, traditional risk factors and no use of ACEI may perpetuate cardiac growth following KT.
Switching to cyclosporine A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown.
Obese Zucker rats were used as a ...model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3mg/kg/day) until diabetes development; then: (a)22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b)22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and were used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study.
β-cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day 12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day 12 group, rats in tacrolimus-cyclosporin group showed an increased β-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable.
An early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased β-cell proliferation and reversion of diabetes in 50% of cases.
Summary
Prolonged cold ischemia time (CIT) is associated with delayed graft function and worse kidney transplant (KT) outcome, but the effect of CIT on long‐term allograft survival in KT from younger ...donors has not been well established. We investigated the predictive value of CIT exposure on long‐term death‐censored graft loss in 829 KT recipients from younger donors (<50 years) that were performed in our center between 1991 and 2005. Overall death‐censored graft failure rate was significantly higher in CIT≥19 h group versus CIT<19 h group (26 vs. 16.5%; P = 0.002). Significant differences were also observed when patients with primary nonfunctioning graft were excluded (21 vs. 14%; P = 0.020) and in patients who received tacrolimus plus mycophenolate mofetil (12 vs. 4%; P = 0.05). By multivariate Cox analysis, CIT was found to be independently associated with death‐censored graft loss with a 20% increase for every 5 h of CIT relative risk (RR) 1.04; 95% Confidence Interval (CI): 1.01–1.1; P = 0.021. Likewise, graft loss risk significantly increased in CIT≥19 h group versus CIT<19 h group (RR 1.5; 95%CI: 1.1–2.1; P = 0.023). Prolonged CIT is an independent predictor of graft survival in KT from younger donors. Efforts at minimizing CIT (<19 h) should improve transplant outcome significantly in this population.
Insulin-resistance hyperinsulinemia is a novel risk factor for renal disease in the general population. Glomerular hyperfiltration has been proposed as an early consequence of hyperinsulinemia.
In ...this multicenter cohort study, we analyzed 202 patients without diabetes before or after renal transplantation during the first posttransplant year. Insulin was measured at 3 and 12 months. The majority of patients (91%) were on calcineurin inhibitors. Patients were classified as with persistent normo or hyperinsulinemia when situated below or above the median value of insulin (3 months: 9 muU/mL; 12 months: 8.74 muU/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3-12 months DeltaCrCL) was calculated.
Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months DeltaCrCL compared with those with persistent normoinsulinemia (12% -20/40 vs. -0.03% -12/18, P=0.035). We performed a multivariate linear regression analysis with the 3 to 12 months DeltaCrCL as the dependent variable and different factors that may induce hyperfiltration, including persistent hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor for increased CrCL (beta 0.09, 95% CI 0.07/0.12, P=0.035).
In nondiabetic recipients during the first posttransplant year, hyperinsulinemia induced increments in CrCL. As this may herald future renal dysfunction, hyperinsulinemia should not be ignored as a potential target in this population.
Prediabetic glucose homeostasis alterations are important cardiovascular risk factors but their role in renal transplant recipients (RTR) has not been established.
In 172 RTRs without pretransplant ...or de novo diabetes, we measured carotid intima media thickness (c-IMT) and performed an oral glucose tolerance test (OGTT).
In multivariate analysis, age, hypertension and male sex were independently associated with a c-IMT in the third tertile. A significant interaction between gender and glucose homeostasis parameters was observed. Among male RTR, those with a c-IMT in the third tertile showed significantly higher plasma glucose and HbA1c levels (5+/-0.5% vs. 5.1+/-0.5% vs. 5.5+/-0.4%; P<0.01 tertile 3 vs. 2 or 1) than those in other tertiles. Insulin action parameters were not significantly different. The odds ratio of being in the higher c-IMT tertile was 2.9 (95% CI: 1.05-8.1) per each 1% increase of HbA1c. By contrast, glucose and HbA1c levels were not significantly different between c-IMT tertiles in female RTR. However, age-adjusted insulin levels after OGTT were higher (86+/-10 vs. 51.7+/-9.4; P=0.02) and the insulin sensitivity index lower (0.8+/-0.3 vs. 0.048+/-0.03; P=0.04) among females in the third tertile as compared to the first one.
Prediabetic glucose homeostasis alterations in RTRs are related to carotid atherosclerosis, although there may be gender differences in the underlying alteration.
Background. C-reactive protein (CRP), a marker of chronic subclinical inflammation (CSI), is related to cardiovascular mortality in the general and renal transplant populations. In the general ...population, high CRP levels are associated with pre-diabetic glucose homeostasis alterations which may contribute to the proatherogenic effect of CSI. Methods. We studied 134 consecutive renal transplant recipients without pre-existing or new onset diabetes. CRP, oral glucose tolerance test, insulin sensitivity and HbA1c were measured. Results. Among CRP tertiles, fasting glucose and glucose after 120 min were not different. However, HbA1c was higher (4.9 ± 0.6; 5.2 ± 0.5; 5.4 ± 0.5; P = 0.005 and insulin sensitivity lower (McAuley index: 7.2 ± 2; 6.8 ± 2; 6.2 ± 1.3; P = 0.042) in the third CRP tertile. In addition, HDL-cholesterol was lower and triglycerides and body mass index (BMI) higher in the third tertile. Consequently, metabolic syndrome was more prevalent in the upper CRP tertiles 11 (25%); 19 (43%); 22 (50%); P = 0.01). In multivariate analyses, HbA1c was related to higher CRP levels (standardized β coefficient = 0.21, P = 0.013), independently of BMI (standardized β coefficient = 0.24, P = 0.005) and triglycerides (standardized β coefficient = 0.18; P = 0.03). Conclusions. Subclinical glucose homeostasis alterations are related to chronic inflammation in renal transplant recipients without pre-existing or new onset diabetes and may contribute to their high cardiovascular mortality.
Beekeepers around the world select bees' characteristics that facilitate and favor production. In regions where hybridization among lineages is taking place, this selection is a challenge, given that ...these regions are "natural laboratories", where the action of evolutionary processes of a population or species occurs in real time. A natural honeybee (
) hybrid zone exists in Argentina between 28° and 35° South, where Africanized (AHB) and European (EHB) populations converge. In this zone, beekeepers use selected genetic resources of European origin mostly, since the local Africanized bees show a higher defensive behavior, which is not desirable for management. Although EHB colonies have many advantages for honey production, they are not fully adapted to the subtropical climate and are susceptible to certain parasitosis such as varroosis. In addition, both AHB and EHB mate in drone congregation areas (DCAs), where males and virgin queens fly to meet, resulting in variability in the desired characteristics. In this study, we explored the degree of hybridization within a DCA and its reference apiary, located in the province of Entre Ríos, by applying two complementary techniques. First, morphotypes with different degrees of hybridization between European and African subspecies were observed in the reference apiary, indicating a high sensitivity of this morphometric approach to detect hybridization in these populations. Second, a genetic analysis revealed haplotypes of both origins for drones in DCAs, with a higher prevalence of European haplotypes, while all the colonies from the reference apiary exhibited European haplotypes. Overall, our results are in line with the strong impact that commercial beekeeping has on the genetics of DCAs. We show how wing morphometry may be used to monitor hybridization between European and African subspecies, a tool that may be evaluated in other regions of the world where hybridization occurs.
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