Ismail Kocyigit

Role of Grape Seed Extract on Methotrexate Induced Oxidative Stress in Rat Liver

UNLABELLED The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by its severe hepatotoxicity. Regarding the mechanisms of these adverse effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether grape seed extract (GSE), a new natural free radical scavenger, could ameliorate the MTX-induced oxidative injury in the rat liver. The animals were divided into 3 groups. Each group consisted of 12 animals. MTX-GSE group: rats were given GSE (100mg/kg body weight) orally for 15 days, and a single dose of MTX (20 mg/kg, intraperitoneally) was added on the 10th day. MTX group: these received placebo distilled water (orally) instead of GSE for 15 days and the same MTX protocol applied to this group on the 10th day. CONTROL GROUP rats were given distilled water (orally) through 15 days and physiological saline (intraperitoneally) instead of MTX was administered on the 10th day in a similar manner. On the 16th day, liver tissue samples were obtained under deep anaesthesia. The level of malondialdehyde (MDA), an end product of lipid peroxidation, and the activities of süperoxide dismutase (SOD) and catalase (CAT), two important endogenous antioxidants, were evaluated in the tissue homogenates. MTX administration increased the MDA level and decreased the SOD and CAT activities in the liver homogenates (p < 0.001), while these alterations were significantly reversed by GSE treatment (p < 0.001). MTX led to significantly reduced whole blood count parameters (p < 0.05). When GSE was supplemented, no significant changes in blood count parameters were noted. It appears that GSE protects the rat liver and inhibits methotrexate-induced oxidative stress. These data indicate that GSE may be of therapeutic benefit when used with MTX.

Therapeutic plasma exchange in patients with neurologic diseases: Retrospective multicenter study

Therapeutic plasma exchange (TPE) is commonly used in many neurological disorders where an immune etiology was known or suspected. We report our experience with TPE performed for neuroimmunologic disorders at four university hospitals. The study was a retrospective review of the medical records of neurological patients (n=57) consecutively treated with TPE between April 2006 and May 2007. TPE indications in neurological diseases included Guillain-Barrè Syndrome (GBS) (n=41), myasthenia gravis (MG) (n=11), acute disseminated encephalomyelitis (ADEM) (n=3), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=1) and multiple sclerosis (MS) (n=1). Patient median age was 49; there was a predominance of males. Twenty-two patients had a history of other therapy including intravenous immunoglobulin (IVIG), steroid, azothioprin, and pridostigmine prior to TPE. Another 35 patients had not received any treatment prior to TPE. All patients were classified according to the Hughes functional grading scores pre- and first day post-TPE for early clinical evaluation of patients. The TPE was carried out 1-1.5 times at the predicted plasma volume every other day. Two hundred and ninety-four procedures were performed on 57 patients. The median number of TPE sessions per patient was five, and the median processed plasma volume was 3075mL for each cycle. Although the pre-TPE median Hughes score of all patients was 4, it had decreased to grade 1 after TPE. While the pre-TPE median Hughes score for GBS and MG patients was 4, post-TPE scores were decreased to grade 1. Additionally, there was a statistically significant difference between post-TPE Hughes score for GBS patients with TPE as front line therapy and patients receiving IVIG as front line therapy (1 vs. 3.5; p=0.034). Although there was no post-TPE improvement in Hughes scores in patients with ADEM and CIDP, patients with MS had an improved Hughes score from 4 to 1. Mild and manageable complications such as hypotension and hypocalcemia were also observed. TPE may be preferable for controlling symptoms of neuroimmunological disorders in early stage of the disease, especially with GBS.

The long‐term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients

The aim of this prospective study was to evaluate long‐term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end‐stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long‐term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long‐term period.

Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients.

Background/Aims: Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. Methods: Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. Results: Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. Conclusion: Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.

Role of neutrophil/lymphocyte ratio in prediction of disease progression in patients with stage–4 chronic kidney disease

