Ercan Ok

Publications (64)159.56 Total impact

• Article: The influence of dialysate calcium on progression of arterial stiffness in peritoneal dialysis patients.

  Meltem Sezis Demirci, Mehmet Ozkahya, Gulay Asci, Ebru Sevinc, Mumtaz Yilmaz, Cenk Demirci, Huseyin Toz, Ali Basci, Ercan Ok
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  ABSTRACT: One of the origins of cardiovascular disease in dialysis patients is arterial stiffness. The aim of our study was to assess the relationship between the calcium content of peritoneal dialysis (PD) solution and arterial stiffness. We enrolled into the study 49 PD patients who had been treated with the same PD solution for the preceding 6 months. The calcium content of the PD solution was 1.25 mmol/L in 34 patients (low-Ca group) and 1.75 mmol/L in 15 patients (high-Ca group). Study patients were followed for 6 months on the same PD prescription. Arterial stiffness was assessed by measurement of augmentation index (AI) and brachial pulse wave velocity (PWV) at baseline and at month 6 (SphygmoCor: Atcor Medical, West Ryde, NSW, Australia). Demographic data were recorded from patient charts. Mean age of the whole group was 51 +/- 11 years, prevalence of diabetes was 14%, duration of PD was 43 +/- 30 months, percentage of women was 45%, and percentage of patients using a cycler was 33%. We observed no differences between groups with regard to those variables or creatinine clearance, residual renal function, Ca, phosphorus, parathormone, C-reactive protein, lipid parameters, and use of phosphate binder with or without Ca content. Mean arterial pressure was higher in the high-Ca group, but the difference was not statistically significant (100 +/- 22 mmHg vs 88 +/- 18 mmHg, p = 0.06). At baseline, AI was significantly higher in the high-Ca group than in the low-Ca group (27% +/- 10% vs 21% +/- 9%, p < 0.05). Measurements of PWV were not different between the groups (8.4 +/- 1.1 m/s vs 8.5 +/- 1.7 m/s). Measurement of arterial stiffness parameters at month 6 revealed that PWV had increased in the high-Ca group (to 9.6 +/- 2.3 m/s from 8.4 +/- 1.1 m/s, p < 0.05), but had not changed in the low-Ca group (to 8.2 +/- 1.9 m/s from 8.5 +/- 1.7 m/s). The AI did not change in either group. These data suggest that Ca exposure through PD solution plays a role in the progression of arterial stiffness, which may be related to increased vascular calcification.
  Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 02/2009; 29 Suppl 2:S15-7. · 2.10 Impact Factor
• Article: Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.

  Gulay Asci, Ali Basci, Sudhir V Shah, Alexei Basnakian, Huseyin Toz, Mehmet Ozkahya, Soner Duman, Ercan Ok
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  ABSTRACT: Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC). Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied. Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis. The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.
  Nephrology 12/2008; 13(6):480-6. · 1.31 Impact Factor
• Article: The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis.

  Meral Kayikcioglu, Murat Tumuklu, Mehmet Ozkahya, Oner Ozdogan, Gulay Asci, Soner Duman, Huseyin Toz, Levent H Can, Ali Basci, Ercan Ok
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  ABSTRACT: Most haemodialysis (HD) centres use anti-hypertensive drugs for the management of hypertension, whereas some centres apply dietary salt restriction strategy. In this retrospective cross-sectional study, we assessed the effectiveness and cardiac consequences of these two strategies. We enrolled all patients from two dialysis centres, who had been on a standard HD programme at the same centre for at least 1 year. All patients underwent echocardiographic evaluation. Clinical data were obtained from patients' charts. Centre A (n = 190) practiced 'salt restriction' strategy and Centre B (n = 204) practiced anti-hypertensive-based strategy. Salt restriction was defined as managing high blood pressure (BP) via lowering dry weight by strict salt restriction and insistent ultrafiltration without using anti-hypertensive drugs. There was no difference regarding age, gender, diabetes, history of cardiovascular disease and efficiency of dialysis between centres. Antihypertensive drugs were used in 7% of the patients in Centre A and 42% in Centre B (P < 0.01); interdialytic weight gain was significantly lower in Centre A (2.29 +/- 0.83 kgversus 3.31 +/- 1.12 kg, P < 0.001). Mean systolic and diastolic blood pressures were similar in the two centres. However, Centre A had lower left ventricular (LV) mass (indexed for height(2.7): 59 +/- 16 versus 74 +/- 27 g/m(2.7), P < 0.0001). The frequency of LV hypertrophy was lower in Centre A (74% versus 88%, P < 0.001). Diastolic and systolic functions were better preserved in Centre A. Intradialytic hypotension (hypotensive episodes/100 patient sessions) was more frequent in Centre B (11 versus 27, P <0.01). This cross-sectional study suggests that salt restriction and reduced prescription of antihypertensive drugs may limit LV hypertrophy, better preserve LV functions and reduce intradialytic hypotension in HD patients.
  Nephrology Dialysis Transplantation 12/2008; 24(3):956-62. · 3.40 Impact Factor
• Article: The long forgotten salt factor.

