Kultigin Turkmen

The Relationship Between Neutrophil-to-Lymphocyte Ratio and Inflammation in End-Stage Renal Disease Patients

Abstract Background: Patients with end-stage renal disease (ESRD) have elevated serum levels of inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. Systemic inflammation was found to be correlated with coronary artery disease (CAD) in this population. Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and non-cardiac disorders. Data regarding NLR and its association with inflammation are lacking. We aimed to determine the relationship between NLR and inflammation in ESRD patients. Material and methods: This was a cross-sectional study involving 61 ESRD patients (25 females and 36 males; mean age: 48.3 ± 14.5 years) receiving peritoneal dialysis (PD) or hemodialysis (HD) for ≥6 months in the Dialysis Unit of Selcuk University. NLR, CRP, TNF-α, and IL-6 levels were measured. Results: NLR, serum CRP, IL-6, and TNF-α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with NLR ≥ 3.5 had significantly higher TNF-α levels when compared with patients with NLR < 3.5. In the bivariate correlation analysis, NLR was positively correlated with TNF-α in this population. Conclusions: Simple calculation of NLR can predict inflammation in ESRD patients.

Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients.

Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end‐stage renal disease (ESRD) patients. Recently, platelet‐to‐lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross‐sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C‐reactive protein, TNF‐α, IL‐6 levels were measured. PLR, NLR, serum high sensitive C‐reactive protein, IL‐6, and TNF‐α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL‐6, and TNF‐α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL‐6, and TNF‐α in this population. When we compared the association of PLR and NLR with IL‐6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF‐α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.

IL-33 Exacerbates Acute Kidney Injury

Inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33 is a proinflammatory cytokine, but its role in AKI is unknown. Here we observed increased protein expression of full-length IL-33 in the kidney following induction of AKI with cisplatin. To determine whether IL-33 promotes injury, we administered soluble ST2 (sST2), a fusion protein that neutralizes IL-33 activity by acting as a decoy receptor. Compared with cisplatin-induced AKI in untreated mice, mice treated with sST2 had fewer CD4 T cells infiltrate the kidney, lower serum creatinine, and reduced acute tubular necrosis (ATN) and apoptosis. In contrast, administration of recombinant IL-33 (rIL-33) exacerbated cisplatin-induced AKI, measured by an increase in CD4 T cell infiltration, serum creatinine, ATN, and apoptosis; this did not occur in CD4-deficient mice, suggesting that CD4 T cells mediate the injurious effect of IL-33. Wildtype mice that received cisplatin and rIL-33 also had higher levels of the proinflammatory chemokine CXCL1, which CD T cells produce, in the kidney compared with CD4-deficient mice. Mice deficient in the CXCL1 receptor also had lower serum creatinine, ATN, and apoptosis than wildtype mice following cisplatin-induced AKI. Taken together, IL-33 promotes AKI through CD4 T cell-mediated production of CXCL1. These data suggest that inhibiting IL-33 or CXCL1 may have therapeutic potential in AKI.

The Relationship between Oxidative Stress, Inflammation, and Atherosclerosis in Renal Transplant and End-Stage Renal Disease Patients

Objectives: Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and is also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima–media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in the end-stage renal disease (ESRD) patients. Ischemia-modified albumin (IMA), pentraxin-3 (PTX-3), and neutrophil-to-lymphocyte ratio (NLR) were introduced as oxidative stress and inflammatory biomarkers in ESRD. The role of Rtx in terms of atherogenesis, oxidative stress, and inflammation is still unclear. We aimed to investigate the relationship between IMA, PTX-3, NLR, and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects and ESRD patients receiving hemodialysis (HD) and peritoneal dialysis (PD). Design and methods: Cross-sectional analysis in which CIMT measurements, NLR, and serum PTX-3 and IMA levels were assessed in 18 Rtx patients (10 females; mean age: 40.0 ± 13.3 years), 16 PD patients (7 females; 40.2 ± 12.9 years), 14 HD patients (8 females; 46.6 ± 10.7 years), and 19 healthy subjects (9 females; 36.9 ± 8.9 years). Results: IMA, PTX-3, and high-sensitive C-reactive protein (hs-CRP) levels, NLR, and CIMT of Rtx patients were found to be significantly higher compared with healthy subjects ( p = 0.04, p < 0.0001, p < 0.005, p = 0.005, and p = 0.005, respectively). IMA level was positively correlated with hs-CRP and PTX-3 levels, NLR, and CIMT when all participants were included (r = 0.338, p = 0.005; r = 0.485, p < 0.0001; r = 0.304, p = 0.013; and r = 0.499, p < 0.0001, respectively). Conclusion: There has been ongoing inflammation, oxidative stress, and atherosclerosis in Rtx patients.

