Atila Altuntas

Malnutrition-inflammation score and endothelial dysfunction in hemodialysis patients.

OBJECTIVE The aim of this study was to find out the relationship between Malnutrition-Inflammation score (MIS) and the endothelial function parameters, including measurements of flow-mediated vasodilatation (FMD) in the brachial artery and serum vascular cell adhesion molecule-1 (VCAM-1). Furthermore, predictors of FMD were also assessed. MATERIALS AND METHODS A total of 70 anuric hemodialysis patients were enrolled in this cross-sectional study. Measurements of FMD, serum VCAM-1, oxidized low density lipoprotein cholesterol (oxLDL) were done before the mid-week dialysis session from all participants at the time of MIS calculation. Patients were divided into 3 groups according to MIS (the MIS was ≤4 in group I, 4< and ≤7 in group II, and >7 in group III) and compared for above parameters. RESULTS Patients with higher MIS had higher serum high sensitive C-reactive protein, oxLDL and VCAM-1 levels whereas these patients had lower serum albumin, hemoglobin levels, and FMD rates. MIS was positively correlated with high sensitive C-reactive protein, oxLDL and VCAM-1 levels. However, there was a negative correlation between MIS and FMD. MIS and oxLDL were found as an independent significant predictors of FMD (P = .014 and P = .018, respectively) in a multivariate analysis. CONCLUSIONS MIS is a useful tool in prediction of the severity of endothelial dysfunction. Furthermore, decrease in MIS by the modifiable parameters and also treatment of oxLDL could be expected to improve endothelial dysfunction in hemodialysis patients.

Effect of cholecalciferol replacement on vascular calcification and left ventricular mass index in dialysis patients

Abstract Objective: The aim of this study was to determine the effect of oral cholecalciferol treatment on vascular calcification, left ventricular mass index (LVMI) and other cardiac functions in dialysis patients. Design and methods: A six-month course of oral cholecalciferol treatment was recommended to dialysis patients with vitamin D insufficiency. While 26 patients were given cholecalciferol treatment, 17 patients who could not tolerate to therapy received standard therapy. Initial biochemical parameters were measured, and they were measured again after 6 months of treatment. Echocardiographic measurements were also performed, and the vascular calcification score (VCS) was calculated at baseline and at the 6th month. Results: The cholecalciferol replacement group showed no significant change in LVMI and VCS values (p > 0.05). However, while LVMI was similar between groups at initial evaluation, it was lower in the cholecalciferol group at the 6th month when compared to the standard treatment group (141.8 ± 40.2 g/m2 vs. 166.3 ± 31.4 g/m2; p = 0.04). Likewise, left ventricular diastolic diameters (48.8 ± 5.1 mm vs. 47.5 ± 4.6 mm; p = 0.023) and left atrial diameters (41.2 ± 8.9 mm vs. 38.9 ± 8.1 mm; p = 0.006) decreased in the cholecalciferol group. Additionally, significant increases were observed in serum 25-hydroxyvitamin D (25(OH)D) and albumin levels, with a significant decrease in serum C-reactive protein levels. Conclusion: A lesser increase in left ventricular mass and better diastolic functions was observed in dialysis patients after 6 months of cholecalciferol treatment.

Caffeic acid phenethyl ester protects against amphotericin B induced nephrotoxicity in rat model.

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 μmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 μmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models.

Manganese superoxide dismutase, glutathione peroxidase and catalase gene polymorphisms and clinical outcomes in acute kidney injury