  Stanley Shaldon, Mehmet Ozkahya, Ercan Ok, Ali Basci, Evert J Dorhout Mees
  Kidney International 11/2008; 74(7):963-4; author reply 964-5. · 6.61 Impact Factor
• Article: Interdialytic blood pressure obtained by ambulatory blood pressure measurement and left ventricular structure in hypertensive hemodialysis patients.

  Siddig Mominadam, Mehmet Ozkahya, Meral Kayikcioglu, Huseyin Toz, Gulay Asci, Soner Duman, Pinar Ergin, Sait Kirbiyik, Ercan Ok, Ali Basci
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  ABSTRACT: Unlike in subjects with normal renal function, the relationship between hypertension and cardiovascular morbidity and mortality in dialysis patients is still being debated. In order to clarify this issue, we performed 44-hour ambulatory blood pressure measurements (ABPM) during the interdialytic period in a group of 164 hypertensive patients, the blood pressure (BP) control based on conventional antihypertensive strategy previously, on chronic hemodialysis treatment in the Mediterranean region of Turkey. These results were then compared with their echocardiographic data. This is a cross-sectional analysis. The mean ABPM during 44 hours was close to the manually measured predialysis value, but there was a gradual increase in the ABPM values in the interdialytic period. When divided into a group with mild or no left ventricular hypertrophy (LVH) (45 patients) and severe LVH (119 patients), the latter had significantly higher BP levels in all separate periods, while the difference in predialysis BP was not significant. Patients with severe LVH had larger left atrium and left ventricular diameters, and consumed more antihypertensive drugs. Systolic BP during the night before dialysis showed the strongest relation to LVH, but interdialytic weight gain was also independently related to LVH. Yet, 56% of the patients with systolic BP <135 had severe LVH. There is not only an association between BP and presence of LVH, but it is shown that volume expansion is also an important independent determinant of LVH. This may explain the difficulty in identifying hypertension as a cardiac risk factor in these patients.
  Hemodialysis International 07/2008; 12(3):322-7. · 1.54 Impact Factor
• Article: Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model.

  Soner Duman, Devrim Bozkurt, Savas Sipahi, Murat Sezak, Sultan Ozkan, Muhittin Ertilav, Sait Sen, Ercan Ok
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  ABSTRACT: The most serious complication of peritoneal dialysis is encapsulating peritoneal sclerosis (EPS). The prolonged inflammatory stimuli, fibrogenic cytokine overexpression, and angiogenesis that underlie EPS ultimately result in increased production of fibrous tissue, encapsulating the bowel loops. In recent years, inhibitors of mammalian target of rapamycin (mTOR) as an alternative agent for calcineurin inhibitor toxicity have been widely used in organ transplantation. These agents have also been used since the 1990s in endovascular medicine for drug-eluting stents because of antiproliferative effects on vascular smooth muscle cells and potent anti-inflammatory properties by direct action on human immune cells. Because of the shared characteristics of EPS and other fibrotic processes, we hypothesized that everolimus, an mTOR inhibitor can reverse the process responsible for the eventual development of EPS. We allocated 32 non-uremic albino Wistar rats to 4 groups: control group, 2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group, 2 mL/200 g (0.1%) chlorhexidine gluconate (CG) injected IP daily and ethanol (15%) dissolved in saline, for 3 weeks; resting group, CG (weeks 0 - 3), plus peritoneal rest (weeks 3 - 6); and Evo-R, CG (weeks 0 - 3), plus 0.3 mg/L everolimus in drinking water (weeks 3 - 6). At the end of the study, we performed a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution, and examined the dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell count, ultrafiltration (UF) volume, and morphologic change in the parietal peritoneum. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, p < 0.05). Peritoneal rest has some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However; everolimus was more effective than peritoneal rest with regard to vascularity and peritoneal thickness (p < 0.05). Everolimus has beneficial effects on UF failure, inflammation, and fibrosis. Everolimus may have therapeutic value in the management of EPS.
  Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 02/2008; 24:104-10.
• Article: Rosiglitazone, a peroxisome proliferator-activated receptor agonist, improves peritoneal alterations resulting from an encapsulated peritoneal sclerosis model.

