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Öğe Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus(Wolters Kluwer Medknow Publications, 2016) Demirtas, Levent; Guclu, Aydin; Erdur, Fatih Mehmet; Akbas, Emin Murat; Ozcicek, Adalet; Onk, Didem; Turkmen, KultiginThe prevalence of diabetes mellitus (DM) is increasing secondary to increased consumption of food and decreased physical activity worldwide. Hyperglycaemia, insulin resistance and hypertrophy of pancreatic beta cells occur in the early phase of diabetes. However, with the progression of diabetes, dysfunction and loss of beta cells occur in both types 1 and 2 DM. Programmed cell death also named apoptosis is found to be associated with diabetes, and apoptosis of beta cells might be the main mechanism of relative insulin deficiency in DM. Autophagic cell death and apoptosis are not entirely distinct programmed cell death mechanisms and share many of the regulator proteins. These processes can occur in both physiologic and pathologic conditions including DM. Besides these two important pathways, endoplasmic reticulum (ER) also acts as a cell sensor to monitor and maintain cellular homeostasis. ER stress has been found to be associated with autophagy and apoptosis. This review was aimed to describe the interactions between apoptosis, autophagy and ER stress pathways in DM.Öğe Atrial electromechanical delay and left atrial mechanical functions in hemodialysis and peritoneal dialysis patients(Springer, 2016) Demirtas, Levent; Turkmen, Kultigin; Buyuklu, Mutlu; Kocyigit, Ismail; Orscelik, OzcanLeft atrium (LA) mechanical functions and atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity in general population. Data are scant about these parameters in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We aimed to evaluate AEMD times and LA mechanical functions and associated risk factors in HD and PD patients. Forty-four healthy individuals, 62 HD and 50 PD patients were enrolled in the study. Echocardiography was performed before midweek dialysis session for HD patients and on admission for PD patients. Data were expressed as mean +/- A SD. Spearman's test was used to assess linear associations. Predictors of left intra-atrial EMD time and LA active emptying volume (LAaeV) were assessed by regression analysis. Left intra-atrial-AEMD times were significantly longer in HD patients compared to PD patients. LAaeV was positively correlated with inter-atrial time, left intra-atrial time, systolic and diastolic BP, calcium and neutrophil-to-lymphocyte ratio (NLR) (r 0.22, p 0.016; r 0.28, p 0.002; r 0.34, p < 0.001; r 0.35, p < 0.001; r 0.37, p < 0.001; r 0.46, p < 0.001, respectively) and negatively correlated with serum uric acid (r -0.31, p 0.013) in ESRD patients. We found positive correlations between left intra-atrial time and LAaeV, LAV(max), LAV(p) and NLR (r 0.28, p 0.002; r 0.27, p 0.003; r 0.27, p 0.003; r 0.22, p 0.03, respectively) and negative correlations with albumin, uric acid and potassium (r -0.24, p 0.008; r -0.19, p 0.04; r -0.26, p 0.037, respectively). Advanced age, decreased serum albumin and increased NLR were found to be independent predictors of LAaeV; however, only NLR was found to be an independent predictor of AEMD time in this population. Increased inflammation might be a risk factor of AEMD and LA mechanical dysfunction in ESRD patients.Öğe The effect of Ramadan fasting on kidney function in patients with chronic kidney disease(Springer, 2020) Baloglu, Ismail; Turkmen, Kultigin; Kocyigit, Ismail; Altunoren, Orcun; Demirtas, Levent; Zararsiz, Gokmen; Eroglu, ErayPurpose Because of the increase in globalization, clinicians all over the world are confronted the questions about safety of Ramadan fasting. However, there is no clear information about whether there is an obstacle for fasting patients with chronic disease. Hence, in the present study, we aimed to investigate the effects of Ramadan fasting on kidney and the factors affecting this relationship in patients with chronic kidney disease. Methods This study involving 117 patients [36 females, 81 males; mean age, 60 (46.0-70.0) years] with stage 2-3 chronic kidney and fasting. Patients were evaluated every 10 days for acute kidney injury (AKI) in Ramadan month. And, patients with acute kidney injury and patients without AKI were grouped. Results When the patients were evaluated for AKI, we observed that in 