BACKGROUND Chronic kidney disease (CKD) tends to progress to end-stage renal disease without any intervention. Neutrophil/lymphocyte (N/L) ratio may be indicative of an underlying inflammatory state. We aimed to investigate the role of N/L ratio for prediction of progression to dialysis in patients with stage 4 CKD. METHODS We included 105 patients with stage 4 CKD in the study. All patients were followed up from the first admission to dialysis. N/L ratio was measured during follow-up. Patients were divided into two groups as baseline N/L (N/Lb) ratio < 3 and N/Lb ratio =3 and rapid progression was defined as > 5 mL/minute/year loss of creatinine clearance and slow progression as < 5 mL/minute/year. RESULTS Patients with N/L ratio =3 demonstrated high progression rate compared to patients who had N/L ratio <3 (2.6 ± 1.6 and 5.4 ± 3.3, P<.001). hs-CRP levels were higher in patients who had rapid progression (5.6 ± 3.0 and 20.2 ± 10.6, P<.001). The sensitivity and specificity of N/Lb were 79% and 69%, respectively, when the cutoff level was accepted as N/L ratio =3 for determining rapid progression. Furthermore, patients with a high N/Lb ratio had worse prognosis and significantly faster progression to the dialysis compared with those with a low N/L ratio. CONCLUSION Our results suggest that N/L ratio may predict the progression rate of stage 4 chronic kidney disease to dialysis. It is an easily accessible and useful marker for monitoring CKD patients in clinical practice.

A Link between the Intrarenal Renin Angiotensin System and Hypertension in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Early onset of hypertension and its consequences account for the great majority of deaths in patients with autosomal dominant polycystic kidney disease (ADPKD). Renin-angiotensin system (RAS) components have been shown in ADPKD kidneys independent of systemic RAS. Thus, we examined the urinary angiotensinogen (UAGT) levels as a biomarker of intrarenal RAS status in ADPKD patients with/without hypertension and healthy subjects. Methods: Eighty-four ADPKD patients (43 with hypertension and 41 without hypertension) and 40 healthy controls were studied cross-sectionally. Patients with glomerular filtration rate <60 ml/min were excluded from the study. Hypertension was diagnosed with ambulatory blood pressure monitoring. Urinary and plasma concentration of angiotensinogen, spot urine microprotein and creatinine (UCre) levels were recorded for each participant. Results: UAGT/UCre levels were higher in hypertensive ADPKD patients (23.7 ± 8.4) compared with normotensive ADPKD patients (16.6 ± 5.2) and healthy controls (6.9 ± 3.3; p < 0.001). In univariate analysis, UAGT correlated with systolic blood pressure, diastolic blood pressure (DBP) and proteinuria. The independence of these correlations was analyzed in a regression model, and UAGT was shown to be significantly predicted by proteinuria and DBP. Conclusion: Intrarenal RAS activation which is monitored by UAGT levels clinically may be a harbinger of hypertension and kidney disease in ADPKD patients.

Carotid‐jugular arteriovenous fistula and cerebrovascular infarct: A case report of an iatrogenic complication following internal jugular vein catheterization

Central venous catheterization is frequently performed for perioperative management and long‐term intravenous access. Although complications associated with central venous catheter insertion have been widely reported, there are few reports of carotid‐jugular arteriovenous fistula formation. Endovascular procedures are associated with a risk of immediate and delayed thromboembolic and ischemic complications. We describe a case of a carotid‐jugular arteriovenous fistula and a cerebrovascular infarct following the insertion of a double‐lumen catheter for hemodialysis access. We provide recommendations for the prevention and the early detection of this iatrogenic complication.

Serum Uric Acid Levels and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit endothelial dysfunction (ED) despite normal levels of renal function. Hyperuricemia occurs in these patients and has been postulated to affect ED through the generation of oxidative stress. We therefore investigated the prevalence of ED and its association with serum uric acid levels in early-stage ADPKD. Methods: A cross-sectional design was used for the assessment of prevalent patients with early-stage (normal renal function) ADPKD (n = 91) from two academic medical centers. ED was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Serum uric acid levels were evaluated using an Olympus AU2700 autoanalyzer. Results: ADPKD patients with higher serum uric acid levels had a higher asymmetric dimethylarginine (ADMA) level (1.19 ± 0.2 vs. 1.47 ± 0.3, p < 0.001) and lower FMD rates (8.1 ± 1.3 vs. 6.8 ± 0.7, p < 0.001). In multiple regression analysis for predictors of cohort FMD, uric acid (β = -0.32, p < 0.001), ADMA (β = -0.36, p < 0.001), high-sensitivity C reactive protein (CRP; β = -0.32, p < 0.001) and estimated glomerular filtration rate (eGFR; β = 0.33, p < 0.001) all predicted FMD. Conclusions: In early-stage ADPKD patients, uric acid levels, serum ADMA and eGFR all independently predict ED in a similar manner. Future studies are needed to investigate the causes of elevated serum uric acid, ADMA and CRP in these patients.