  Devrim Bozkurt, Hüseyin Taskin, Murat Sezak, Selahattin Biçak, Sait Sen, Ercan Ok, Soner Duman
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  ABSTRACT: Inflammation, fibrosis, and angiogenesis underlie the pathophysiology of encapsulating peritoneal sclerosis (EPS). The irreversible sclerosis of visceral and parietal peritoneum that characterizes EPS can be seen in peritoneal dialysis (PD) patients after long periods on dialysis. Peroxisome proliferator-activated receptors (PPARs) are the major regulator of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The aim of the present study was to investigate the effect of the PPAR agonist rosiglitazone on the progression and regression of peritoneal alterations in chlorhexidine gluconate-induced EPS in rats. We divided 53 nonuremic Wistar albino rats into 5 groups: control group--isotonic saline 2 mL, injected intraperitoneally (IP) daily for 3 weeks; chlorhexidine gluconate (CG) group--CG 2 mL per 200 g body weight, injected IP daily for 3 weeks; Rozi-P group--CG injection as described, plus rosiglitazone in drinking water (8 mg/L) for 3 weeks; resting group--CG injection as described during weeks 1 - 3, then peritoneal rest during weeks 4 - 6; Rozi-R group--CG injection as described during weeks 1 - 3, then rosiglitazone in drinking water (8 mg/L) during weeks 4 - 6. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed with 25 mL 3.86% glucose PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell (WBC) count, ultrafiltration (UF) volume, and morphology change in parietal peritoneum were examined. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, both p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, all p < 0.05). Peritoneal rest had some advantages in UF failure and WBC count only (both p < 0.05). However, rosiglitazone was more effective than peritoneal rest for vascularity and peritoneal thickness (p < 0.05). We suggest that the PPAR agonist rosiglitazone may have a therapeutic value in the management of EPS by inhibiting inflammation and neovascularization.
  Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 02/2008; 24:32-8.
• Article: Novel mechanisms in accelerated atherosclerosis in kidney disease.

  Sudhir V Shah, Eugene O Apostolov, Ercan Ok, Alexei G Basnakian
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  ABSTRACT: Urea undergoes a spontaneous, nonenzymatic transformation to cyanate, the active part of which is isocyanic acid, which can cause modifications of a variety of proteins in a process called carbamylation. We postulated that, in patients with renal disease, the carbamylation of low-density lipoprotein (LDL) is a nontraditional risk factor for cardiovascular disease, and that elevated urea leads to carbamylated LDL (cLDL), which causes vascular injury and leads to atherosclerosis. We showed that carbamylated LDL manifests all of the biological effects relevant to atherosclerosis, including endothelial-cell injury, the expression of adhesion molecules, and vascular smooth muscle cell proliferation. We also developed an enzyme-linked immunosorbent assay to measure carbamylated LDL in patients, and showed that cLDL is markedly elevated in dialysis patients. Our data indicate that cLDL may be an important nontraditional risk factor for atherosclerosis in patients with kidney disease.
  Journal of Renal Nutrition 02/2008; 18(1):65-9. · 1.57 Impact Factor
• Article: Modified LDLs induce proliferation-mediated death of human vascular endothelial cells through MAPK pathway.