27 patients had acute kidney injury. While patients without AKI fasted for more days (p < 0.001), urea levels and frequency of hypertension were higher in the group with AKI (p = 0.019;p = 0.025 respectively). We also performed univariate and multiple binary logistic regression analysis to identify the risk factors of AKI. Hypertension and number of fasting day were found to be predictive of AKI (p = 0.02;p < 0.001 respectively). Conclusions We found a significant relationship between hypertension, the number of fasting days and acute kidney injury. Patients with chronic kidney damage and hypertension should be evaluated more carefully, informed about the importance of hydration after fasting and should be followed frequently for AKI.Öğe Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients(Wiley, 2013) Turkmen, Kultigin; Erdur, Fatih Mehmet; Ozcicek, Fatih; Ozcicek, Adalet; Akbas, Emin Murat; Ozbicer, Aysu; Demirtas, LeventNeutrophil-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- (TNF-) 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-, IL-6 levels were measured. PLR, NLR, serum high sensitive C-reactive protein, IL-6, and TNF- levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR140 had significantly higher NLR, IL-6, and TNF- levels when compared to patients with PLR<139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL-6, and TNF- 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- (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.Öğe The possible role of interleukin-33 as a new player in the pathogenesis of contrast-induced nephropathy in diabetic rats(Taylor & Francis Ltd, 2016) Demirtas, Levent; Turkmen, Kultigin; Kandemir, Fatih Mehmet; Ozkaraca, Mustafa; Kucukler, Sefa; Gurbuzel, Mehmet; Comakli, SelimIntroduction: Patients with diabetic kidney disease (DKD) are more prone to contrast-induced nephropathy (CN). Apoptosis and autophagy were found to be essential in the pathogenesis of DKD. Interleukin-33 (IL-33) is a cytokine, but its role in DKD and CN is unknown. As IL-33 is modulated by apoptosis, we aimed to determine the relationship between IL-33 apoptosis and autophagy in DKD with CN. Materials and methods: Thirty male Sprague-Dawley rats were enrolled and randomly allocated into three groups. The first group was comprised of healthy rats (HRs), whereas the other two groups were made up of diabetic rats (DRs) and diabetic rats with CN (DRs+CN). All groups except the HRs received 50mg/kg/day of streptozotocin (STZ). The DRs+CN group was induced by administering 1.5mg/kg of intravenous radiocontrast dye on the 35th day. Results: We observed increased IL-33 in the kidney tissue following induction of CN in the DRs. The DRs showed moderate immunopositivity, and the DRs+CN showed severe immunopositivity for caspase-3, cleaved caspase-3, caspase-8, caspase-9, LC3B, and Beclin-1 in tubular cells and glomeruli. The DRs also showed moderate immunopositivity in tubular cells, and the DRs+CN group showed severe immunopositivity for IL-33 in tubular cells. Increased caspase-3 was found in both glomeruli and tubuli; however, we could not demonstrate IL-33 in glomeruli. This could be secondary to inactivation of IL-33 via increased caspase-3 activity. Conclusion: The release of IL-33 from necrotic cells might induce autophagy, which can further balance the effects of increased apoptosis secondary to CN in DKD.Öğe PREDICTORS OF ATRIAL CONDUCTION DELAY IN HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS: THE ROLE OF INFLAMMATION(Oxford Univ Press, 2015) Turkmen, Kultigin; Demirtas, Levent; Akbas, Emin M.; Buyuklu, Mutlu; Bakirci, Eftal; Kocyigit, Ismail; Orscelik, Ozcan[Abstract Not Availabe]Öğe PREDICTORS OF LEFT ATRIAL MECHANICAL FUNCTIONS IN END STAGE RENAL DISEASE PATIENTS(Oxford Univ Press, 2015) Turkmen, Kultigin; Demirtas, Levent; Buyuklu, Mutlu; Kocyigit, Ismail; Kocyigit, Ismail; Orscelik, Ozcan[Abstract Not Availabe]Öğe The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study(Karger, 2016) Turkmen, Kultigin; Guclu, Aydin; Sahin, Garip; Kocyigit, Ismail; Demirtas, Levent; Erdur, Fatih Mehmet; Sengul, ErkanBackground/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of a-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed a-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fa bry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. (C) 2016 The Author(s) Published by S. Karger AG, Basel
