Background and objectivesDespite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients.Design, setting, participants, & measurementsWe included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points.ResultsDuring median follow-up of 5.4 (interquartile range, 4.9–6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently.ConclusionsAdherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.

OBJECTIVE Posttransplantation diabetes mellitus (PTDM) contributes to risk for cardiovascular morbidity and mortality in renal transplant recipients (RTRs). In the general population, consumption of a diet containing few fruits and vegetables predisposes to type 2 diabetes. The role of diet as a potential modifiable risk factor for PTDM has not been explored. Our focus was to investigate the prospective associations of fruit and vegetable intake with risk of PTDM in stable RTRs. RESEARCH DESIGN AND METHODS We included 472 adult RTRs who had a functioning graft ≥1 year. Fruit and vegetable intake was assessed by using a 177-item food frequency questionnaire. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. RESULTS During 5.2 years of follow-up, 52 RTRs (11%) developed PTDM. Fruit intake was not associated with PTDM (hazard ratio [HR] 0.90 [95% CI 0.79–1.03] per 2log g/day; P = 0.13), whereas vegetable intake was inversely associated with PTDM (HR 0.77 [95% CI 0.63–0.94] per 2log g/day; P = 0.009). Mediation analyses revealed that ±50% of the association between vegetable intake and PTDM was mediated by variations in key components of the metabolic syndrome (i.e., HDL cholesterol, triglycerides, and waist circumference) as determined by the National Cholesterol Education Program’s Adult Treatment Panel III Expert Panel. CONCLUSIONS In this study vegetable intake, but not fruit intake, was associated with lower risk of PTDM in RTRs, likely largely through beneficial effects on key components of the metabolic syndrome. These findings further support accumulating evidence that supports a recommendation of higher vegetable intake by RTRs.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. It is widely accepted that oxidative stress plays a key role in their development and progression; hence oxidative damage might be abrogated by antioxidants. Polyphenols are phytochemicals showing extensively studied antioxidant properties in-vivo. Most representative sources of these compounds include fruits, greens, nuts, herbs, cocoa, tea and coffee. Epidemiological evidence suggests an association between the consumption of polyphenol-rich vegetables and the reduction of cardiovascular disease prevalence. This fact could be related to the anti-inflammatory, antithrombotic and vasodilatory effects of polyphenols. Even though these biological effects could be mainly attributed to the antioxidant activity of polyphenols, other pharmacological mechanisms should also be considered. The latter could comprise direct anti-inflammatory effects, modulation of intracellular signaling and gene expression, improvement of nitric oxide homeostasis, as well as platelet antiaggregation. However, it is noticeable that protocols of interventions to evaluate the properties of polyphenols have failed to show the same positive results reported from observational studies. At present, a controversy exists regarding the actual effectiveness of polyphenols in preventing cardiovascular diseases. Therefore, an improvement of the available knowledge about polyphenol pharmacokinetics, together with a better understanding of the mechanisms of action of these compounds, could be of great benefit. Thus, a rational support for the development of interventional designs could provide reliable evidence on the actual role of polyphenols in CVD prevention.

10 (4) Systolic blood pressure, mm Hg 134 AE 17 136 AE 16 137 AE 19 0.18 Diastolic blood pressure, mm Hg 83 AE 11 83 AE 11 82 AE 11 0.60 Use of antihypertensive medication 187 (84) 197 (89) 208 (92) 0.02 Dietary intake Total energy intake, kcal/d 2259 AE 633 2088 AE 634 2152 AE 587 0.45 Cereals, g/d 187 (147-231) 176 (146-211) 178 (138-212) 0.21 Potatoes, g/d 111 (70-146) 118 (73-166) 122 (76-173) 0.29 Vegetables, g/d 80 (56-116) 80 (48-124) 75 (53-107) 0.54 Fruits, g/d 100 (48-189) 110 (53-197) 104 (39-186) 0.22 Legumes, g/d 29 (14-48) 30 (18-45) 31 (17-43) 0.88 Nuts, g/d 5.

Background and objectivesIn kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.Design, setting, participants, & measurementsProspective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε-[Carboxymethyl]lysine (CML) and Nε-[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes’s procedure.ResultsWe included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality.ConclusionsIn stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3

In RTRs, a relatively higher vegetable consumption is independently and strongly associated with lower cardiovascular mortality. A relatively higher fruit consumption is also associated with lower cardiovascular mortality, although particularly in RTRs with eGFR > 45 mL/min/1.73 m2 or an absence of proteinuria. Further studies seem warranted to investigate whether increasing consumption of fruits and vegetables may open opportunities for potential interventional pathways to decrease the burden of cardiovascular mortality in RTRs.

Background: Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a β-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the β-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo. Methods/design: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing.

Introduction Uric acid has gained considerable attention as a potential neuroprotective agent in stroke during the last decades, however, its role in the pathophysiology of ischemic stroke remains poorly understood. A serial evaluation of uric acid levels during the acute phase of stroke and its association with infarct size on magnetic resonance imaging is lacking. Methods We present a cohort study of 31 patients with ischemic stroke who were not candidates for thrombolysis according to current criteria at the time. We performed daily measurements of serum uric acid and total antioxidant capacity of plasma during the first week after symptoms onset and 30 days after. Infarct size was determined in the acute phase by a DWI sequence and the final infarct size with a control MRI (FLAIR) at day 30. Results Uric acid significantly decreases between days 2 to 6 compared to day 1, after adjustment by sex, age and DWI at diagnosis, with a nadir value at 72h. A mixed model analysis showed a negative association between DWI at diagnosis and uric acid evolution during the first week after stroke. Moreover, multivariable linear regression of uric acid values during follow up on DWI volumes demonstrated that DWI volume at diagnosis is negatively associated with uric acid levels at day 3 and 4. There were no significant associations between total antioxidant capacity of plasma and DWI at diagnosis, or FLAIR at any point. Discussion Patients with larger infarcts exhibited a significant decrease in serum uric acid levels, accounting for a more prominent reactive oxygen species scavenging activity with subsequent consumption and decay of this antioxidant. The different kinetics of total antioxidant capacity of plasma and serum uric acid levels suggests a specific role of uric acid in the antioxidant response in ischemic stroke.