  Eugene O Apostolov, Alexei G Basnakian, Xiaoyan Yin, Ercan Ok, Sudhir V Shah
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  ABSTRACT: The ability of modified low-density lipoptoteins (LDLs) to induce both proliferation and death of endothelial cells is considered to be a mechanism of early atherosclerosis development. We previously showed that carbamylated LDL (cLDL) induces human coronary artery endothelial cell (HCAEC) death in vitro. This effect is similar to the atherogenic action of oxidized LDL (oxLDL) that induces the proliferation and death of endothelial cells. The present study was designed to analyze a potential proliferative effect of cLDL and whether proliferation caused by modified LDLs is related to cell death. Cultured HCAECs were exposed to different concentrations of modified LDL or native LDL for varying periods of time. Cell proliferation measured by bromodeoxyuridine incorporation and S-phase analysis was dose-dependently increased in the presence of cLDL (6.25-200 microg/ml). The proliferation induced by cLDL or oxLDL was associated with cell death and increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK). Inhibition of cLDL- or oxLDL-induced proliferation by aphidicolin (1 microg/ml) was protective against both short-term cell death measured by lactate dehydrogenase release into the medium and long-term cell viability visualized by cell multiplication. Inhibition of ERK phosphorylation led to a significant decrease of DNA synthesis and cell rescue from injury by modified LDLs, while inhibition of JNK phosphorylation had an only partial rescue effect without involvement in cell proliferation. These data are the first evidence that endothelial cell death induced by cLDL or oxLDL is mediated by cell proliferation through the mitogen-activated protein kinase pathway.
  AJP Heart and Circulatory Physiology 05/2007; 292(4):H1836-46. · 3.71 Impact Factor
• Source

  Available from: ahajournals.org

  Article: Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.

  Eugene O Apostolov, Sudhir V Shah, Ercan Ok, Alexei G Basnakian
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  ABSTRACT: Carbamylated low-density lipoprotein (LDL), the most abundant modified LDL isoform in human blood, has been recently implicated in causing the atherosclerosis-prone injuries to endothelial cells in vitro and atherosclerosis in humans. This study was aimed at testing the hypothesis that carbamylated LDL acts via inducing monocyte adhesion to endothelial cells and determining the adhesion molecules responsible for the recruitment of monocytes. Exposure of human coronary artery endothelial cells with carbamylated LDL but not native LDL caused U937 monocyte adhesion and the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 adhesion molecules as measured by cell enzyme-linked immunosorbent assay. Silencing of intercellular adhesion molecule-1 by siRNA or its inhibition using neutralizing antibody resulted in decreased monocyte adhesion to the endothelial cells. Similar silencing or neutralizing of vascular cell adhesion molecule-1 alone did not have an effect but was shown to contribute to intercellular adhesion molecule-1 when tested simultaneously. Taken together, these data provide evidence that intercellular adhesion molecule-1 in cooperation with vascular cell adhesion molecule-1 are essential for monocyte adhesion by carbamylated low-density lipoprotein-activated human vascular endothelial cells in vitro.
  Arteriosclerosis Thrombosis and Vascular Biology 05/2007; 27(4):826-32. · 6.37 Impact Factor
• Article: Improvement in "uremic" cardiomyopathy by persistent ultrafiltration.

  Hüseyin Töz, Mehmet Ozkahya, Filiz Ozerkan, Gülay Aşçi, Ercan Ok
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  ABSTRACT: Some patients with end-stage renal disease suffer severe cardiac dilatation with functional disturbances, notably low ejection fraction (EF) and valvular regurgitation. They often have normal or low blood pressure, and tolerate ultrafiltration (UF) poorly. The aim of our study was to investigate to what extent this condition can still be improved by persistent slow UF. Twelve patients with cardiothoracic index >0.54 and EF <0.45 but otherwise uncomplicated were treated by slow, prolonged UF during hemodialysis (3 times a week) sessions, if necessary supplemented by isolated UF sessions on a separate day. Repeated chest X-rays and Doppler echocardiography were applied. During treatment periods varying from 20 to 120 days, all of the patients lost weight (12+/-10 kg) and became edema free. Cardiothoracic index decreased in all patients from a mean of 0.59+/-0.04 to 0.47+/-0.03. Blood pressure decreased when it had been elevated and increased when it was below normal. Ejection fraction increased in all of them from a mean of 0.31+/-0.9 to 0.50+/-0.9. Mitral and tricuspid regurgitation were found in every patient and disappeared or improved in all of them. Striking improvement of cardiac dilatation and dysfunction can be achieved by carefully monitored persistent UF in the majority of patients with seemingly intractable dilated cardiomyopathy.
  Hemodialysis International 01/2007; 11(1):46-50. · 1.54 Impact Factor
• Article: Long-term survival rates in haemodialysis patients treated with strict volume control.

