Background and Objectives: Subclinical atherosclerosis, reflected by abnormal carotid intima–media thickness (cIMT), is pervasive among chronic kidney disease patients on chronic renal replacement ...therapy (RRT), being mostly influenced by uremia-related rather than traditional risk factors. Materials and Methods: In this pilot study, we measured circulating levels of Omentin-1, a recently discovered adipokine with strong anti-atherogenic properties, in a heterogeneous cohort of 77 asymptomatic RRT individuals (40 chronic kidney transplant recipients, Ktx; and 37 chronic hemodialysis patients, HD) and in 30 age-matched controls. Results: Omentin-1 was increased in RRT individuals as compared with controls (p = 0.03). When stratifying for renal replacement modality, we found Ktx patients to have significantly lower Omentin-1 than HD patients (p = 0.01). Lower Omentin-1 levels were also found among RRT individuals with pathological cIMT (168.7 51.1–457.8 vs. 474.9 197.2–1432.1; p = 0.004). Our multivariate correlations analysis revealed Omentin-1 as the most robust independent predictor of carotid atherosclerosis (β-0.687; p = 0.03), even more than total cholesterol, diastolic BP and age, and this adipokine was at the crossroad of a complex interplay with sustained inflammation (high CRP and ferritin) and hyperphosphatemia in predicting higher cIMT values. Conclusion: The findings reported extend to renal patients with advanced disease, with the possible involvement of Omentin-1 in the pathogenesis of atherosclerosis. This may set the stage for future interventional studies of Omentin-1 replacement to retard atherosclerosis progression, as it is currently being investigated in other disease settings.
In kidney transplantation (Ktx) recipients, cardiovascular (CV) disease remains the leading cause of death. Abnormal carotid intima-media thickness (IMT) represents a valid indicator of incipient ...atherosclerosis also in this setting. Cathepsin-K (CatK) is a cysteine protease involved in vascular remodelling, as well as in progressive atherosclerosis. In this study we evaluated clinical predictors of CatK in Ktx recipients, with a particular focus on its possible relationships with subclinical atherosclerosis.BackgroundIn kidney transplantation (Ktx) recipients, cardiovascular (CV) disease remains the leading cause of death. Abnormal carotid intima-media thickness (IMT) represents a valid indicator of incipient atherosclerosis also in this setting. Cathepsin-K (CatK) is a cysteine protease involved in vascular remodelling, as well as in progressive atherosclerosis. In this study we evaluated clinical predictors of CatK in Ktx recipients, with a particular focus on its possible relationships with subclinical atherosclerosis.Circulating CatK was measured in 40 stable Ktx recipients together with several laboratory, clinical and echocardiography parameters. 30 healthy subjects and 30 hemodialysis (HD) patients served as controls for CatK values. Carotid IMT was measured in Ktx and these subjects were then categorized according to age-gender reference cut-offs of normal IMT.MethodsCirculating CatK was measured in 40 stable Ktx recipients together with several laboratory, clinical and echocardiography parameters. 30 healthy subjects and 30 hemodialysis (HD) patients served as controls for CatK values. Carotid IMT was measured in Ktx and these subjects were then categorized according to age-gender reference cut-offs of normal IMT.CatK levels were similar in Ktx recipients and healthy subjects but significantly reduced as compared to HD (p = 0.0001). In Ktx, at multivariate analyses CatK was associated with the LV end-diastolic volume (LVEDVi) ( β = 0.514; p = 0.05), Ktx vintage ( β = -0.333; p = 0.05) and mean IMT ( β = -0.545; p = 0.05); this latter robust inverse association was confirmed also in another multivariate model with IMT as the dependent variable. Logistic regression analyses confirmed the beneficial meaning of CatK increase towards subclinical atherosclerosis Odds Ratio (OR) 0.761; 95% Confidence Interval (CI) 0.569-0.918, p = 0.04. At Receiver Operating Characteristics (ROC) analyses, CatK held a remarkable discriminatory power in identifying Ktx patients with abnormally increased IMT Area Under the Curve (AUC) 0.763; 95% CI 0.601-0.926; p = 0.001).ResultsCatK levels were similar in Ktx recipients and healthy subjects but significantly reduced as compared to HD (p = 0.0001). In Ktx, at multivariate analyses CatK was associated with the LV end-diastolic volume (LVEDVi) ( β = 0.514; p = 0.05), Ktx vintage ( β = -0.333; p = 0.05) and mean IMT ( β = -0.545; p = 0.05); this latter robust inverse association was confirmed also in another multivariate model with IMT as the dependent variable. Logistic regression analyses confirmed the beneficial meaning of CatK increase towards subclinical atherosclerosis Odds Ratio (OR) 0.761; 95% Confidence Interval (CI) 0.569-0.918, p = 0.04. At Receiver Operating Characteristics (ROC) analyses, CatK held a remarkable discriminatory power in identifying Ktx patients with abnormally increased IMT Area Under the Curve (AUC) 0.763; 95% CI 0.601-0.926; p = 0.001).In Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.ConclusionsIn Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.
