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    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, Kultigin
    The 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.
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    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, Erkan
    Background/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
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    The Relationship of Red-Cell Distribution Width and Carotid Intima Media in Chronic Kidney Disease
    (Turk Nefroloji Diyaliz Transplantasyon Dergisi, 2016) Guclu, Aydin; Tokmak, Turgut Tursem; Kaymaz, Haci; Turkmen, Kultigin; Senol, Hande; Ozhan, Nail; Dursun, Yusuf
    OBJECTIVE: Red-cell distribution width (RDW) is a parameter routinely used for diagnosis of different anemia types. Recent studies have shown the RDW relationship with mortality in general population and patients with cardiovascular disease. However, the number of studies on RDW in chronic kidney disease (CKD) is insufficient. We evaluated the relationship between RDW and carotid intima media thickness (IMT), which is a predictor of atherosclerosis, in patients with CKD. MATERIAL and METHODS: 30 healthy controls, 30 patients with CKD, 37 hemodialysis patients were included. IMT was measured with ultrasonography. RESULTS: We identified statistically significant differences in CRP (p: 0.039), hemoglobin (p< 0.001), IMK (p< 0.001), RDW (p< 0.001), urea (p< 0.001), creatinine (p< 0.001), albumin (p< 0.001), uric acid (p< 0.001) and ferritin (p< 0.001) levels among three groups. In post hoc analysis, the IMK value was statistically significantly higher in the predialysis (p< 0.001) and hemodialysis group than healthy controls. IMK value was not statistically different in the hemodialysis group than the predialysis group (p: 0.988). The RDW value was higher in the predialysis group than controls with a trend to statistical significance (p: 0.067). RDW value showed positive correlation with IMK (r: 0.356 P: 0.012) and CRP (r: 0.361 P: 0.004). CONCLUSION: RDW is associated with inflammation and intima media thickness in patients with CKD.