Investigation of doxorubicin combined with ciprofloxacin-induced cardiotoxicity: from molecular mechanism to fundamental heart function.

This study was designed to investigate the impacts of Doxo alone and in combination with Cipro on the hepatic and cardiac CYP1A2, CYP2J3, and CYP3A1 mRNA levels. We also aimed to analyze the cardiac function by perfusing isolated rat hearts. Rats were given Doxo and/or Cipro in chronic (3-week) and acute (single-day) dosing schedules. Cardiac CYP2J3, CYP3A1, and CYP1A2 gene expression levels were measured by quantitative reverse transcription PCR. Cardiac functions of the isolated hearts were evaluated by using the Langendorff technique. Doxo alone (2.5 mg/kg) and Doxo + Cipro (2.5 mg + 20 mg/kg) significantly decreased hepatic CYP1A2 expression compared to saline, whereas Doxo (2.5 mg/kg) and Doxo + Cipro (2.5 mg + 20 mg/kg) showed significantly higher cardiac CYP1A2 expression in comparison to control. In the liver tissue, Doxo (2.5 mg/kg) and Doxo + Cipro (2.5 + 20 mg/kg) decreased the CYP2J3 expression than the control group. The Doxo (2.5 mg/kg) and Doxo + Cipro (2.5 + 20 mg/kg)-treated group had significantly higher cardiac CYP2J3 expression compared to control. Doxo (2.5 mg/kg; cumulative dose 15 mg/kg) and Doxo + Cipro (2.5 + 20 mg/kg) showed significantly higher cardiac CYP3A1 expressions than the control. Rate-pressure product (HR × LVDP)/1000) showed an overall decrease in cardiac functions of Doxo (2.5 mg/kg) and Doxo + Cipro (2.5 + 20 mg/kg)-treated group. We found considerable effects in chronic protocol; Doxo alone high dose and plus Cipro decreased hepatic CYP1A2 and CYP2J3 mRNA. On the other hand, these treatment groups exhibited an increase in the cardiac CYP1A2, CYP2J3, and CYP3A1 expression and likewise deteriorated the overall hemodynamic parameters.

Dialyzing women and men: does it matter? An observational study.

BACKGROUND: Application and consequences of hemodialysis treatment may differ between genders; focusing on these differences may be useful to optimize outcomes. METHODS: Data from 1 999 648 hemodialysis sessions performed in 10 984 (3316 incident and 7668 prevalent) patients, treated in 55 centers of the European Clinical Database (EuCliD)-Turkey, were analyzed, and various demographic, clinical, biochemical, therapeutic and prognostic parameters were compared. RESULTS: There were 1905 male and 1411 female incident and 4339 male and 3329 female prevalent patients. For females, the mean age in incident (61.8 ± 14.9 years) and prevalent (58.3 ± 15.2 years) patients was higher than for males (60.2 ± 14.8 and 56.5 ± 14.9 years, respectively) (P < 0.001 for both analyses). Also, body mass index was higher, while the hemoglobin level, and the percentage of interdialytic weight gain and arteriovenous fistula were lower. Serum phosphorus was similar in both genders in incident cases, while it was lower in prevalent female patients. Serum parathyroid hormone levels were lower in incident, but higher in prevalent male cases. Erythropoiesis-stimulating agents and vitamin D preparations were more frequently used in female incident and prevalent patients. Hospitalization was more frequent in prevalent females, while it did not differ significantly in the incident cases. Overall, no significant difference was observed in survival rates at 3 years in both incident and prevalent male and female patients. CONCLUSIONS: Many parameters differ significantly between female and male dialysis patients. Considering the effects of sex on several parameters may be a valuable approach for achieving better outcomes when formulating treatment strategies in this patient population.

Naturally nonanemic dialysis patients: Who are they?

