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    Mean corpuscular volume is associated with endothelial dysfunction and predicts composite cardiovascular events in patients with chronic kidney disease
    (WILEY-BLACKWELL, 2013) Solak, Yalcin; Yilmaz, Mahmut Ilker; Saglam, Mutlu; Demirbas, Seref; Verim, Samet; Unal, Hilmi Umut; Gaipov, Abduzhappar
    AimMean corpuscular volume (MCV) is a measure of size of red blood cells. Recently a few studies showed an association of macrocytosis with all-cause mortality. We aimed to assess the relationship of MCV with cardiovascular (CV) morbidity and mortality in patients with chronic kidney disease (CKD), and the effect of MCV on endothelial function. MethodsThis is an observational cohort study with a prospectively maintained cohort of patients with stage 1-5 CKD. Estimated glomerular filtration rate (eGFR), flow mediated dilatation (FMD) and laboratory values were measured at baseline. Multivariate linear and Cox regression analyses were used to predict independent associations of FMD and composite CV events, respectively. ResultsA total of 309 patients were included in the study. In contrast to anaemia MCV did not show a significant change among CKD groups. MCV was an independent predictor of FMD in addition to serum haemoglobin, CRP, diabetes, systolic blood pressure (SBP) and eGFR. Median MCV value was 85fl. Kaplan-Meier analysis showed that at 38 months the survival rate was 97.6% in the group with MCV < 85 compared to 81.6% in the arm with MCV 85 (P<0.001, log-rank test). Cox regression analysis showed MCV as a predictor of composite CV events independent of major confounding factors. ConclusionThis is the first study in the literature showing an independent association of MCV and FMD. Our results also determined MCV as an independent predictor of composite CV events independent of anaemia, inflammation, diabetes and eGFR in patients with CKD.
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    Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease
    (SPRINGER, 2013) Solak, Yalcin; Yilmaz, Mahmut Ilker; Sonmez, Alper; Saglam, Mutlu; Cakir, Erdinc; Unal, Hilmi Umut; Gok, Mahmut
    Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients. 225 subjects with stage 3-5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction. There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR a parts per thousand yen3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity. NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.
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    Renal Anemia of Inflammation: The Name Is Self-Explanatory
    (KARGER, 2011) Yilmaz, Mahmut Ilker; Solak, Yalcin; Covic, Adrian; Goldsmith, David; Kanbay, Mehmet
    Background: Anemia is inevitable as chronic kidney disease (CKD) advances. With the advent of erythropoietin-stimulating agents (ESAs), considerable improvement has been achieved in the management of anemia. However, some patients show a reduced response to ESAs. Methods: Many factors affect the response to ESA treatment. CKD is now considered as an inflammatory disorder and this understanding led to the recognition of the central role of inflammation in ESA resistance. Inflammation is related to untoward outcomes, including atherosclerosis and anemia, in the CKD population. Furthermore, recognition of deleterious effects of proinflammatory markers at different levels of erythropoiesis led to a change in the name of 'anemia of chronic disease' to anemia of inflammation. Results: The discovery of hepcidin as the major controller of iron metabolism in anemia of inflammation answered many questions regarding the interaction of erythropoietin, iron and bone marrow. Hepcidin production in the liver is driven by three major factors: inflammation, iron overload and anemia/hypoxia. Hepcidin levels are increased in patients with CKD due to the interaction of many factors; a comprehensive understanding of these pathways is thus critical in the effort to alleviate anemia of inflammation and ESA resistance. Conclusion: In this review, we discussed the epidemiology, determinants and consequences of anemia of inflammation in CKD patients with special emphasis on the central role of hepcidin along with molecular pathways driving its production. Copyright (C) 2011 S. Karger AG, Basel
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    Serum neutrophil gelatinase-associated lipocalin is associated with cardiovascular events in patients with chronic kidney disease
    (SPRINGER, 2015) Solak, Yalcin; Yilmaz, Mahmut Ilker; Siriopol, Dimitrie; Saglam, Mutlu; Unal, Hilmi Umut; Yaman, Halil; Gok, Mahmut
    Background Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family best known as a novel and early marker of acute kidney injury (AKI). Recent data suggest that NGQueryAL is not only a marker of AKI, but also an important player in the vascular remodeling, atherosclerotic plaque stability and thrombus formation. We conducted this study to investigate the association of serum NGAL levels with fatal and composite (fatal and non-fatal) cardiovascular events (CVE) in a cohort of patients with stage 1-5 CKD. Methods This was an observational cohort study in which serum NGAL was obtained from 298 CKD (stages 1-5) patients. Fatal and composite CVE were recorded for a median 41 months. We examined alteration of serum NGAL through CKD groups as well as association with inflammatory markers. We also performed a Cox regression analysis to determine the association of NGAL with predefined clinical outcomes. Results The median value of NGAL was 50.5 ng/mL (IR 47.6-54.9 ng/mL), and higher NGAL values were recorded in diabetic patients. In a multiple linear regression model, including all univariate associates of NGAL, only log eGFR, log hs-CRP and log HDL cholesterol maintained an independent association with log NGAL. During the observational period, 30 patients died due to cardiovascular causes and 69 non-fatal CVE were registered. In the fully adjusted model, we observed a 2.08-fold increase in the risk of fatal CVE and a 1.50-fold increase in the risk of fatal and non-fatal CVE for each increment of 1 SD in log NGAL values. Conclusions This is the first study that shows that serum NGAL is associated with cardiovascular events (fatal and non-fatal) in patients with CKD, independently of traditional risk factors, renal function and inflammation.