Abstract Introduction The aim of this study was to evaluate the potential association of single gene polymorphisms of manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1) and catalase (CAT) with clinical outcomes of acute kidney injury (AKI). Materials and methods Ninety AKI patients and 101 healthy volunteers were included in the study. Determination of MnSOD rs4880, GPX1 rs1050450 and CAT rs769217 polymorphisms was performed using real-time polymerase chain reaction amplification. The duration of hospitalization of AKI patients, dialysis and intensive care requirements, sepsis, oliguria and in-hospital mortality rates were assessed. Results The MnSOD, GPX1 and CAT genotypes and allele frequencies of AKI patients did not differ significantly from those of healthy controls. In patients with a T allele in the ninth exon of the CAT gene, intensive care requirements were greater than those of patients with the CC genotype (p = 0.04). In addition, sepsis and in-hospital mortality were observed significantly more frequently in patients with a T allele in the ninth exon of the CAT gene (p = 0.03). Logistic regression analysis determined that bearing a T allele was the primary determinant of intensive care requirements and in-hospital mortality, independent of patient age, gender, presence of diabetes and dialysis requirements (OR 6.10, 95% CI 1.34–27.81, p = 0.02 and OR 10.25, 95% CI 1.13–92.80, p = 0.04, respectively). Conclusion Among AKI patients in the Turkish population, hospital morbidity and mortality were found to be more frequent in patients bearing a T allele of the rs769217 polymorphism of the CAT gene.

Protective Effects of Caffeic Acid Phenethyl Ester on Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

We investigated the protective effect of caffeic acid phenethyl ester (CAPE) on cyclophosphamide‐induced hemorrhagic cystitis in rats in comparison with 2‐mercaptoethane sulfonate (MESNA). Forty male rats were randomized into four groups: group 1 (control), group 2 (cyclophosphamide), group 3 (cyclophosphamide + MESNA), group 4 (cyclophosphamide + CAPE). Cyclophosphamide injection increased malondialdehyde levels indicating oxidative stress, whereas CAPE and MESNA ameliorated malondialdehyde levels in the bladder (p < 0.05). Only catalase activities were decreased significantly in both groups (cyclophosphamide + MESNA and cyclophosphamide + CAPE, p < 0.05). Pretreatment with CAPE (p < 0.01) resulted in a significant decrease in nitric oxide levels when compared with the cyclophosphamide group. When we consider the studies that show the critical importance of increased nitric oxide levels in pathogenesis of cyclophosphamide‐induced hemorrhagic cystitis, we suggest that it would be more beneficial to use MESNA with CAPE to prevent histological damage.

Telomerase activity in patients with stage 2–5D chronic kidney disease☆

BACKGROUND Molecular mechanisms of increased cardiovascular mortality in chronic kidney disease (CKD) associated with biological age are not well understood. Recent studies support the hypothesis that common factors responsible for this phenomenon are cellular aging and telomere dysfunction. OBJECTIVES The purpose of this study was to investigate the relation between telomerase activity and CKD stages. METHODS The study included 120 patients who were followed-up for CKD stage 2-5D, composed of 30 patients of each stage and 30 healthy volunteers without any known disease who were admitted to our hospital for routine check-ups. Telomerase activity in peripheral blood mononuclear cells (PBMC) was measured using the TRAP assay. RESULTS A significant difference was observed for telomerase activity in PBMC between groups. The detected levels were lowest in the healthy control group (0.15±0.02), and highest in CKD stage 5D patients (0.23±0.04). In CKD patients, telomerase activity in PBMC was positively correlated with the CKD stage, serum creatinine, potassium and parathormone levels, and negatively correlated with estimated glomerular filtration rate (eGFR), body mass index (BMI), platelet count and serum calcium levels. According to the linear regression analysis, independent predictors for high telomerase activity in CKD patients were eGFR and BMI. CONCLUSION Telomerase activity in PBMC increases with advancing CKD stage in CKD patients. Increased telomerase activity in PBMC is associated with eGFR and BMI.