Introduction Not only anemia, but also erythropoiesis stimulating agent (ESA)s for treating anemia may adversely affect prognosis of chronic hemodialysis patients. Various features of naturally (with no ESA usage) nonanemic patients may be useful for defining several factors in the pathogenesis of anemia. Methods Data, retrieved from the European Clinical Database (EuCliD)-Turkey on naturally nonanemic prevalent chronic hemodialysis patients (n: 201) were compared with their anemic (those who required ESA treatment) counterparts (n: 3948). Findings Mean hemoglobin values were 13.5 ± 0.8 and 11.5 ± 0.9 g/dL in nonanemic and anemic patients, respectively (P < 0.001). Nonanemia status was associated with younger age, male gender, longer dialysis vintage, nondiabetic status, more frequent hepatitis-C virus seropositivity and more frequent arteriovenous fistula usage. Serum ferritin and CRP levels and urea reduction ratio were higher in ESA-requiring patients. One (99%) and two (95.3%) years survival rates of the "naturally nonanemic" patients were superior as compared to anemics (91.0% and 82.6%, respectively), (P < 0.001). Discussion "Naturally nonanemic" status is associated with better survival in prevalent chronic hemodialysis patients; underlying mechanisms in this favorable outcome should be investigated by randomized controlled trials including large number of patients.

Recurrent lupus nephritis after transplantation: Clinicopathological evaluation with protocol biopsies.

AIM: Lupus nephritis (LN) is an important complication of systemic lupus erythematosus (SLE). The aim is to use indication and protocol biopsies to determine clinicopathological findings and outcomes of patients with LN undergoing kidney transplantation (KTx). METHODS: Patients who underwent KTx due to LN were retrospectively analyzed. Recurrent LN (RLN) was diagnosed by transplant kidney biopsy. RESULTS: Among 955 KTx patients, 12 patients with LN as the cause of end-stage renal disease were enrolled. Five patients were male. Mean follow-up time was 63 ± 34 months. At the last follow-up visit, mean levels of serum creatinine and proteinuria were 137.0 ± 69.0 µmol/L and 0.26 ± 0.26 g/day, respectively. Eighteen indication and 22 protocol biopsies were performed; 27 biopsies were additionally evaluated by immunofluorescence. In two recipients, subclinical RLN was confirmed by protocol biopsies. Clinical recurrence occurred in four patients. Among patients with RLN, time from diagnosis of LN to KTx was significantly shorter and use of ATG as induction treatment was significantly lower. Graft loss occurred in two recipients who had clinical RLN. Five-year overall graft survival was 85.7%. CONCLUSION: Kidney transplantation is a reasonable option for patients with ESRD secondary to SLE. However, recurrence of LN is common if protocol biopsies are included in post-transplantation surveillance.

The relationship between renal volume and histology in obese and nonobese kidney donors.

BACKGROUND: Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. MATERIALS AND METHODS: Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. RESULTS: Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). CONCLUSIONS: In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival.

20 years since the establishment of the BANTAO association (Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs).

The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was born in Ohrid on October 9, 1993. The war in former Yugoslavia negatively affected the development of nephrology and also the connections among the nephrologists from the Balkans. However, there was willingness for further mutual collaboration between the nephrologists from the Balkans. The war in Yugoslavia created hate among people, between the newly established countries, and there were problems with the recognition of the names of the new countries, and so, the nephrologists decided to apply the ancient principle of using the names of the cities, instead of the countries, as the founders of the Association. The main goal of BANTAO is to promote scientific and technical cooperation in the fields of renal disease and artificial organs between the regions on the Balkan Peninsula and the world, to give an opportunity for exchange of experience and knowledge among the experts in the area and to engage in collaborative projects in order to demonstrate that cooperation is possible even on the turbulent Balkan Peninsula. The I BANTAO congress was held in Varna from September 22 to 24th, 1995 (President--D. Nenov, Varna). The II congress of BANTAO was held from September 6th to 10th, 1997 in Struga, (President--M. Polenakovic, Skopje). The III BANTAO congress was held in Belgrade from September 18th to 20th, 1998 (President--Lj. Djukanovic, Belgrade). The IV congress of BANTAO was held in Izmir from 14th to 16th November 1999 (President--A. Akcicek, Izmir). The V Congress of BANTAO was held in Thessaloniki from September 30th to October 3rd, 2001 (President--P. Stathakis, Athens). The VI Congress of BANTAO was held for the second time in Varna from 6th to 9th October 2003 (President--D. Nenov, Varna). The VII congress of BANTAO was held from September 8th to 11th, 2005 in Ohrid, (President--M. Polenakovic, Skopje). The VIII BANTAO congress was held in Belgrade, 16-19 September 2007 (President--V. Nesic, Belgrade). The IX BANTAO congress was held in Antalya, 18-22 November 2009 (President--A. Basci, Izmir). The X BANTAO congress was held from 13 to 15 October 2011 in Chalkidiki (President--D. Tsakiris, Thessaloniki). The XI BANTAO congress is being held on 26-29 September 2013 in Timisoara (President--A. Schiller, Timisoara). At the VII BANTAO Congress for the first time a CME Course was organized by ERA/EDTA and ISN/COMGAN entitled "Frontiers in Nephrology" with seven distinguished speakers. Very important event in the existence of BANTAO is the appearance of the BANTAO journal in 2003. The BANTAO journal has been published biannually since 2003. In the past 10 years, 20 regular issues; 2 supplements (Antalia and Chalkidiki congresses) have been published. Editors of the journal were as follows: 2003-2005--D. Nenov, Editor; 2005-2009--A. Basci, Editor; 2009--Goce Spasovski, Editor. Until now 332 papers have been published. The BANTAO journal is on EBSCO, DOAJ, SCOPUS. After the First Congress of BANTAO, F. Valderrábano, chairman of the EDTA--ERA Registry, at that time, wrote in Nephrology Dialysis Transplantation (1996) 11:740: "Nephrologists of the Balkan countries meet across political frontiers and war fronts--an example to politicians! BANTAO: a new European Medical Association overcomes Political obstacles." Despite the difficulties imposed by major events, such as devastating wars and catastrophic earthquakes in many countries of the Balkan Peninsula BANTAO has made considerable progress. The BANTAO Congress was established as the major scientific and institutional forum for Balkan nephrologists, with its own journal, indicating our will to communicate, to collaborate, to get to know each other and to share our difficulties. Now, we expect further successful work of BANTAO.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

