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    Association of ambulatory arterial stiffness index with sEPCR in newly diagnosed hypertensive patients
    (Taylor & Francis Ltd, 2015) Yilmaz, Hakki; Cakmak, Muzaffer; Inan, Osman; Darcin, Tahir; Aktas, Aynur; Gurel, Ozgul Malcok; Bilgic, Mukadder Ayse
    Aim: Increased arterial stiffness is strongly associated with cardiovascular diseases, while thrombotic events are more common than hemorrhagic events in hypertensive patients. Markers of a hypercoagulable state may also predict future cardiovascular events in hypertensive patients. Here, we speculated that increased arterial stiffness might lead to the development of a hypercoagulable state that can play a role in the thrombotic complications of hypertension. Soluble endothelial protein C receptor (sEPCR) is one such marker of hypercoagulation. The ambulatory arterial stiffness index (AASI) could be accepted as a non-invasive measure of arterial stiffness. The aim of this study was to investigate association of AASI with levels of sEPCR in newly diagnosed hypertensive patients. Materials and methods: The study included 263 newly diagnosed essential hypertensive patients and 55 healthy normotensive controls. All subjects underwent 24 h ambulatory blood pressure monitoring (ABPM); the AASI was derived from ABPM tracings. Plasma sEPCR was measured by ELISA. Results: Hypertensive patients (n=263) had higher AASI, C-reactive protein (CRP) and sEPCR versus the normotensive healthy group (n=55). Univariate analysis showed that AASI was positively associated with age (r=0.212, p< 0.001) body mass index (r=0.412, p<0.001), pulse pressure (r=0.350, p<0.001), plasma sEPCR (r=0.894, p<0.001), 24-h heart rate (r=0.176, p=0.001) and inversely related to high-density lipoprotein (HDL) (r=-0.293, p<0.001). Multivariate analyses revealed that sEPCR and HDL are independently correlated to AASI. Conclusion: We suggest that increased AASI is associated with elevated sEPCR. It might be responsible for subsequent thrombotic events in newly diagnosed hypertensive patients.
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    Can neutrophil-lymphocyte ratio be independent risk factor for predicting acute kidney injury in patients with severe sepsis?
    (Informa Healthcare, 2015) Yilmaz, Hakki; Cakmak, Muzaffer; Inan, Osman; Darcin, Tahir; Akcay, Ali
    Aim: Neutrophil-lymphocyte ratio (NLR) is an easily calculated, sensitive, and accurate marker for prognosis and diagnosing sepsis, cardiovascular disease and cancer. As sepsis and septic shock are main causes of acute kidney injury (AKI) intensive care unit (ICU), we investigated whether NLR is an early predictor of AKI in patients with severe sepsis. We compared NLR's predictive power with that of other inflammation-related variables. Methods: Between December 2011 and November 2013, we enrolled 118 consecutive cases with severe sepsis admitted to ICU in this retrospective study. Levels of C-reactive protein (CRP), NLR, and white blood cell count (WBC) were recorded on admission and patients' renal function was monitored for seven consecutive days. Results: The rate of AKI occurrence 7 days after enrollment was 57.6%. NLR levels were higher in the AKI group (Group 1) than in the non-AKI group (Group 2) on the day of ICU admission (p<0.001). AKI development was independently associated with NLR, Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of invasive mechanical ventilation (MV) in multivariate logistic regression analysis. The area under the receiver-operating characteristic (ROC) curve of NLR for predicting AKI was 0.986, which was superior to WBC and CRP (p<0.05). The cut-off value of 10.15 for NLR had the highest validity for predicting AKI in patients with severe sepsis. The sensitivity, specificity, negative-predictive value (NPV), and positive-predictive value (PPV), for this cut-off value was 90.2%, 92.9%, 90.4%, and 92.7%, respectively. Conclusion: NLR is superior to CRP, and WBC for predicting the development of AKI in patients with severe sepsis.
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    Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?
    (Springer India, 2016) Yilmaz, Hakki; Cakmak, Muzaffer; Darcin, Tahir; Inan, Osman; Bilgic, Mukadder Ayse; Bavbek, Nuket; Akcay, Ali
    Functional iron deficiency (FID) incidence is gradually increasing in hemodialysis (HD) patients. Recently, high levels of GDF-15 supressed the iron regulatory protein hepcidin and GDF-15 expression increased in iron-deficient patients. The relationship between FID, GDF-15, and hepcidin is currently unknown. The present study aimed to evaluate the association between GDF-15, hepcidin, and FID in chronic HD patients. Serum GDF-15 and hepcidin concentrations were measured in 105 HD patients and 40 controls. FID is defined as serum ferritin > 800 ng/mL, TSAT < 25 %, Hb levels < 11 g/dL, and reticulocyte haemoglobin content (CHr) < 29 pg. Serum GDF-15 and hepcidin levels were increased significantly in HD patients with FID, compared to HD patients without anemia and controls. GDF-15 correlated with ferritin, hepcidin, and CRP in the entire cohort. GDF-15 was related to ferritin and CRP in HD patients with FID. GDF-15 is better diagnostic marker than hepcidin for detection of FID [AUC = 0.982 (0.013) versus AUC = 0.921 (0.027); P = 0.0324]. GDF-15 appears to be a promising tool for detection of FID. High levels of ferritin and CRP correlated with GDF-15. Our results support GDF-15 as a new mediator of FID via hepcidin, chronic inflammation, or unknown pathways.