Protective effect of N-acetylcysteine from drug-induced ototoxicity in uraemic patients with CAPD peritonitis

AIM Peritonitis is currently one of the leading complications of continuous ambulatory peritoneal dialysis (CAPD) treatment. Aminoglycosides and vancomycin are used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. N-acetylcysteine (NAC) is a molecule used in the treatment and prophylaxis of many diseases related to oxidative stress. The aim of this study was to examine whether ototoxicity due to antibiotics used in the treatment of CAPD peritonitis can be prevented by NAC. METHODS Sixty patients, who first developed CAPD peritonitis attacks from February 2008 to April 2010 were included in this study. Patients were divided into two groups, those taking an additional NAC treatment (n = 30) and a control group (n = 30). Low- and high-frequency hearing function tests were performed on the two groups before treatment (baseline), at the end of the first (early follow-up) and the fourth week after the treatment (late follow-up). Total doses of vancomycin and amikacin were recorded. RESULTS There was no statistically significant difference between the groups in terms of hearing functions at the beginning. However, patients taking NAC had better hearing function test results 4 weeks after the treatment compared with those of the control group (P < 0.05). There were no statistical differences between posttreatment low-frequency hearing function tests conducted at the baseline and the first and the fourth weeks in patients taking NAC. The first and the fourth weeks low-frequency hearing functions worsened when compared with the baseline low-frequency results in the control group (P < 0.001). It was found that NAC had a protective effect against ototoxicity on low-frequency (0.25-8 KHz) hearing functions. The first and the fourth weeks high-frequency hearing functions improved when compared with baseline high-frequency hearing functions in patients taking NAC (P < 0.05), while they worsened. The first and fourth weeks high-frequency tests worsened when compared with the baseline high-frequency tests in the control group (P < 0.001). CONCLUSIONS The present study suggests that intraperitoneal aminoglycoside and vancomycin administration in CAPD patients may cause low- and high-frequency hearing loss, and this ototoxic effect is related to the dose given. It was found that when the antioxidant NAC is administered alone, it prevents ototoxicity, associated with intraperitoneal amikacin and vancomycin in patients with CAPD peritonitis. In addition, it was revealed that NAC may also have a curative effect on impaired high-frequency hearing functions.

Loss of Bone Mineral Density in Renal Transplantation Recipients

AIM This study investigated the prevalence and contributing factors of loss of bone mineral density after renal transplantation among Turkish patients. PATIENTS AND METHODS The study included 70 subjects, namely 50 males and 20 females of overall mean age of 36.94 ± 10.09 years. We measured femoral neck mineral density by dual-energy X-ray absorptiometry (DEXA). A T score above -1 was defined as a normal bone mineral density compared with T scores of -1.0 to -2.5 or below -2.5 which were defined as either osteopenia or osteoporosis, respectively. RESULTS At a median duration of 23 months after renal transplantation, osteopenia or osteoporosis was observed among 30 (42.9%) or 30 (42.9%) of the 70 patients, respectively. The mean body mass index (BMI) value was significantly higher among the normal than the osteoporotic group: 27.59 ± 4.66 kg/m(2) vs 24.18 ± 3.57 kg/m(2), respectively. However, no significant differences occurred in terms of BMI among the other groups. The amount of proteinuria was significantly lower in the normal than the osteopenic or osteoporotic group: (12.5 (range, 10.0-20.0); 105.0 (10.0-2800.0) or 215.5 (10.0-1880.0) mg/d (P = .001 and .004, respectively). In contrast, there was no significant difference between the amounts of proteinuria displayed by the osteopenic group and the osteoporotic group (P < .05)]. These patient groups showed no difference in age, gender, donor source, cause of end-stage renal disease (ESRD), pretransplant dialysis modality, duration of dialysis, use of a vitamin D preparation, immunosuppressive regimen, posttransplantation period, levels of iPTH or 25 hydroxy vitamin D3 (25OH vit D), exposure to tacrolimus or cyclosporine (CyA), calcium × phosphate product, serum albumin and hemoglobin content, creatinine clearance, or serum bicarbonate concentrations (P > .05). The T scores of the femoral neck correlated with BMI (r: 0.415; P = .001), 25OH vit D level (r: 0.268, P = .026), creatinine clearance (r: 0.273, P = .022), and serum glucose level (r: 0.349, P = .003). It inversely correlated with the amount of proteinuria (r: -0.263, P = .028), serum alkaline phosphatase level (r: -0.329, P = .005), and serum magnesium concentration (r: -0.252, P = .035). Upon multivariate analysis, BMI and 25OH vit D level were observed to be independent risk factors for loss of femoral mineral density. CONCLUSION Loss of bone mineral density is a common complication that correlates with low BMI values and decreased 25OH vit D levels as major risk factors for this problem.