SP663THE RELATIONSHIP BETWEEN SERUM FETUIN A LEVELS AND FETUIN GENE POLYMORPHISM IN HEMODIALYSIS PATIENTS

Introduction: Fetuin A, also called Heramans Schmid alpha 2 glycoprotein (AHSG), is one of the important proteins that inhibit vascular calcification. In this study, we aimed to evaluate relationship between AHSG gene polymorphism and fetuin A levels. Materials and methods: 152 patients receiving regular hemodialysis treatment and 61 healthy controls were included to this cross-sectional study. Serum fetuin-A levels were assessed by ELISA method. Thr256Ser and Thr248Met gene polymorphisms are determined by PCR-RFLP. Results: Serum fetuin A level in hemodialysis patients (330.5 ± 171.2 mg/L) was significantly lower as compared to control group (382.9 ± 138.5 mg/L) (p=0.001). Significant negative correlation between fetuin-A and C-reactive protein (CRP) (r=-0.28, p<0.0001) was found. The distribution of Thr256Ser and Thr248Met gene polymorphisms in hemodialysis and control groups were similar. In hemodialysis group, serum fetiun A levels in the patients with genotype Thr/Thr (n=94, 366.9 ± 184.2 mg/L) were found to be singnificantly higher than in the patients with genotype Thr/Ser (n=52, 278.1 ± 132.7 mg/L) and Ser/Ser (n=6, 212.5 ± 63.3 mg/L) (respectively; p=0.005, p=0.022). Unlike Thr256Ser polymorphism, serum Fetuin-A levels did not differ between Thr248Met gene polymorphism genotypes. Conclusion: The current study showed that HD patients with altered polymorphism of the AHSG Thr256Ser gene appear to be a negative prognostic factor on serum Fetuin-A levels. In other words, it can be speculated that fetuin-A Thr256Ser gene polymorphism, particularly genotypes Thr/Ser and Ser/ Ser, may be an additional promoting risk factor for vascular ossification in HD patients.

AB0162 Protective Effects of Caffeic Acid Phenethyl Ester (CAPE) on Cyclophosphamide Induced Hemorrhagic Cystitis in Rats

Background Cyclophosphamide (CP) is commonly used chemotherapeutic agent in malignancies and rheumatic diseases. Hemorrhagic cystitis (HC) is a serious complication of CP treatment. CAPE, antioxidant and anti-inflammatory molecule, is a major component of honeybee propolis and structurally similar to flavonoids. Objectives We investigated the protective effect of Caffeic asit phenyl ester (CAPE) on cyclophosphamide (CP) induced hemorrhagic cystitis (HC) in rats in comparison with mesna Methods Forty male Wistar rat ages between 8-12 weeks were divided into four groups by random sampling method. HC induction was performed using an urotoxic dose of 100 mg/kg CP. Group 1 (Control) animals were injected with the same amount of saline and served as controls. Group 2 (CP) received only CP, group 3 (CP+mesna) received 100 mg/kg CP and mesna in dosage of 21,5 mg/kg which was given 20 minutes before, 4 and 8 hours after CP injection. Group 4 (CP+CAPE) received 100mg/kg CP and pretreated with CAPE (10 μmol/kg/day) at 48 and 24 hours and also 20 minutes before CP injection. All drugs were administered intraperitoneally. The bladder tissues were cut into two equal pieces from top to the bottom. One half was stored at -80°C for determination of SOD and CAT activities with MDA and NO concentration and the other half was fixed for 24 hr in 10% buffered formaldehyde for histological evaluation. Results Control animals had histologically normal bladders. CP caused severe microscopic mucosal injury in the bladder. Mesna exhibited significant histological protection against bladder damage of CP. CAPE had minimal protective effect on histological damage. CP injection which caused HC increased MDA levels indicating oxidative stres while CAPE and mesna ameliorated MDA levels in the bladder (p>0.05). SOD and CAT activities were decreased in the tissue samples of CP+mesna and CP+CAPE group. However, only CAT activities were decreased significantly in both groups (CP+mesna and CP+CAPE p<0.05). Pretreatment with CAPE (p<0.01) resulted in significant decrease in NO level when compared with CP group. Conclusions When we consider the studies which show the critical importance of increased NO levels in the pathogenesis of cyclophosphamide induced hemorrhagical cystitis, we suggest that it would be more benefical to use mesna with CAPE to prevent histological damage. References Korkmaz A, Oter S, Deveci S, Ozgurtas T, Topal T, Sadir S, Bilgic H. Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats. J Urol 2003;170:2498– 2502 Natarajan K, Singh S, Burke TR, Grunberger D, Aggrawal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996:20;93(17): 9090–9095. Disclosure of Interest None declared

Vaginal leakage of peritoneal dialysate in a peritoneal dialysis patient.

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