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    Circulating irisin levels reflect visceral adiposity in non-diabetic patients undergoing hemodialysis
    (Taylor & Francis Ltd, 2016) Yilmaz, Hakki; Cakmak, Muzaffer; Darcin, Tahir; Inan, Osman; Sahiner, Enes; Demir, Canan; Aktas, Aynur
    Background: Recent evidence suggests that increased visceral adiposity is a strong independent risk factor for cardiovascular death and all-cause mortality in hemodialysis (HD) patients. Irisin, which is a novel myokine, can play critical roles in diabetes and adiposity. The purpose of our study was to investigate whether serum irisin levels are associated with body mass index, waist circumference (WC), and total fat mass in non-diabetic patients undergoing maintenance HD.Methods: This cross-sectional study included 108 non-diabetic HD patients and 40 age- and sex-matched apparently healthy subjects. Serum irisin concentrations were determined using an enzyme-linked immunosorbent assay. Body fat composition (TBF-410 Tanita Body Composition Analyzer) was measured and calculated.Results: Serum irisin levels did not differ between HD patients and the healthy controls (523.50 +/- 229.32 vs. 511.28 +/- 259.74, p=0.782). Serum irisin levels were associated with age (r=0.314; p=0.006), HOMA-IR (r=0.472; p=0.003), WC (r=0.862; p<0.001), and total fat mass (r=0.614; p<0.001). In multivariate regression analysis, WC (=1.240, p<0.001) and total fat mass (=0.792, p=0.015) were the variables that were significantly associated with irisin concentrations (R-2=0.684, p<0.001) after adjusting for confounding factors (age and HOMA-IR). Conclusions: These results suggest that serum irisin levels are related to visceral adiposity in non-diabetic HD patients.
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    Serum galectin-3 levels were associated with proteinuria in patients with Familial Mediterranean Fever
    (Springer, 2015) Yilmaz, Hakki; Inan, Osman; Darcin, Tahir; Bilgic, Mukadder Ayse; Akcay, Ali
    The most common and pernicious complication of Familial Mediterranean fever (FMF) is renal amyloidosis, usually affecting the kidneys, leading to end-stage renal failure. FMF-related renal amyloidosis needed to be diagnosed early. Optimal colchicine dose is effective in preventing and reversing renal amyloidosis. Galectin-3, profibrotic mediator, has regulatory functions in inflammation, fibrosis and tumorigenesis. Galectin-3 is a strong prognostic marker for heart failure. Galectin-3 plays role in diabetic nephropathy and chronic kidney disease. The aim of the study is to investigate whether galectin-3 is related to proteinuria and amyloidosis in FMF. Seventy-five FMF patients who have no exclusion criteria and healthy controls (n = 36) were included. Serum galectin-3 was measured and morning spot urine was collected for determination of the protein/creatinine ratio (PCR). Serum Galectin-3 levels were significantly higher in FMF patients than the control group [969.66 (3825) pg/mL vs. 238 (921) pg/mL, respectively; P < 0.001]. We classified into two groups: Group1 (n = 48) had FMF patients with proteniuria, Group2 (n = 27) had FMF patients without proteinuria. Group1 had higher levels of galectin-3 than Group2 [1106(3812) pg/mL vs. 867.3(1433) pg/mL, P < 0.001]. Galectin-3 levels were correlated with PCR in whole group and FMF group (r = 0.785, P < 0.001 and r = 0.803, P < 0.001). In ROC curve, best cutoff value = 581.50 pg/mL was used to detect proteinuria (sensitivity = 91.7 %, specificity = 71.4 %, AUC = 0.879) and optimal cutoff value = 1458.00 pg/mL was an indicator of nephrotic-range proteinuric (sensitivity = 100 %, specificity = 92.1 %, AUC = 0.983). Galectin-3 is associated with proteinuria and renal amyloidosis in FMF. Galectin-3 may play role in pathogenesis of amyloidosis.
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    Serum levels of endocan correlate with the presence and severity of pre-eclampsia
    (Taylor & Francis Inc, 2016) Cakmak, Muzaffer; Yilmaz, Hakki; Baglar, Esra; Darcin, Tahir; Inan, Osman; Aktas, Aynur; Celik, Huseyin Tugrul
    Background: Endocan, a cysteine-rich dermatan sulfate proteoglycan expressed by endothelial cells, is seemed to be a new biomarker for endothelial dysfunction. Pre-eclampsia (PE) is characterized by the new onset of hypertension, proteinuria after 20 weeks of gestation, placental vascular remodeling, systemic vascular inflammation and endothelial dysfunction. The aim of this study was to investigate the relationship of PE and its severity with serum endocan levels. Methods: A cross-sectional study was performed. Serum was collected from women with PE and normotensive controls. Serum endocan and tumor necrosis factor alpha (TNF-alpha) concentrations were measured by a specific enzyme linked immunosorbent assay. Results: Patients with PE had significantly higher median (interquartile range) endocan and mean TNF-alpha concentrations than controls [20.04 (12.26) ng/mL vs 15.55 (6.19) ng/mL, p < 0.001 for endocan; 26.49 +/- 12.14 pg/mL vs 14.62 +/- 5.61 pg/mL, p < 0.001 for TNF-alpha; respectively]. Serum endocan concentrations were positively correlated with systolic blood pressure (r = 0.618, p < 0.001), diastolic blood pressure (r = 0.608, p < 0.001), the amount of 24-h proteinuria (r = 0.786, p < 0.001) and TNF-alpha (r = 0.474, p < 0.001) in women with PE. In subgroup analysis, patients with severe PE had significantly higher endocan concentrations than those with mild PE. Receiver operating characteristic analysis of endocan was used to identify the patients with PE and also discriminating between mild and severe PE. Conclusion: Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seem to be associated with the severity of the disease.