Berna Yelken

Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease.

BACKGROUND Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the nonuremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. METHODS In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. RESULTS Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001). CONCLUSION Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.

Coronary artery calcification and coronary flow velocity in haemodialysis patients

BACKGROUND Decreased coronary flow reserve (CFR) is a marker of endothelial dysfunction, coronary artery calcification and inflammation, well-known cardiovascular risk factors in haemodialysis (HD) patients. In this study, we aimed to investigate the correlation of coronary artery calcification scores (CACS) with CFR in HD patients. METHODS Sixty-four end-stage renal failure patients were enrolled in this study (38 males, 26 females). Thirty-nine healthy subjects (22 males, 17 females) were included in the control group. Biochemical parameters and acute-phase inflammation marker [high-sensitivity C-reactive protein (hs-CRP)] of patients were recorded before dialysis. The CACS were measured by electron beam computerized tomography method. CFR recordings were performed by trans-thoracic Doppler echocardiography. The relationship between CACS and CFR was evaluated. RESULTS The mean CACS was 281 +/- 589 and 29 patients had CACS < 10. Patients with CACS > 10 had significantly lower CFR values compared to patients with CACS < 10 (1.56 +/- 0.38 vs 1.84 +/- 0.53, P = 0.024). However, there was no difference in hs-CRP values between the groups. CFR was negatively correlated with CACS (r = -0.276, P = 0.030). In multiple stepwise regression analysis, CACS was found to be an independent variable for predicting CFR (P = 0.048). During a follow-up of 18 months, 10 patients had experience of cardiovascular events. Patients with CACS > 10 had significantly higher event rate [34.5% (10/29) vs 0% (0/24)] compared to those with CACS < 10 (P = 0.001). Patients who developed cardiovascular events had significantly higher mean CACS and lower CFR values than the remaining group (P = 0.019 and P = 0.039). All of four patients who died during follow-up were in the CFR < 2 and CACS > 10 groups. CONCLUSIONS CACS was associated with CFR in HD patients. However, we did not find any association of inflammation with CACS and CFR. This association between CFR and CACS might indicate two different (anatomical and functional) aspects of the common pathophysiology of the arterial system in HD patients.

Association between chronic hepatitis C infection and coronary flow reserve in dialysis patients with failed renal allografts.

BACKGROUND Hepatitis C infection occurs frequently among patients with end-stage renal disease and increases the risk of atherosclerotic cardiovascular diseases. Endothelial dysfunction (ED) is an early event in the pathogenesis of atherosclerosis. It has been reported among patients treated with hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. The aim of the present study was to evaluate effects of chronic hepatitis C infection on ED in patients with failed renal transplants. METHODS Twenty-six nondiabetic, anti-hepatitis C virus (HCV)-positive (15 females, mean age: 38 +/- 8 years) and 26 anti-HCV-negative patients (15 females, mean age: 36 +/- 5 years), all of whom had returned to PD or HD after renal transplant failure were studied to assess coronary flow reserve (CFR) by transthoracic Doppler echocardiography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured as markers of chronic inflammation. CFR recordings and intima-media thickness measurements were performed using the Vivid 7 echocardiography device. RESULTS Demographic and clinical characteristics of patients were similar between the two groups. Serum hs-CRP levels were significantly higher among HCV-positive patients versus HCV-negative counterparts. HCV-positive patients showed lower CFR measurement than HCV-negative ones. Also, a negative correlation was observed between serum hs-CRP levels and CFR values. CONCLUSION CFR values are worse among anti-HCV-positive patients with failed renal transplants compared with anti-HCV-negative subjects. Graft dysfunction per se may aggravate a proinflammatory states thereby inducing ED. Furthermore, the presence of HCV is a greater trigger of ED among patients with renal failed grafts.

Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants.

OBJECTIVE The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation. METHODS Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed. RESULTS There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group. CONCLUSIONS Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.

Plasma Ghrelin Levels Are Associated with Coronary Microvascular and Endothelial Dysfunction in Peritoneal Dialysis Patients

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 ± 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and ≥ 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 ± 82.1 pg/mL) in patients with CFR ≥ 2 were significantly higher than those in patients with CFR< 2 (63.3 ± 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 ± 37.81 ng/mL vs. 63.95 ± 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C

BackgroundPatients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection.MethodsSixty patients (27 male, 33 female, mean age 50 ±15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-α and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight.ResultsSerum prohepcidin levels of HCV positive patients (135 ± 25 ng/mL) were significantly lower than HCV negative patients [148 ± 18 ng/mL, (p = 0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p = 0.016). Serum prohepcidin levels were positively correlated with ferritin (r = 0.405, p = 0.001) and IL-6 (r = 0.271, p = 0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r = 0.514 p = 0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r = 0.418, p = 0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r = 0.28, p = 0.008).ConclusionsHCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients.

Comparison of nutritional status in hemodialysis patients with and without failed renal allografts.

Yelken MB, Gorgulu N, Caliskan Y, Yazici H, Turkmen A, Yildiz A, Sever MS. Comparison of nutritional status in hemodialysis patients with and without failed renal allografts
Clin Transplant 2010: 24: 481–487.
© 2009 John Wiley & Sons A/S.

Endothelial dysfunction in hemodialysis patients with failed renal transplants

Gorgulu N, Yelken B, Caliskan Y, Elitok A, Cimen AO, Yazici H, Oflaz H, Golcuk E, Ekmekci A, Turkmen A, Yildiz A, Sever MS. Endothelial dysfunction in hemodialysis patients with failed renal transplants.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01160.x
© 2009 John Wiley & Sons A/S.

Effects of arteriovenous fistula on clinical, laboratory and echocardiographic findings in renal allograft recipients

PURPOSE Left ventricular hypertrophy (LVH) is frequently observed in patients with end-stage renal disease and renal allograft recipients, and is an independent and strong predictor of morbidity and mortality. Presence of a patent arteriovenous fistula (AVF) after renal transplantation may contribute to the persistent LVH. We investigated the clinical, laboratory, and echocardiographic findings in patients with renal transplants with or without AVF. METHODS A total of 130 renal transplant recipients were included in this study: 60 hemodialysis patients whose fistulas were still functional, 49 hemodialysis patients whose fistulas were spontaneous stopped or closed, and 21 peritoneal dialysis patients who had never had fistulas created. Laboratory parameters were measured and echocardiographic measurements were performed. RESULTS There were no significant differences regarding smoking status, blood pressures, or NT-proBNP, hs-CRP, iPTH, and TSH levels between the study groups. Left atrial, right atrial diameters, left ventricle end-diastolic diameter, left ventricle end-systolic diameter, interventricular septum thickness (IVST), left ventricle mass index (LVMI), pulmonary artery pressure (PAP), and ejection fraction were similar in the three groups. In correlation analysis, PAP was significantly correlated with serum uric acid and NT-proBNP levels. Also, there were positive and moderate correlations between the serum uric acid and the IVST. CONCLUSION Patent AVFs have not affected cardiovascular abnormalities such as LVH and LV mass index in patients with renal transplant. Hyperuricemia may be associated with increased PAP and high LVMI.

Serum uric acid level is associated with cardiac hypertrophy in renal transplant recipients

Caliskan Y, Gorgulu N, Yelken B, Akturk F, Yazici H, Turkmen A, Sever MS. Serum uric acid level is associated with cardiac hypertrophy in renal transplant recipients.
Clin Transplant 2011: 25: 368–374.