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Objective. The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes.Design. DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients). Thirty-six healthy subjects served as controls. Clinical characteristics (diabetes mellitus, nutritional status and presence of clinical CVD), inflammation and oxidative stress biomarkers, homocysteine and global DNA methylation in peripheral blood leucocytes (defined as HpaII/ MspI ratio by the Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients (n ¼ 98) starting dialysis treatment were followed for a period of 36 ± 2 months.Results. Inflamed patients had lower ratios of HpaII/ MspI, indicating global DNA hypermethylation. Analysis by the Cox regression model demonstrated that DNA hypermethylation (HpaII/MspI ratio

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Background: Adipose tissue in overweight patients with end-stage renal disease (ESRD) is a source of proinflammatory mediators, which could contribute to protein-energy wasting (PEW), cardiovascular disease, and increased mortality. Overweight in ESRD patients, however, is reported to be associated with better survival. Objective: We investigated the associations between overweight [body mass index (BMI; in kg/m 2 ) 25], inflammation, PEW, and mortality in ESRD patients starting dialysis. Design: In 328 ESRD patients (age: 53 Ȁ 12 y; 201 men), inflammatory biomarkers, nutritional status, and dual-energy X-ray absorptiometry data were analyzed close to the start of treatment. We compared clinical and laboratory data in patients in 3 BMI groups, with and without PEW. Results: The prevalence of PEW was high in patients in all 3 BMI groups. PEW was associated with both high fat body mass index (FBMI) and low lean body mass index (LBMI). Both PEW and high BMI were associated with inflammation. The highest concentrations of inflammatory mediators and the highest FBMI were seen in overweight patients with PEW. BMI as such did not predict clinical outcome; however, for each BMI group, the presence of PEW was associated with increased mortality. With BMI 20 -25 as the reference group, BMI 20 did not predict mortality, overweight (BMI 25) was associated with a survival advantage, and low FBMI was found to be an independent predictor of mortality. Conclusions: PEW is common in overweight ESRD patients and is associated with high FBMI, low LBMI, and inflammation. PEW was a predictor of mortality in both obese and nonobese sarcopenia patients. BMI as such, however, was a poor predictor of mortality, but after adjustment for various confounders, including PEW, a high BMI and a high FBMI were associated with survival advantage.Am J Clin Nutr 2007;86:633-8.

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Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in CKD patients.

Background and Objectives: Plasma protein pentraxin 3 concentrations are elevated in a wide range of diseased states. However, no study has evaluated protein pentraxin 3 in patients with chronic kidney disease.Design, Setting, Participants, & Measurements: Plasma protein pentraxin 3 concentrations were analyzed in relation to GFR, inflammation, cardiovascular disease, and protein-energy wasting in 71 patients with stages 3 to 4 chronic kidney disease, 276 patients with stage 5 chronic kidney disease, and 61 control subjects. Survival (5 yr) in patients with stage 5 chronic kidney disease was analyzed in relation to protein pentraxin 3 levels.Results: Both patient groups with chronic kidney disease had higher protein pentraxin 3 concentrations than control subjects, with the highest concentration in patients with stage 5 chronic kidney disease. In all patients with chronic kidney disease, protein pentraxin 3 correlated negatively with GFR and positively with inflammatory markers. Patients with protein-energy wasting, inflammation, and cardiovascular disease had higher concentrations of protein pentraxin 3 than their counterparts. Patients with high protein pentraxin 3 levels had higher all-cause and cardiovascular mortality. After adjustment for age, gender, C-reactive protein, and cardiovascular disease, all-cause mortality was still significantly higher in patients with high protein pentraxin 3. Finally, protein pentraxin 3 showed a predictive value of mortality similar to that of IL-6 and better than C-reactive protein.Conclusion: Plasma protein pentraxin 3 increases as GFR declines and is associated with the presence of cardiovascular disease and protein-energy wasting. Furthermore, in patients with chronic kidney disease, elevated protein pentraxin 3 predicted all-cause mortality.