  Mehmet Ozkahya, Ercan Ok, Huseyin Toz, Gulay Asci, Soner Duman, Ali Basci, Timur Kose, E J Dorhout Mees
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  ABSTRACT: We analysed the survival of 218 patients (132 male, 86 female, age 48 +/- 15 years) who were treated in our dialysis units since we adopted the strategy of strict volume control without antihypertensive drugs. The mean observation period was 47 +/- 34 (6-140) months. Follow-up was ended because of death (57 patients), transfer to another center (35 patients), continous ambulatory peritoneal dialysis (CAPD) (15 patients) or transplantation (23 patients), while 88 were still under our treatment at the time of writing. Blood pressure (BP) decreased from a mean of 150 +/- 31/89 +/- 16 at the start to 121 +/- 14/75 +/- 8 mmHg at the end of observation (P < 0.001). Only nine patients needed a drug (enalapril) to reach this goal. Cardiothoracic index (CTI) dropped from 0.50 +/- 0.06 to 0.46 +/- 0.05 (P < 0.001). Interdialytic weight gain decreased from 1440 +/- 360 to 930 +/- 240 g/day (P < 0.001). Mortality rate was 68, 2 per 1000 patient-years, better than in most published series. There was a striking influence of age, but also of CTI and systolic BP on survival rate. Patients with CTI > or = 0.48 showed mortality 3.8 times higher than CTI < 0.48 (log rank P < 0.001). Consequently, the mean CTI of the deceased patients was much higher (0.50) than the average of the group (0.46) while their mean BP (123 +/- 16/75 +/- 9 mmHg) was not significantly different from the other patients. We found no increased mortality at low-normal pressure levels (systolic BP between 100 and 130 mmHg), but mortality was increased in small groups of patients whose pressures were lower or higher than these values. Thus, the curve, relating mortality to blood pressure was shifted markedly to the left. These results strongly suggest that the strategy of 'volume control', also when applied with conventional dialysis times, normalizes BP and increases survival of dialysis patients. Cardiomegaly, as evidenced on the chest X-ray despite normal BP, had a strong negative influence on survival. The large majority of the patients had low-normal BP after long periods of treatment and showed the lowest mortality, favouring the view that target BP should be lower than advised by most authors.
  Nephrology Dialysis Transplantation 01/2007; 21(12):3506-13. · 3.40 Impact Factor
• Source

  Available from: Fatih Kircelli

  Article: What does peritoneal thickness in peritoneal dialysis patients tell us?

  Soner Duman, Suha Sureyya Ozbek, Ebru Sevinc Gunay, Devrim Bozkurt, Gulay Asci, Savas Sipahi, Fatih Kirçelli, Muhittin Ertilav, Mehmet Ozkahya, Ercan Ok
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  ABSTRACT: Loss of peritoneal function is a major factor leading to failure of treatment in peritoneal dialysis (PD). Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. The aim of the present study was to uncover the relationship between functional parameters of peritoneum and peritoneal thickness as measured by ultrasonography. We studied 43 prevalent patients who had been on PD for at least 12 months in the Ege University PD unit. We recorded body weight, height, age, sex, PD duration, episodes of peritonitis, and results of peritoneal equilibration tests. Parietal peritoneal thickness was measured from four abdominal quadrants at the mid-clavicular line. The peritoneal thickness measurement was determined as the mean of the four separate measurements. (In some cases, the measurement at one of the lower quadrants was excluded from the calculation if the peritoneal catheter was present near the area probed.) Mean peritoneal thickness in the patients was 446 +/- 164 microm (range: 250-930 microm), which was significantly correlated with mean body weight (r = 0.31, p < 0.05), height (r = 0.31, p < 0.05), end-to-initial ratio of dialysate glucose (r = -0.44, p < 0. 01), dialysate-to-plasma creatinine (r = 0.51, p < 0.01), and PD duration (r = 0.48, p < 0.01). Peritoneal thickness was positively correlated with time on dialysis, being a median of 370 microm [interquartile range (IQR): 283-400 microm] in patients who had been on PD for less than 24 months up and 660 microm (IQR: 483-733 microm) in patients who had undergone PD for more than 6 years. Ultrasound examination is a simple and noninvasive method of measuring peritoneal thickness in PD patients. It may be useful in the study of peritoneal structure and function. Sequential measurements over time may be useful for early diagnosis of encapsulating peritoneal sclerosis.
  Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2007; 23:28-33.
• Article: Oral-facial-digital syndrome type 1, Caroli's disease and cystic renal disease.

