Murat Duranay

Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress POTENTIAL ROLE IN FRUCTOSE-DEPENDENT AND -INDEPENDENT FATTY LIVER

Background: Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. Results: Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. Conclusion: Rather than a consequence, uric acid induces fatty liver Significance: Hyperuricemic people are more prone to develop fructose-induced fatty liver. Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.

A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

BACKGROUND AND OBJECTIVES Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months. RESULTS Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = -0.55) and after (beta = -0.40) treatment. CONCLUSIONS Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.

Fibroblast Growth Factor 23 and Fetuin A are Independent Predictors for the Coronary Artery Disease Extent in Mild Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Cardiovascular disease in chronic kidney disease (CKD) is explained in part by traditional cardiovascular risk factors; by uremia-specific factors; and by abnormalities of mineral metabolism, factors involved in its regulation, and in the vascular calcification process. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In an unselected population of 177 patients with calculated GFR (eGFR) between 90 and 30 ml/min per 1.73 m(2), the link between the mineral metabolism abnormalities (calcium, phosphorus, calcium-phosphorus product), regulatory factors (parathyroid hormone [PTH], intact PTH [iPTH], vitamin D, fibroblast growth factor 23 [FGF 23], and fetuin A), and the severity of coronary artery disease (CAD) assessed by coronary angiography were evaluated in three subgroups defined by tertiles of Gensini lesion severity score. RESULTS The mean serum values for FGF 23 in the entire study population was 28.1 ± 17.3 RU/ml and for fetuin A was 473.1 ± 156.2 μg/ml. Patients with eGFR < 60 ml/min per 1.73 m(2) had significantly higher values of FGF 23 compared with patients with eGFR > 60 ml/min per 1.73 m(2). The Gensini score values significantly correlated with gender; arterial hypertension; and HDL cholesterol, eGFR, iPTH, FGF 23, and fetuin A levels. After the adjustments for traditional and uremia-related cardiovascular risk factors, the FGF 23 and fetuin A remained significant predictors of the Gensini score. CONCLUSIONS This study suggests that in a relatively young population with mild-to-moderate alteration of kidney function and with less traditional cardiovascular risk factors, anomalies of the serum FGF 23 and fetuin A levels appear early in the course of disease and are independent major predictors for extent of CAD.

Infectious complications after mass disasters: the Marmara earthquake experience.

The Marmara earthquake occurred on 17 August 1999. There were 639 renal victims, of whom 477 needed some form of renal replacement therapy. Although several medical complications have been reported in the literature, there has been no detailed description of infectious complications in patients with crush syndrome after earthquakes. Data from 35 hospitals considering clinical and laboratory findings, as well as infectious complications and the results of microbiological examinations, were analysed. 223 out of 639 (34.9%) patients had infectious complications, which comprised the most frequent medical problem in the renal victims. The patients who suffered from infections had a higher mortality rate than those who did not (p=0.03). Sepsis and wound infection were the main presentation of the infectious complications. 121 (18.9%) patients suffered from sepsis; the mortality rate was higher in these patients (27.3%) than in victims who did not suffer from sepsis (12.4%, p<0.0001). In a multivariate model, sepsis was associated with increased mortality (p=0.0002, odds ratio 2.45, 95% confidence interval 1.52–3.96). 53 (8.2%) and 41 (6.4%) patients had wound and pulmonary infections, respectively. Most of the infections were nosocomial in origin and caused by Gram-negative aerobic bacteria and Staphylococcus spp. Infectious complications are common in renal victims of catastrophic earthquakes and are associated with increased mortality when complicated by sepsis.

Comparison of effects of darbepoetin alfa and epoetin alfa on serum endothelin level and blood pressure.

It is well known that epoetin alfa increases serum endothelin (ET)-1 and blood pressure. No data are available, however, on the effects of darbepoetin alfa on serum ET-1 and blood pressure. This study was conducted to compare the effects of darbepoetin alfa and epoetin alfa on serum ET-1 and blood pressure in patients on hemodialysis (HD). A total of 42 patients on HD were included in the study. Serum samples for measuring levels of ET-1 were taken 30 min after administration of epoetin alfa. After blood samples had been taken from all patients, epoetin alfa was changed to darbepoetin alfa. Three months after the start of darbepoetin alfa treatment, blood samples were taken to measure the same parameters. Mean arterial blood pressure was measured before recombinant human erythropoietin (EPO) administration and 30 min after EPO administration while patients were taking epoetin alfa or darbepoetin alfa. Injection of epoetin alfa or darbepoetin alfa significantly increased serum ET-1 levels compared with levels in those patients who were not on EPO therapy (P < .05). When the effects of epoetin alfa on serum ET-1 level were compared with those of darbepoetin alfa, the 2 types of EPO were found to increase serum ET-1 levels similarly (P > .05). Administration of epoetin alfa or darbepoetin alfa increased systolic and diastolic blood pressures significantly over values in the control group (P < .05). Serum systolic and diastolic blood pressures increased similarly after injection of epoetin alfa or darbepoetin alfa. Administration of darbepoetin alfa increased blood pressure in patients on HD in a way that was positively correlated with enhanced ET-1 release; a similar correlation was noted with epoetin alfa.

