Yasemin Erten

Neutrophil to Lymphocyte Ratio in Evaluation of Inflammation in Patients with Chronic Kidney Disease

Aim: The current data have proven the pivotal role of inflammation in the development of atherosclerosis and cardiovascular diseases in patients with chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has increasingly been reported as a measure of systemic inflammation. This study assessed N/L ratio and investigated its associations with standard inflammatory biomarkers in different stages of CKD patients. Material and methods: This cross-sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis patients, and 30 healthy subjects. N/L ratio and important clinical and laboratory parameters were registered. Multivariate regression analyses were carried out to investigate the relations of N/L ratio. Results: N/L ratio was significantly higher in each patient group compared to the healthy subjects (for all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r = 0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p = 0.002) levels and negatively correlated with hemoglobin (r = −0.271, p = 0.001), serum albumin (r = −0.400, p < 0.001), and high-density lipoprotein (HDL) cholesterol levels (r = −0.302, p < 0.001). In CKD patients with hypertension (HT), higher N/L ratio was detected when compared to those without HT (p = 0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and hs-CRP levels were found to be independent predictors of the ratio after adjusting for significant covariates (p < 0.001). Conclusion: An easy and inexpensive laboratory measure of N/L ratio might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients

Background:  Sleep complaints are common in end‐stage renal disease. We aimed to investigate the relationship between sleep‐related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels.

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.

Predictive markers of asymptomatic atherosclerosis in end-stage renal disease patients

Objective: Uremia is associated with accelerated atherosclerosis and increased cardiovascular mortality in patients with end-stage renal disease (ESRD). Cardiac injury markers, such as myoglobin, creatine kinase-MB (CK-MB), or troponins, frequently used to recognize acute coronary events, may be falsely elevated in this patient group. In this study, our aim was to (i) test serum levels of myoglobin, CK-MB, and troponin I (cTnI) in ESRD patients without coronary artery disease (CAD) and compare the results with healthy controls and (ii) to investigate the association between these markers and carotid artery intima–media thickness (CA–IMT), high-sensitive C-reactive protein (hs-CRP), and serum uric acid (SUA) levels in ESRD patients. Materials and methods: Fifty-two ESRD patients (25 hemodialysis and 27 peritoneal dialysis) and 17 healthy controls were included in the study. Serum levels of myoglobin, CK-MB, and cTnI were measured and ultrasonographic CA–IMT was determined in all participants. SUA and hs-CRP levels were only measured in the ESRD group. Results: Serum myoglobin, CK-MB levels, and the mean CA–IMT were significantly higher in ESRD group (p < 0.01), whereas cTnI levels were not different compared to healthy controls (p = 0.70). There was also a positive correlation between CA–IMT and cTnI levels (p = 0.003, r = 0.35) and CA–IMT and hs-CRP (p = 0.03, r = 0.30) or SUA levels (p = 0.003, r = 0.43). Conclusion: cTnI may serve as a more sensitive marker in detecting cardiovascular events in patients with renal failure. Besides the traditional risk factors of atherosclerosis, cTnI, hs-CRP, and SUA may have a predictive role in recognizing premature atherosclerosis in ESRD patients.

The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-α, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-α levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 ± 387.86 ng/mL) than hemodialysis (97.68 ± 244.96 ng/mL,) and control (41.33 ± 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-α (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = −0.305, p = 0.01), (r = −0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (β = 0.369, p = 0.001) and IL-6 (β = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-α. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.

Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: Identification of new case with novel mutation

BACKGROUND Chronic renal failure (CRF) is a serious complication of Fabry disease (FD). The aims of the present study were to determine the prevalence of unrecognized FD in Turkish hemodialysis population and to investigate the molecular background. METHOD Primarily, α-galactosidase A (α-Gal A) activity was investigated on DBS in 1136 patients of both sexes who underwent dialysis for CRF in Turkey. The disease was confirmed by analyzing enzyme activity in leukocyte and GLA gene sequencing in all patients in whom α-Gal A level was 40% of normal or less. RESULTS Mean age of the patients (44.5% female, 52.5% male) was 56.46±15.85 years. Enzyme activity was found low with DBS method in 12 patients (four males, eight females). Two men, but no women, were diagnosed with FD by enzymatic and molecular analysis. In consequence of genetic analysis of a case, a new mutation [hemizygote c.638C>T (p.P214S) missense mutation in exon 5] was identified, which was not described in literature. Family screening of cases identified six additional cases. CONCLUSION As a result of this initial screening study performed on hemodialysis patients for the first time with DBS method in Turkey, the prevalence of FD was detected as 0.17%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.

