Pentraxin 3 as a new indicator of cardiovascular-related death in patients with advanced chronic kidney disease

Pentraxin 3 (PTX3) is involved in inflammatory response by recognizing pathogens and damaged tissues. The aim of this study was to assess the relationship between PTX3 levels and all‑cause and cardiovascular (CV) mortality in patients with chronic kidney disease (CKD) during 5‑year follow‑up. The study included 78 patients (51 on hemodialysis and 27 on predialysis). We measured the levels of PTX3, calcium, phosphate, intact parathyroid hormone, high-sensitivity Creactive protein (hs-CRP), interleukin 6 (IL‑6), fibroblast growth factor 23 (FGF‑23), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), fetuin A, tumor necrosis factor receptor 2 (TNFR2), transforming growth factor $\beta1$ ($TGF‑\beta 1$), hepatocyte growth factor (HGF), stromal cell‑derived factor $1\alpha$ ($SDF‑1\alpha$), and thrombomodulin (TM). In a subgroup of 45 patients, fragments of the radial artery obtained during creation of hemodialysis access were stained for calcifications. In 51 patients, ultrasonography was performed to assess common carotid artery intima–media thickness (CCA‑IMT). The median serum concentrations of PTX3 were 1.43 ng/ml (interquartile range, 0.74–2.50). Higher concentrations of fibrinogen, hs‑CRP, IL‑6, TNFR2, $TGF‑\beta$ 1, HGF, OPN, OPG, FGF‑23, TM, and $SDF‑1\alpha$ and lower albumin and uric acid levels were observed in patients with PTX3 above the median. During follow‑up, 27 patients (35%) died, including 25 due to CV causes. In contrast to hs-CRP levels, baseline PTX3 levels predicted CV mortality independently of classic CV risk factors. PTX3 levels also significantly predicted mortality after adjustment for age, baseline dialysis status, serum OPG and CRP levels, radial artery calcifications, and CCA‑IMT. We postulate that PTX3 might be an early marker of CV mortality in patients with advanced CKD, yet before the increase in the levels of a specific marker for systemic inflammation such as hs‑CRP

Ultrafiltration rate and diabetes as useful indicators of cardiovascular-related death in hemodialysis patients below 60 years of age

Background: The survival rate of elderly hemodialyzed (HD) patients is commonly thought to be poor. In a prospective, single center, non-interventional, observational study, the cause of all-cause and cardiovascular (CV) and heart failure (HF) mortality in this patient group were examined and compared with a younger cohort (below 60 years). Material/Methods: The study included 223 patients (90 women and 133 men) with age ranging from 34.5 to 75.0 years treated with HD. Median duration of HD was 70.0 months (24.0-120.0). Mortality data was collected over a period of six years. We divided patients into groups: <60 (n=123), ≥60 years (n=100), and with (n=33) and without DM type 2 (n=190). Results: During a six-year follow-up, 100 patients (44.8%) died, including 83 (37.2%) patients who died due to CV reasons. Median follow-up was 2015.0 days (946.0-2463.0) with the median time to death of 1166.0 days (654.5-1631.0). The factors negatively affecting patients’ survival in univariate Cox regression analysis included for all-cause mortality were: inter-dialytic weight gain (IDWG) (hazard ratio [HR]=1.60; p=0.01), ultrafiltration (UF) rate (HR=3.63; p=0.012) for group <60 years; for CV death: UF rate (HR=4.20; p=0.03), DM (HR=5.11; p=0.002) for group <60 years; for HF death: mellitus type 2 (DM) (HR=2.93; p=0.027) for group ≥60 years). In a multivariate Cox regression analysis for patients <60 years, the UF rate was the only independent predictor of all-cause mortality (HR 3.63 (1.34-9.67); p=0.011). Both DM (HR 4.91 (1.71-14.10); p=0.003) and UF rate (HR 3.62 (1.04-12.61); p=0.044) were independent predictors of CV-related mortality in patients <60 years. Conclusions: The UF rate can be a simple, useful indicator of higher long-term all-cause and CV mortality in HD patients <60 years of age. Also, DM may be a predictor of CV–related mortality in younger HD patients

Asymmetric dimethylarginine as a useful risk marker of radial artery calcification in patients with advanced kidney disease

Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor $1\alpha$ ($SDF1\alpha$), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and $SDF1\alpha$ levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between $SDF1\alpha$ and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. Circulating ADMA levels indicate medial arterial calcification in patients with CKD

Neutrophil-to-lymphocyte ratio predicts long-term all-cause mortality in patients with chronic kidney disease stage 5

Introduction: A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a strong biomarker of infl ammation. Aim: We sought to evaluate the impact of NLR on long-term all-cause and cardio-vascular (CV) mortality in hemodialysis (HD) patients. Material and Methods: A total of 84 chronic kidney disease (CKD) stage 5 patients with 54 of them on HD, with a median age of 61.5 (51.3-74.8) years were enrolled. The association between NLR and clinical biomarkers was investigated. Multivariable Cox regression analysis was used to find significant predictors of all-cause and CV mortality at follow-up. Results: The median NLR (interquartile range) was 3.0 (2.1-4.1). Patients with NLR ≥3.9 (the highest tertile) had higher fi ve-year all-cause mortality then remaining patients (53.6% vs. 30.4%; p = 0.039). On the contrary, only a trend towards increased CV mortality was observed (25.0% vs. 42.9%; p = 0.10). NLR ≥3.9 was a significant predictor of all-cause mortality at five years [hazard ratio (95%CI): 2.23 (1.10- 4.50); p = 0.025] in Cox regression model adjusted for age, gender, and diabetes status. Similarly, while using NLR as continuous variable a significant association between NLR and all-cause mortality was confirmed even after adjustment for covariates [hazard ratio per 1 unit increase (95%CI): 1.26 (1.06–1.51); p = 0.009] with the area under the receiver operating characteristic (ROC) curve of 0.64. Correlations between NLR and WBC, concentration of fi brinogen, albumin were observed. Conclusions: Asymptomatic inflammation measured by NLR showed an association with long-term all-cause mortality in stage 5 CKD patients, even while white blood cell count was in the normal range

Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation and vascular disease in the spectrum of advanced chronic kidney disease

Background: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. Aims: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. Methods: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima‑media thickness and atherosclerotic plaques were assessed by ultrasonography. Results: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima‑media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C‑reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). Conclusions: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study