Nebivolol improves renal function in patients who underwent angioplasty due to renal artery stenosis: a pilot study.

Renal artery stenosis (RAS) is a progressive disease and may lead to chronic kidney disease by deterioration of renal functions. Endothelial dysfunction is an important causative factor for kidney damage after RAS revascularization. Nebivolol, a new generation beta blocker induces endothelium-related arterial relaxation by nitric oxide (NO) and may improve endothelial dysfunction. This pilot study tested the effect of nebivolol on the glomerular filtration rate (GFR) in a series of 33 patients with severe RAS (>70%) who underwent revascularization. After revascularization, nebivolol was added to antihypertensive treatment in 17 randomly selected patients while 16 patients (control group) continued their standard treatment. Estimated glomerular filtration rate (eGFR), proteinuria as well as nitrite and nitrate levels were measured at baseline and 6 months after the revascularization procedure. Six months after revascularization, eGFR increased from 44.8 to 50.6 ml/min in the nebivolol group. In contrast, eGFR did not change in the control group. Nitrite/nitrate levels decreased to a significant extent both in the nebivolol and in the control group. Proteinuria decreased more in the nebivolol group compared to the control group. These pilot data support a full-fledged clinical trial, testing whether nebivolol may be beneficial in the post-revascularization phase in patients with RAS.

Additive Effectiveness of Everolimus Plus Tamoxifen Therapy in Treatment of Encapsulating Peritoneal Sclerosis

Peritoneal dialysis (PD) is one of the commonly used choices of continuous renal replacement therapies. Peritoneal membrane is damaged by using solutions with lower biocompatibility, peritonitis episodes, and vintage of PD therapy. Encapsulating peritoneal sclerosis (EPS) is a rare complication of PD and is presented by progressive fibrosis of the peritoneum. Fibrous tissue entrapment of the intestine, leading to complete intestinal obstruction, is referred to as EPS, the most severe form of sclerosing peritonitis. EPS is irreversible fibrosis of the peritoneal membrane usually associated with high rates of morbidity and mortality. Preventive strategies are the best choice of treatment. Also there is no proven effective therapy for EPS; there are only small-sized trials. Herein we present a case of EPS who improved with everolimus plus tamoxifen therapy.

Brucella glomerulonephritis: case report and review of the literature.

The authors present the case of a 17-year-old shepherd who was diagnosed with diffuse proliferative glomerulonephritis and diffuse tubulointerstitial nephritis during the course of Brucella infection. The pathogenesis and the mechanism of renal involvement in brucellosis is discussed in light of the pertinent literature.

Is Conventional Hemodialysis Enough to Manage Carbamazepine Intoxication

Hemodialysis (HD) is a technique that helps in the management of drug intoxications/overdoses – the most important point being the protein-binding rate of the molecules which have to be cleared. In cases where the drug is not bound to the proteins, conventional HD may be effective enough, but if the drug is highly bound to proteins then HD may be insufficient to be effective. Hemoperfusion and albumin dialysis are therefore appropriate alternatives. Herein we report a case of carbamazepine intoxication where conventional HD treatment was performed.

Comparison of incidence of peritonitis between peritoneal dialysis solution types

Background: Peritonitis is an important cause of morbidity and mortality in patients receiving peritoneal dialysis (PD). However, there are no data about the comparison of the incidence of peritonitis among PD solution types. The aim of the present study was to compare the incidence of peritonitis among PD solutions in PD patients treated either with Nutrineal or with Extraneal or with conventional glucose solutions. Materials and Methods: A total of 147 patients (60 female and 87 male) who underwent PD were included in the study. Of these patients, 47 used only glucose solutions (group I), 79 used glucose solutions combined with Extraneal (group II) and 21 used glucose solutions combined with Nutrineal (group III). The laboratory values and demographics of the patients were noted. Results: There was no significant difference in the frequency of peritonitis among the three groups. Peritonitis occurred in 14 of 47 patients (29.8%) in group I, in 28 of 79 patients (35.4%) in group II and in 6 of 21 patients (28.6%) in group III. Patients with serum albumin levels below 3 g/dl had a significantly higher peritonitis rate than patients with serum albumin levels above 3 g/dl (p < 0.05). Conclusion: We have shown that a low serum albumin level is an important risk factor for the development of peritonitis in CAPD patients. The PD solution does not appear to be a risk factor for the development of peritonitis in CAPD patients, although this question should be studied further with larger numbers.