Left Ventricular Hypertrophy and Blood Pressure Control in Automated and Continuous Ambulatory Peritoneal Dialysis Patients

Hypertension, non‐dipper blood pressure (BP) pattern and decrease in daily urine output have been associated with left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients. However, there is lack of data regarding the impact of different PD regimens on these factors. We aimed to investigate the impact of circadian rhythm of BP on LVH in end‐stage renal disease patients using automated peritoneal dialysis (APD) or continuous ambulatory peritoneal dialysis (CAPD) modalities. Twenty APD (7 men, 13 women) and 28 CAPD (16 men, 12 women) patients were included into the study. 24‐h ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography besides routine blood examinations were performed. Two groups were compared with each other for ABPM measurements, BP loads, dipping patterns, left ventricular mass index (LVMI) and daily urine output. Mean systolic and diastolic BP measurements, BP loads, LVMI, residual renal function (RRF) and percentage of non‐dippers were found to be similar for the two groups. There were positive correlations of LVMI with BP measurements and BP loads. LVMI was found to be significantly higher in diastolic non‐dippers compared to dippers (140.4 ± 35.3 vs 114.5 ± 29.7, respectively, P = 0.02). RRF and BP were found to be independent predictors of LVMI. Non‐dipping BP pattern was a frequent finding among all PD patients without an inter‐group difference. Additionally, higher BP measurements, decrease in daily urine output and non‐dipper diastolic BP pattern were associated with LVMI. In order to avoid LVH, besides correction of anemia and volume control, circadian BP variability and diastolic dipping should also be taken into consideration in PD patients.

Association of the Angiotensinogen M235T and APO E Gene Polymorphisms in Turkish Type 2 Diabetic Patients with and without Nephropathy

Background: Diabetic nephropathy (DN) is a leading cause of diabetes-related morbidity and mortality. The aim of this study was to evaluate the relationship of AGT M235T and apoprotein E (APO E) gene polymorphism with DN in Turkish patients of Type 2 diabetes, and to compare genotype and allele distributions among DN patients, non-DN patients, and healthy controls. Methods: AGT M235T and APO E genotype and allele analysis were performed in 111 DN patients, 108 non-DN patients, 106 healthy control subjects for APO E genotype, and 100 for AGT M235T genotype polymorphism. APO E and AGT M235T genotype were determined by RFLP-PCR. Results: The frequencies of APO E ε2/3, ε 3/3, ε 3/4 genotypes were 22.7%, 60%, 60%, respectively, among DN patients and 6.6%, 80%, 10.4%, respectively (p < 0.001), in the non-DN patients. The frequencies of AGT M235T MM, MT, TT genotypes among the same groups were 17%, 46%, 37% and 21%, 63%, 16%, respectively (p < 0.02). Having the ε2/3 genotype and TT genotype increased the risk for DN nephropathy [4.8-fold (95% CI: 1.94–11.67), 2.9-fold (95% CI: 1.27–6.69), respectively]. Conclusion: Our study has shown that AGT M235T TT genotype and APO E ε 2/3 genotype may be linked to a risk for DN among Turkish population.

Effects of Everolimus on Cytokines, Oxidative Stress, and Renal Histology in Ischemia-Reperfusion Injury of the Kidney

Background. To evaluate the effects of everolimus on renal ischemia-reperfusion injury (IRI). Methods. Wistar albino rats were divided into control, ischemia-reperfusion (IR), and ischemia-reperfusion/everolimus (IR/eve) groups. Everolimus was administered for seven consecutive days to the IR/eve group prior to injury. IR and IR/eve groups underwent forty-five minutes ischemia followed by the application of reperfusion at 2 and 24 hours. Blood samples and kidneys were taken from all animals. Results. Serum blood urea nitrogen and creatinine levels increased at two hours of reperfusion in the IR and IR/eve groups, and decreased at 24 hours of reperfusion in the IR group. In the IR/eve group, we detected significantly high interleukin-6 levels and low tumor necrosis factor-α and malondialdehyde levels at 24 hours. Myeloperoxidase levels increased at two hours of reperfusion in the IR/eve group, but decreased significantly at 24 hours. Everolimus did not improve renal tubular and interstitial injuries in renal IRI. Conclusions. It has been demonstrated that pretreatment with everolimus has beneficial effects on cytokines and oxidative stress in renal IRI. However, these effects are insufficient for the correction of histopathological changes and restoration of normal kidney function.

The Relationship among Asymmetric Dimethylarginine (ADMA) Levels, Residual Renal Function, and Left Ventricular Hypertrophy in Continuous Ambulatory Peritoneal Dialysis Patients

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial-based nitric oxide synthase. Its level is increased by end stage renal disease. However, most studies showing an increase in ADMA in dialysis patients have focused on hemodialysis. Results with peritoneal dialysis patients have been more inconclusive. Recent studies suggest that ADMA may be a new cardiovascular risk factor. The aim of the present study was to evaluate the relationship between ADMA levels, residual renal function, and left ventricular hypertrophy in peritoneal dialysis patients. Serum ADMA measurements and echocardiographic evaluations were performed in 54 peritoneal dialysis patients and 26 healthy volunteers. Residual renal function was measured in peritoneal dialysis patients by urea clearance from a urine collection. Thirty-two of the 54 peritoneal dialysis patients had residual renal function. ADMA levels of the peritoneal dialysis group were found to be significantly higher than those of healthy individuals (p = 0.03). Within the peritoneal dialysis group, ADMA levels of patients with residual renal function were significantly lower than those without residual renal function (p = 0.01), though they were still higher than the ADMA levels of the control group (p = 0.04). Serum levels of ADMA were positively correlated with left ventricular mass index (r = 0.29, p = 0.01) and negatively correlated with early mitral inflow velocity (Em) (r = −0.28, p = 0.01), Em/Late mitral inflow velocity (Am) (r = −0,32, p = 0.00), and isovolumetric relaxation time (r = −0.30, p = 0.01). In conclusion, increased ADMA levels seem to be associated with left ventricular hypertrophy in peritoneal dialysis patients, and residual renal function may lead to a reduction of serum ADMA levels.