The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD.

Aim CHA2DS2‐VASc and modified‐CHADS2 score can easily estimate the risk of stroke in atrial fibrillation. Study's purpose was to evaluate these in haemodialysis patients, and assess the effect of diabetes mellitus (DM). Methods The scores calculated in 237 haemodialysis patients, 121 diabetics (58 females) and 116 non‐diabetics (41 females). Results correlated to cardiovascular events (acute myocardial infarction, atrial fibrillation, heart failure, peripheral arterial disease, stroke, mortality). Results CHA2DS2‐VASc score correlated with the occurrence of stroke and heart failure (p < .01, p < .01), (p < .01, p < .01), respectively in diabetics and non‐diabetics. CHA2DS2‐VASc score could predict the risk of all‐cause mortality in both groups, p = .03, p < .01, respectively, however, the risk of cardiovascular death could be predicted in non‐diabetics, p < .01. Modified‐CHADS2 score associated with heart failure (p = .04), cardiovascular (p < .01) and all‐cause mortality (p < .01) only on non‐diabetics. C statistics indicated that the first score showed modest discrimination in patients with and without DM, for stroke and all‐cause mortality. The second score performed modestly only on patients without DM for all‐cause mortality. Both scores showed poor calibration. Stroke was a common cause of cardiovascular death (OR = 3.52, 95% CI = 1.92–6.47, p < .01) and associated with central venous catheter (OR = 2.19, 95% CI = 1.12–4.27, p = .02) and pre‐existing atrial fibrillation (OR = 1.94, 95% CI = 1.06–3.58, p = .03). Conclusion CHA2DS2‐VASc score correlated with stroke, heart failure and all‐cause mortality in haemodialysis patients with and without DM. The risk of cardiovascular death could be predicted only in non‐diabetics patients. Modified‐CHADS2 score correlated with heart failure, cardiovascular and all‐cause mortality only on non‐diabetics. Both had modest discrimination and poor calibration.

Background and Aims Hemodiafiltration (HDF) is characterized by enhanced clearance of middle molecular weight toxins and therefore, it is considered superior to hemodialysis (HD), especially in higher hemofiltration volumes. Although proinflammatory cytokines are lower in HDF, its impact on immune phenotype has not been studied, so far. In this study we compared the lymphocytes’ senescent phenotype between HD and HDF patients. Method Senescent and exhausted related lymphocyte markers, including CD45RA, CCR7, CD28, CD57 and PD1 on T cells and CD27 and IgD on B cells, were assessed by flow cytometry in 35 ESRD patients on HD and 25 ESRD patients on HDF of similar age, sex, and ethnicity. Moreover, we evaluated the association of these markers with hemofiltration volume. Results Patients on HDF had significantly reduced CD4+CD28- T lymphocytes, 31(18-74) vs 50(36-131)cells/μL, respectively, p = 0.019, which was restricted only in the CD28-CD57- T cells compartment, [17(9-25) vs 31(19-50)cells/μL, p = 0,002], while terminally differentiated CD28-CD57+ did not differ between the two groups [14(4-49) vs 23(7-52)cells/μL, p = 0,22]. Expression of CD57 molecule on CD4+ T cells depended on dialysis vintage (r = 0.27, p = 0.03). Moreover, HDF patients had lower percentage of CD4+PD1+ exhausted T cells [8.5(6.8-11.7) vs 13.7(8.7-19.5) % for HDF and HD respectively, p = 0.006]. CD8+PD1+ T cells were also lower in HDF patients, without reaching statistical significance [17.4(8.5-41) vs 34(12,7-52.9) % for HDF and HD respectively, p = 0.06]. Hemofiltration volume was negatively correlated to effector memory CD8+ T cells re-expressing CD45RA count (CD8+ EMRA), (r = -0.46, p = 0.027) and positively correlated to total B cells count (r = 0.46, p = 0.025). However, not all B cell subsets were equally affected, with only naïve IgD+CD27- B cells and switched memory IgD-CD27+ B cells count showing positive correlation with hemofiltration volume (r = 0.53, p = 0.008 and r = 0.5, p = 0.015, respectively). Conclusion Hemodiafiltration and high filtration volumes may have beneficial effects on adaptive immunity, predisposing to less senescent and exhausted T and B cell phenotypes.

Background and Aims Mortality in hemodialysis patients significantly exceeds the one observed in general population. Identifying and early management of risk factors is essential for improving survival of these patients. Aim of the study is to assess survival and evaluate factors related to mortality in hemodialysis population. Method We retrospectively studied 237 patients [99 ♀, median age 76 (69-84) years] undergoing hemodialysis in a single Dialysis Center for a 10-years period of time (from 1/2/2010 to 31/1/2021). Demographics, comorbidities and laboratory parameters were recorded and analyzed. Median survival, mortality rate and factors that may affect them were evaluated. Results The mortality rate was 9.28% in the first year and 36.29% in five years after starting dialysis, respectively (Figure 1. Kaplan-Meier survival curves for the study population). Elderly patients (&gt;65 years) had a lower median survival compared to younger ones (63 versus 103 months, p = 0.031). Survival of diabetics undergoing on-line hemodiafiltration was twice versus those undergoing hemodialysis (87 versus 42 months, p&lt;0.001). Most common causes of death were cardiovascular diseases (32.38%), infections (20.95%) and cancer (18.1%) (p&lt;0.001). Multivariate analysis identified as important predictors of mortality, the existence of: diabetes mellitus [hazard ratio (HR) = 2.387, 95% confidence interval (CI) 1.278-4.46, p = 0.006], peripheral arterial disease (HR = 1.875, 95% CI 1.12-3.139, p = 0.017) and central venous catheter (HR = 2.421, 95% CI 1.297-4.518, p = 0.005). In contrast, absence of vascular access thrombotic episode (HR = 0.289, 95% CI 0.158-0.527, p&lt;0.001) and body mass index &gt;20 kg/m2 (HR = 0.517, 95% CI 0.294-0.909, p = 0.022) had a favorable effect on survival. Conclusion Mortality rate in our cohort was measured 9.28% in first year and 36.29% in five years after starting hemodialysis. Survival was lower at elderly and diabetic patients undergoing hemodialysis. Our study identified some mortality factors potentially modifiable, such as body weight, type of vascular access and method of dialysis treatment.