The Relationship between Epicardial Adipose Tissue and Malnutrition, Inflammation, Atherosclerosis/Calcification Syndrome in ESRD Patients

BACKGROUND AND OBJECTIVES Malnutrition, inflammation, atherosclerosis/calcification (MIAC) and endothelial dysfunction are the most commonly encountered risk factors in the pathogenesis of cardiovascular disease in ESRD patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between CAD and EAT was shown in patients with high risk of coronary artery disease. In this study, we aimed to investigate the relationship between EAT and MIAC syndrome in ESRD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Eighty ESRD patients and 27 healthy subjects enrolled in this cross-sectional study. EAT and coronary artery calcification score were measured by a multidetector computed tomography (MDCT) scanner. Patients with serum albumin <3.5 mg/dl were defined as patients with malnutrition; those with serum C-reactive protein level >10 ng/dl (normal range, 0-5 ng/dl) had inflammation; and those with CACS >10 had atheroscleosis/calcification. RESULTS Total CACS and EAT measurements were significantly higher in ESRD patients when compared with healthy subjects. There was a statistically significant relationship between EAT and CACS in ESRD patients (r = 0.48). EAT measurements were higher in PD patients than HD patients. Twenty-four of the patients had no component, 31 had one component, 17 had two components, and nine had all of the MIAC components. EAT was found to be significantly increased when the presence of MIAC components increased. EAT was positively correlated with age, body mass index, and presence of MIAC. These parameters were also found as independent predictors of increased EAT. CONCLUSIONS We found a relationship between EAT and components of MIAC syndrome in ESRD patients.

Health‐related qualıty of lıfe, sleep qualıty, and depressıon in peritoneal dialysis and hemodıalysıs patıents

Health‐related quality of life (HRQoL) and sleep quality (SQ) were impaired in patients with end‐stage renal disease (ESRD). The impairment of both HRQoL and SQ and being in a depressive mood were found to be associated with increased morbidity and mortality in dialysis patients. We aimed to investigate the association between SQ, HRQoL, and depression, and to define independent predictors of SQ and depression in peritoneal dialysis (PD) and hemodialysis (HD) patients. Ninety HD patients (41 females, 49 males with mean age 50 ± 15.7 years) and 64 PD patients (27 females, 37 males with mean age 52.4 ± 15.3 years) receiving renal replacement therapy for at least 3 months were screened for the assessment of SQ, HRQoL, and depression in this cross‐sectional study. A modified postsleep inventory, Short Form of Medical Outcomes Study (SF‐36) and Beck depression inventory (BDI) were applied to all patients for evaluating SQ, HRQoL, and depression, respectively. HD and PD patients had similar total SQ scores. Physical and mental component scale of HRQoL were found to be significantly higher in HD patients (p < 0.001). PD patients were found to be much more in depressive mood when compared with HD patients (p < 0.001). Independent predictors of depression in patients were mental component scale of HRQoL, gender (being female), and dialysis modality (being PD patient). Physical component scale was also found to be an independent predictor of SQ. This study showed that despite similar SQ scores between two groups, HD patients had better HRQoL and less depression than PD patients.

Sleep quality, depression, and quality of life in elderly hemodialysis patients.

Objective Both the incidence and the prevalence of end-stage renal disease (ESRD) in elderly patients are increasing worldwide. Elderly ESRD patients have been found to be more prone to depression than the general population. There are many studies that have addressed the relationship between sleep quality (SQ), depression, and health related quality of life (HRQoL) in ESRD patients, but previous studies have not confirmed the association in elderly hemodialysis (HD) patients. Therefore, the aim of the present study was to demonstrate this relationship in elderly HD patients. Patients and methods Sixty-three elderly HD patients (32 females and 31 males aged between 65 and 89 years) were included in this cross-sectional study. A modified Post-Sleep Inventory (PSI), the Medical Outcomes Study 36-item short form health survey, and the Beck Depression Inventory (BDI) were applied. Results The prevalence of poor sleepers (those with a PSI total sleep score [PSI-4 score] of 4 or higher) was 71% (45/63), and the prevalence of depression was 25% (16/63). Of the 45 poor sleepers, 15 had depression, defined as a BDI score of 17 or higher. Poor sleepers had a significantly higher rate of diabetes mellitus (P = 0.03), significantly higher total BDI scores, and lower Physical Component Scale scores (ie, lower HRQoL) than good sleepers. The PSI-4 score correlated negatively with Physical Component Scale (r = −0.500, P < 0.001) and Mental Component Scale scores (r = −0.527, P < 0.001) and it correlated positively with the BDI score (r = 0.606, P < 0.001). In multivariate analysis, independent variables of PSI-4 score were BDI score (beta value [β] = 0.350, P < 0.001), Mental Component Scale score (β = −0.291, P < 0.001), and age (β = 0.114, P = 0.035). Conclusion Poor SQ is a very common issue and is associated with both depression and lower HRQoL in elderly HD patients.

