Study of the pathogenesis and progression of atherosclerotic vascular in uremic patients

Atherosclerotic cardiovascular disease is the main cause of the increased morbidity and mortality in patients with chronic kidney disease (CKD) and particularly in those on renal replacement therapy. Despite extensive investigation, the underlying mechanisms are not yet completely understood. However, it appears that the activation of the inflammatory response observed in uremia plays a major role in these processes. The aim of the present study was to investigate the probable associations between mediators of the inflammatory response and the extent and severity of the atherosclerotic vascular changes in patients with CKD-stage 5. Moreover, in a follow-up study, the associations between the above factors and the progression of atherosclerosis and the development of cardiovascular events were investigated. […]Οι ασθενείς µε χρόνια νεφρική νόσο (ΧΝΝ) και ιδιαίτερα εκείνων που υποβάλλονται σε θεραπεία υποκατάστασης της νεφρικής λειτουργίας εµφανίζουν πρώιµη και επιταχυνόµενη αθηροσκλήρωση που αποτελεί την κύρια αιτία της αυξηµένης νοσηρότητας και θνητότητάς τους. Παρά τις εκτεταµένες έρευνες, οι υποκείμενοι παθογενετικοί μηχανισμοί δεν είναι ακόµη πλήρως διευκρινισμένοι. Εν τούτοις, υπάρχει πλήθος δεδομένων που υποδηλώνουν ότι, η ενεργοποίηση της φλεγμονώδους αντίδρασης που χαρακτηρίζει τη χρόνια ουραιµία, παίζει σημαντικό ρόλο στις παραπάνω διεργασίες. Σκοπός της παρούσας µελέτης ήταν η διερεύνηση της ενδεχόµενης συσχέτισης µεσολαβητών της φλεγµονώδους αντίδρασης, µεταξύ των οποίων περιλαµβάνονταν κυτταροκίνες και µόρια προσκόλλησης των ενδοθηλιακών κυττάρων, µε την έκταση και τη βαρύτητα των αθηροσκληρωτικών αγγειακών αλλοιώσεων σε ασθενείς µε ΧΝΝ 5ου σταδίου υπό συντηρητική αγωγή ή υπό εξωνεφρική κάθαρση. Ακόµη, σε προοπτκή µελέτη, διερευνήθηκε η συσχέτιση των παραπάνω παραγόντων µε την εξέλιξη της αθηροσκλήρωσης, αλλά και την εµφάνιση καρδιαγγειακών συµβαµάτων, σε ασθενείς υπό εξωνεφρική κάθαρση. […

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave’s disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto’s thyroiditis two months post-vaccination. Grave’s disease is uncommon in dialysis patients, whereas Hashimoto’s thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD

Dysregulation of Plasma miR-146a and miR-155 Expression Profile in Mycosis Fungoides Is Associated with rs2910164 and rs767649 Polymorphisms

Diagnosis of Mycosis Fungoides (MF) may be challenging, due to its polymorphic nature. The use of miRNAs as biomarkers to assist in diagnosis has been investigated, mainly in skin lesion biopsies. The purpose of this study is to evaluate the plasma levels of miR-146a and miR-155 in MF patients and to investigate their association with SNPs of their genes. Plasma miRNAs were quantified by RT-qPCR. Genomic DNA was used for SNPs’ genotyping by Sanger sequencing. Plasma levels of miR-146a and miR-155 were significantly higher in patients vs. controls, in early MF patients vs. controls, and in advanced vs. early MF patients. Both miRNAs’ levels were significantly higher in stage IIB vs. early-stage patients. miR-155 plasma levels were significantly higher in patients with skin tumors or erythroderma. CC genotype (rs2910164 C>G) was significantly more frequent in healthy controls and associated with lower MF risk and lower miR-146a levels. The AA genotype (rs767649 T>A) was significantly more frequent in patients and correlated with increased MF risk and increased miR-155 levels. The combination of GG+AA was only detected in patients and was correlated with higher MF susceptibility. Increased mir-146a and mir-155 plasma levels in MF is an important finding to establish putative noninvasive biomarkers. The presence of SNPs is closely associated with miRs’ expression, and possibly with disease susceptibility

Heart rate variability at rest and in response to stress: Comparative study between hemodialysis and peritoneal dialysis patients.

Cardiac arrhythmias and sudden death are the leading causes of mortality in end-stage kidney disease (ESKD). Autonomic nervous system (ANS) dysfunction contributes to this arrhythmogenic background. This study compared heart rate variability (HRV) indices between hemodialysis (HD) and peritoneal dialysis (PD) patients, both at rest and in response to mental and physical stimulation maneuvers. Thirty-four HD and 34 PD patients matched for age, sex, and dialysis vintage, and 17 age- and sex-matched controls were studied. ANS function was examined by linear and non-linear HRV indices. Heart rate was recorded continuously (Finometer-PRO) at rest and during ANS maneuvers (orthostatic, mental-arithmetic, sit-to-stand, handgrip exercise tests). At rest, no significant differences between HD and PD were observed in HRV (root mean square of successive differences [RMSSD]: HD = 57.1 ± 81.1 vs PD = 69.6 ± 113.4 ms; = 0.792), except for detrended fluctuation analysis (DFA-α1) (HD = 0.87 ± 0.40 vs PD = 0.70 ± 0.20; = 0.047). DFA-α1 was significantly lower in PD than controls (1.00 ± 0.33; < 0.05). All HRV indices during the mental-arithmetic test (RMSSD: HD = 128.2 ± 346.0 vs PD = 87.5 ± 150.0 ms; = 0.893) and the physical stress tests were similar between HD and PD. The standard deviation along the line-of-identity (SD2)/the standard deviation perpendicular to the line-of-identity (SD1) ratio during mental-arithmetic was marginally lower in HD and significantly lower in PD than controls (PD = 1.31 ± 0.47 vs controls = 1.79 ± 0.64; < 0.05). Both dialysis groups presented similar patterns in HRV responses during orthostatic and handgrip exercise tests. After the sit-to-stand, RMSSD, SD1, SD2, and DFA-α2 were higher compared to rest only in HD (RMSSD = 57.1 ± 81.1 vs 126.7 ± 185.7 ms; = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function in response to physical stress. In conclusion, HRV indices at rest and after mental and physical stimulation did not differ between HD and PD; however, the ANS responses following the sit-to-stand test were more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality, but small differences in normal ANS recovery may exist