Purpose
Cardiovascular (CV) disease remains the leading cause of mortality among end-stage kidney disease (ESKD) patients. Cathepsin-K (CatK), a small cysteine protease involved in bone and ...extracellular matrix remodeling, has recently emerged as a key-factor in the pathogenesis of various conditions predisposing to CV disease, including atherosclerosis, obesity, diabetes, and vascular calcification. In this pilot prospective study, we aimed at evaluating the clinical significance and the predictive power of CatK in a small cohort of hemodialysis (HD) patients.
Methods
Cathepsin-K was measured in 54 prevalent HD patients and in 30 controls together with routine parameters. Patients were then followed up to 26 months and the time of cardiovascular death (endpoint of the study prospective phase) recorded.
Results
CatK levels were increased in the HD cohort as compared with controls (
p
< 0.001). In HD patients, CatK was also independently correlated to PTH (
β
= 0.368;
p
= 0.001), alkaline phosphatase (
β
= 0.383;
p
< 0.001), C-reactive protein (
β
= 0.260;
p
= 0.01), and white cell count (
β
= − 0.219;
p
= 0.02). After baseline assessment, patients were followed for CV death (mean follow-up 24.8 ± 3.1 months). Kaplan–Meier analysis showed a worsen survival (log-rank
p
= 0.04) in HD patients with CatK levels > 440 pg/mL (best ROC-derived cut-off with 69.6% sensitivity and 79.8% specificity) with a crude HR (Mantel–Haenszel) of CV death of 3.46 (95% CI 1.89–13.44).
Conclusions
In prevalent HD patients, altered CatK levels may reflect mineral dysmetabolism and inflammation, and predict CV death in the mid-term. These preliminary findings prompt the rationale for further investigations on larger cohorts to validate CatK as a biomarker for improving CV risk stratification in ESKD.
SARS-CoV-2 is a betacoronavirus, which induced a severe pandemic infectious disease around the world. Even if several drugs have been suggested for its treatment, to date, the only strategy to reduce ...the severity of disease is represented by the use of vaccine. However, the lack of pre-marketing evidence in frail patients suggests the necessity of the real-world study of a vaccine benefit–risk profile. In this study, we evaluated the efficacy and the safety of SARS-CoV-2 vaccination in a cohort of 33 patients treated with an immunosuppressant after solid organ transplant. Both CLIA and LS/MS analysis were used to evaluate the levels of immunoglobulin (Ig)G anti SARS-CoV-2 and the therapeutic drug monitoring of immunosuppressant drugs. We documented that SARS-CoV-2 vaccination induced a dose- and gender-related serological response. In particular, in 63.6% of the enrolled patients, we documented a significant serological response at T2, and after a time related decrease, the booster dose induced a serological response in 72.7% of enrolled patients. In conclusion, the vaccine anti SARS-CoV-2 is immunogenic in patients under immunosuppression, and is not related to the development of ADRs. We also suggest that the booster dose could be used to increase the efficacy of the vaccination, particularly in women.
Abstract
Background and Aims
In end-stage kidney disease (ESKD) patients, atherosclerosis is a key-player for cardiovascular risk, being influenced by endothelial dysfunction, inflammation and ...mineral dysmetabolism. Omentin-1 is an adipokine involved in various pathological conditions (diabetes, metabolic syndrome, obesity), and has recently been studied as a prognostic factor for atherosclerosis progression and mortality in the general population. In this study, we evaluated the possible relationships between Omentin-1 and incipient carotid atherosclerosis in the clinical setting of ESKD.
Method
Circulating blood Omentin-1 levels were measured in a cohort of 77 asymptomatic ESKD patients (40 kidney transplant recipients, Ktx and 37 chronic hemodialysis patients, HD) and in 30 healthy controls. Carotid intima-media thickness (cIMT) was measured before a single HD session or before a Ktx outpatient visit. Pathological cIMT was defined for mean values > 0.9 mm and/or an unilateral cIMT above the 75th percentile.
Results
Omentin-1 levels were higher in the entire ESKD cohort than in healthy controls (324 90.3-770 vs. 110 35.4-240.9 pg/ml; p = 0.03). Ktx patients had lower levels than HD patients (p = 0.01) while higher Omentin-1 levels were found in HD patients (474.9 197.2-1432.1 ng/ml) compared to both healthy subjects (p = 0.009) and Ktx (p = 0.01). Mean cIMT in all ESKD was 0.78 ± 0.32 mm. 36 patients (46.7%) with pathological cIMT values displayed lower Omentin-1 levels as compared with others (168.7 51.1-457.8 vs 474.9 197.2-1432.1 and p = 0.004). Multivariate correlations analyses indicated Omentin-1 as the stronger independent predictor of carotid atherosclerosis (β-0.687; p = 0.03) in the whole cohort, even more than age, total cholesterol and diastolic BP.