  Omer Toprak, Atilla Uzum, Mustafa Cirit, Ertap Esi, Ayca Inci, Rifki Ersoy, Mehmet Tanrisev, Ercan Ok, Brunella Franco
  Nephrology Dialysis Transplantation 07/2006; 21(6):1705-9. · 3.40 Impact Factor
• Article: Carbamylated low-density lipoprotein induces death of endothelial cells: a link to atherosclerosis in patients with kidney disease.

  Ercan Ok, Alexei G Basnakian, Eugene O Apostolov, Yousri M Barri, Sudhir V Shah
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  ABSTRACT: The presence of accelerated atherosclerosis in patients with kidney disease cannot be entirely explained by traditional cardiovascular risk factors. Exposure to urea, which is normally present in human blood plasma and elevated in patients with kidney disease, leads to the carbamylation of proteins. We postulated that low-density lipoprotein (LDL) carbamylated by urea has biologic effects relevant to atherosclerosis. To produce carbamylated LDL (cLDL), human native LDL (nLDL) was chemically modified in vitro by exposure to potassium cyanate. Human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (CASMCs) were treated in vitro with cLDL or nLDL. Irreversible cell death was measured using the lactate dehydrogenase (LDH) assay, apoptosis was assessed by annexin V binding, and proliferation was determined using bromodeoxyuridine (BrdU) incorporation. Total plasma protein carbamylation and plasma cLDL were measured in hemodialysis patients using the homocitrulline assay and enzyme-linked immunosorbent assay (ELISA). Our studies demonstrated that cLDL but not nLDL induced dose-dependent vascular cell injuries relevant to atherosclerosis, which included the proliferation of vascular smooth muscle cells and endothelial cell death. Under light microscopy, endothelial cells treated with cLDL showed signs of morphologic alterations. The injury to endothelial cells measured by LDH release was time-dependent and correlated with the degree of LDL carbamylation. At least a part of the endothelial cell population treated with cLDL died by apoptosis. In patients with advanced renal disease on hemodialysis, total plasma protein carbamylation and plasma cLDL were several times higher than in control healthy individuals. Collectively these data suggest the potential role of carbamylated LDL in accelerated atherosclerosis in patients with chronic renal disease and, possibly, in healthy individuals.
  Kidney International 08/2005; 68(1):173-8. · 6.61 Impact Factor
• Article: Quantification of carbamylated LDL in human sera by a new sandwich ELISA.

  Eugene O Apostolov, Sudhir V Shah, Ercan Ok, Alexei G Basnakian
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  ABSTRACT: We previously suggested that increased carbamylated LDL (cLDL), a product of nonenzymatic modification of LDL in human serum by urea-derived cyanate, may cause cardiovascular complications in patients with chronic renal insufficiency. An assay for precise measurement of cLDL in serum was not previously available. Polyclonal antibodies against human cLDL and nonmodified, native LDL (nLDL) were raised in rabbits and extensively purified by affinity chromatography. New sandwich ELISAs to measure cLDL and nLDL with use of these antibodies were developed. Serum concentrations of cLDL and nLDL were measured by the sandwich ELISAs in 41 patients with end-stage renal disease (ESRD) and 40 healthy controls. Both assays showed satisfactory reproducibility, linearity, and recovery. The assays could detect 2.7 mg/L cLDL with a linear detection range of 5-1000 mg/L and 5 mg/L nLDL with a linear detection range of 50-1000 mg/L. These measurements showed that patients with ESRD have significantly increased serum cLDL [281.5 (46.9) mg/L compared with 86.1 (29.7) mg/L in a control group; P <0.001]. There was no significant difference in nLDL concentrations between the groups. These assays are a potentially valuable tool for cardiovascular research in renal patients and healthy individuals. The cLDL concentration appears to be the highest among all previously described modified LDL isoforms in both controls and ESRD patients.
  Clinical Chemistry 05/2005; 51(4):719-28. · 7.91 Impact Factor
• Article: Scintigraphic diagnosis of protein-losing enteropathy secondary to amyloidosis.

  Ayşegül Akgün, Ebru Tani Acar, Memduh Sami Taner, Zehra Ozcan, Ercan Ok
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  ABSTRACT: Protein-losing enteropathy is an uncommon syndrome of excessive loss of protein via the gastrointestinal mucosa. 99mTc-dextran scintigraphy was performed on a 42-year-old woman with protein-losing enteropathy. She had secondary amyloidosis due to rheumatoid arthritis. Abnormal leakage of the radiotracer was observed in the mid-abdominal region suggesting the site of protein loss. It is concluded that 99mTc-dextran scintigraphy is useful as a noninvasive and simple test for the imaging and confirmation of diagnosis in protein-losing enteropathy.
  The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 04/2005; 16(1):41-3. · 0.47 Impact Factor
• Article: Patients with failed renal transplant may be suitable for peritoneal dialysis.