An Update on Coronary Artery Disease and Chronic Kidney Disease

Despite the improvements in diagnostic tools and medical applications, cardiovascular diseases (CVD), especially coronary artery disease (CAD), remain the most common cause of morbidity and mortality in patients with chronic kidney disease (CKD). The main factors for the heightened risk in this population, beside advanced age and a high proportion of diabetes and hypertension, are malnutrition, chronic inflammation, accelerated atherosclerosis, endothelial dysfunction, coronary artery calcification, left ventricular structural and functional abnormalities, and bone mineral disorders. Chronic kidney disease is now recognized as an independent risk factor for CAD. In community-based studies, decreased glomerular filtration rate (GFR) and proteinuria were both found to be independently associated with CAD. This paper will discuss classical and recent epidemiologic, pathophysiologic, and clinical aspects of CAD in CKD patients.

Coronary Flow Velocity Reserve and Carotid Intima Media Thickness in Patients with Autosomal Dominant Polycystic Kidney Disease: From Impaired Tubules to Impaired Carotid and Coronary Arteries

BACKGROUND AND OBJECTIVES Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease. Endothelial dysfunction, an early and reversible feature in the pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening, and increased intima-media thickness. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. The aim of the study was to investigate the carotid intima-media thickness and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Thirty normotensive patients with autosomal dominant polycystic kidney disease (10 male, 20 female) with well-preserved renal function and 30 healthy subjects (12 male, 18 female) were included in the study. Coronary flow velocity reserve was measured at baseline and after dipyridamole infusion by echocardiography. Coronary flow velocity reserve was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS Carotid intima-media thickness was significantly higher in patients than in control subjects (0.80 +/- 0.29 versus 0.54 +/- 0.14 mm, respectively; P < 0.001). Moreover, coronary flow velocity reserve was significantly lower in patients than in control subjects (1.84 +/- 0.39 versus 2.65 +/- 0.68, respectively; P < 0.001). CONCLUSIONS Normotensive patients with autosomal dominant polycystic kidney disease with well-preserved renal function have significantly increased carotid intima-media thickness and significantly decreased coronary flow velocity reserve compared with healthy subjects. These findings suggest that atherosclerosis starts at an early stage in the course of their disease in patients with autosomal dominant polycystic kidney disease.

Apoptosis and autophagy in cold preservation ischemia.

Background. Prolonged cold ischemia (CI) is a risk factor for the development of delayed graft function that predicts reduced 5-year kidney transplant survival. CI results in caspase-3 activation, tubular injury, and apoptosis. Autophagy, a highly conserved pathway that permits recycling of nutrients within the cell during stress, is linked to apoptosis. We hypothesized that CI during kidney preservation would induce autophagy. We sought to determine apoptosis and autophagic flux in CI. Methods. Autophagic flux and apoptosis were examined in kidneys of wild-type and green fluorescent protein (GFP)-microtubule-associated protein1 light chain 3 (LC3) transgenic mice that were subjected to 48 hr of CI. Autophagic flux was determined by performing experiments with and without bafilomycin A1. Results. CI alone significantly increased the number of apoptotic cells/hpf, caspase-3/7 activity, and protein expression of autophagy markers LC3 II and autophagy-related protein 5. To determine the effect of inhibiting autophagic flux on apoptosis, kidneys of wild-type and GFP-LC3 transgenic mice were subjected to 48 hr of CI in the presence of lysosomal inhibitor bafilomycin A1. The combination of CI and bafilomycin A1 suppressed autophagic flux and significantly reduced the number of apoptotic cells/hpf, caspase-3/7 activity, LC3 II (both by immunoblot and in GFP-LC3 transgenic mice), and autophagy-related protein 5 protein expression. Conclusion. In summary, we have shown that autophagy and autophagic flux are reduced in cold ischemic kidneys treated with bafilomycin A1. Reduced autophagy and autophagic flux were associated with a significant reduction in apoptotic cell death, which may provide a therapeutic rationale for including bafilomycin A1 in University of Wisconsin solution during organ preservation.