Conclusion
In ESKD patients, Omentin-1 reflects the severity of carotid atherosclerosis independently from traditional confounders and may serve as an additive biomarker for risk prediction and risk stratification. Future studies are awaited to confirm these preliminary findings in larger cohorts.
Abstract
Background and Aims
Several evidences demonstrate that chronic dialysis treatment alters troponin levels, even in the absence of an acute myocardial event, although the underlying causes ...remain largely unclear. In this small pilot study, we aimed at analyzing high sensitivity troponin T (HsTnT) in a cohort of dialysis patients to identify the potential clinical predictors.
Method
HsTnT levels were measured together with common laboratory and clinical parameters in 39 chronic dialysis patients (middle age: 65±12 aa; 82% M; 30 in hemodialysis and 9 in peritoneal dialysis). The patients underwent also a complete echocardiography assessment.
Results
HsTnT levels were higher than normal reference values (median 46.1 ng/L IQR 33.5-84.3),but showing no differences between hemodialysis and peritoneal dialysis patients (p=0.19). At correlation analyses, HsTnT were strongly associated with beta2-MCG (R=0.43; p=0.008), Hemoglobin (r=-0.47; p=0.002) and, in particular, with some echocardiography parameters such as ejection fraction (R=-0.29; p=0.05), E/E’ratio (R=0.56; p=0.006) and LAVI (R=0.41; p=0.05) Figure 1.
Conclusion
In a small cohort of dialysis patients, high HsTnt levels were at the crossroad between the severity of functional heart dysfunction and anemia. Larger studies are advocated to further clarify the role of HsTnT as a potential biomarker reflecting the anemic cardiorenal syndrome which characterizes uremic subjects.
Abstract
Background and Aims
Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a ...lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients.
Method
Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls.
Results
Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46, p<0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p<0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p<0.001). In a multivariate model including all univariate predictors (R2=61%, p<0.001) only ALP (β=0.70,p<0.001), CRP (β=0.49,p<0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p<0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p<0.001) (Figure 1).
Conclusion
Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.
Figure:
Background
Mineral bone disease (MBD) is remarkably frequent among chronic hemodialysis (HD) patients. In this setting, deranged PTH levels portend an adjunctive risk of worsen outcomes. Various ...evidence exists demonstrating that PTH strongly induces Cathepsin-K, a cysteine protease mainly found in lysosomes of osteoclasts and macrophages which promotes bone and extracellular matrix remodelling. Cathepsin-K levels are altered in various bone disorders, systemic inflammation and even in non-advanced CKD. In this study, we tested the hypothesis of an association between Cathepsin-K, uremic-MBD and circulating PTH levels in a cohort of chronic HD patients.
Methods
We measured Cathepsin-K in 85 stable chronic HD patients and dialysis vintage > 6 months by a commercially available ELISA kit and we collected routine clinical parameters, including intact PTH. Patients were further stratified according to their “on- target” or “off-target” PTH status.
Results
Cathepsin-K levels were significantly higher in HD patients than in healthy controls (
p
< 0.0001) and were independently associated with alkaline phosphatase (β = 0.37;
p
< 0.001), PTH (β = 0.30;
p
= 0.02) and C-reactive protein (β = 0.24;
p
= 0.008) levels. Cathepsin-K was also higher in patients with off-target PTH as compared to those with controlled PTH levels (230 40–420 vs. 3250 820–4205 pg/mL;
p
< 0.0001). At ROC analyses, Cathepsin-K levels were able to identify off-target PTH and parathyroidectomized patients (AUCs 0.85 95% CI 0.71–0.98 and 0.97 95% CI 0.92–0.99, respectively).
Conclusion
In chronic HD patients, Cathepsin-K associates with PTH levels, raising the intriguing hypothesis that this protein represents a causal link between mineral and inflammatory complications and could be tested as a candidate biomarker of MBD severity and PTH balance.
The book describes the development of innovative silicon sensors known as ultra-fast silicon detectors for use in the space-time tracking of charge particles. The first comprehensive collection of ...information on the topic, otherwise currently scattered in existing literature, this book presents a comprehensive introduction to the development of ultra-fast silicon detectors with the latest technology and applications from the field. It will be an ideal reference for graduate and postgraduates studying high energy and particle physics and engineering, in addition to researchers in the area. Key features Authored by a team of subject area specialists, whose research group first invented ultra-fast silicon detectors The first book on the topic to explain the details of the design of silicon sensors for 4-dimensional tracking Presents state-of-the-art results, and prospects for further performance evolutions The Open Access version of this book, available at www.taylorfrancis.com/e/9780367646295 , has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license.
- Authored by an authority in the area, whose research group first invented ultra-fast silicon detectors - The first book on the topic to explain 4-dimensional tracking - Interdisciplinary topic, ...with applications in other area such as medicine
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