  Soner Duman, Gülay Aşçi, Hüseyin Töz, Mehmet Ozkahya, Muhittin Ertilav, Meltem Seziş, Ercan Ok
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  ABSTRACT: It has been claimed that patients with late transplant failure returning to peritoneal dialysis have lower patient and technique survival. In this retrospective study, we aimed to clarify this issue in a large PD population. Thirty-four PD patients with a failed renal transplant (FTx) and 82 PD patients who had never received a kidney transplant (Non-Tx) or HD treatment were investigated. All fTx patients were using only steroids (5-10 mg/day) for first 3 months of peritoneal dialysis. The groups were similar regarding to age, sex, residual renal function and KT/V; none of them was diabetic. Ftx group had a higher number of peritonitis attack than Non-Tx group (2.42 +/- 0.41 v 1.61 +/- 0.15, attack per patient, p = 0.013). PET status was not different. One, 3 and 5 year patient survival calculated with the Kaplan Meier method were 93%; 93%; 93% respectively in Ftx and 97%; 89%; 82% respectively in Non-Tx patients. Technique survival was 83%; 77%; 60% in Ftx and 91%; 64%; 48% in Non-Tx patients respectively. We conclude that PD appears to be a good option for fTx patients. A previous renal transplantation does not adversely affect patient and technique survival. Although the somewhat higher infection risk is of some concern, we did not observe earlier loss of peritoneal functions (high transporter) in the post transplant patients.
  International Urology and Nephrology 02/2004; 36(2):249-52. · 1.47 Impact Factor
• Article: GB virus C/hepatitis G virus infection among renal transplant recipients in Izmir, Turkey: Molecular analysis of phylogenetic groups.

  Selda Erensoy, Aysin Zeytinoglu, Servet Göksel, Tijen Ozacar, Mehmet Ozkahya, Ercan Ok, Salih Tuumlrkoglu, Altinay Bilgiç
  International Journal of Infectious Diseases 10/2002; 6(3):242-3. · 1.94 Impact Factor
• Article: Successful treatment of post-transplant Kaposi's sarcoma by reduction of immunosuppression.

  Soner Duman, Hüseyin Töz, Gülay Aşçi, Sibel Alper, Mehmet Ozkahya, Idil Unal, Ali Celik, Ercan Ok, Ali Başçi
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  ABSTRACT: The aim of this study was to investigate retrospectively the clinical presentation, the efficacy of reducing immunosuppression and the consequences of this therapeutic approach in Kaposi's sarcoma (KS) developing after renal transplantation. We reviewed the records of 502 patients who had been followed up at our transplantation unit between October 1, 1987 and December 30, 1998. Twelve patients (2.4%) with KS were included in the study. The mean age of KS patients was 38+/-11 years (one female, 11 males). All were on prednisone, azathioprine (AZT) and cylcosporin treatment. KS was encountered at a mean of 18+/-10 months post-renal transplantation. Typical Kaposi's lesions were present in the skin of 11 out of l2 patients. In the only patient without skin involvement, who died from haemophagocytic histiocytic syndrome caused by septicaemia, KS was diagnosed post-mortem in a lymph node. In five patients only skin involvement was present, while the others also had visceral involvement (oropharynx in two patients, trachea and lung in three, lymph node in two, stomach and duodenum in two). Cyclosporin was stopped within 1 month after KS diagnosis, and AZT was stopped in three patients. Both cutaneous and visceral KS manifestations disappeared and no patient was lost due to KS. During a follow-up period 46+/-19 months, KS recurred in the lungs in one patient together with lung tuberculosis, while he was on prednisone and AZT. Two patients lost their graft due to chronic rejection. The remaining eight patients currently have a functioning graft with a mean creatinine level of 1.4+/-0.5 mg/dl. KS is the most frequent post-transplant neoplasia (80%) in our country. In the present study cohort, half of the patients had visceral involvement. Reduction or discontinuation of immunosuppression caused complete remission in all patients without surgical intervention, chemotherapy or radiotherapy.
  Nephrology Dialysis Transplantation 06/2002; 17(5):892-6. · 3.40 Impact Factor