Increased arterial stiffness in patients with nephrotic syndrome.

INTRODUCTION: Nephrotic syndrome (NS) and arterial stiffness (AS) have each been linked with increased risk for cardiovascular diseases. However, there is no data in the literature up-to-date on AS in adult patients with NS. Thus, in this study, we aimed to evaluate the potential associations between AS, volume and nutritional status in patients with NS in comparison to a healthy control group. METHODS: 34 adult patients with newly diagnosed but untreated NS and 34 healthy controls were studied. AS was assessed by carotid-femoral PWV (cf-PWV) and body composition, nutritional status by multifrequency bioelectric impedance analysis (BIA). RESULTS: Mean age was 44.6 ± 18.7 years (18 - 72). Mean cf-PWV was 8.3 ± 2.5 m/s in patients with NS and 6.7 ± 1.1 m/s in controls (p = 0.002) . In univariate analysis, cf-PWV and positively correlated with age, systolic blood pressure, mean arterial pressure (MAP), pulse pressure, body mass index, body fat ratio, waisthip ratio, creatinine, uric acid and negatively with creatinine clearance. In linear regression analysis, only age and MAP predicted arterial stiffness. Total body fluid, extracellular water (ECW), ECW/Height, ECW/body surface area and third space volumes were higher in patients with NS. CONCLUSION: Patients with NS have increased AS and are more hypervolemic compared to the healthy subjects.

Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study.

BACKGROUND: Online haemodiafiltration (OL-HDF) is considered to confer clinical benefits over haemodialysis (HD) in terms of solute removal in patients undergoing maintenance HD. The aim of this study was to compare postdilution OL-HDF and high-flux HD in terms of morbidity and mortality. METHODS: In this prospective, randomized, controlled trial, we enrolled 782 patients undergoing thrice-weekly HD and randomly assigned them in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. The mean age of patients was 56.5 ± 13.9 years, time on HD 57.9 ± 44.6 months with a diabetes incidence of 34.7%. The follow-up period was 2 years, with the mean follow-up of 22.7 ± 10.9 months. The primary outcome was a composite of death from any cause and nonfatal cardiovascular events. The major secondary outcomes were cardiovascular and overall mortality, intradialytic complications, hospitalization rate, changes in several laboratory parameters and medications used. RESULTS: The filtration volume in OL-HDF was 17.2 ± 1.3 L. Primary outcome was not different between the groups (event-free survival of 77.6% in OL-HDF versus 74.8% in the high-flux group, P = 0.28), as well as cardiovascular and overall survival, hospitalization rate and number of hypotensive episodes. In a post hoc analysis, the subgroup of OL-HDF patients treated with a median substitution volume >17.4 L per session (high-efficiency OL-HDF, n = 195) had better cardiovascular (P = 0.002) and overall survival (P = 0.03) compared with the high-flux HD group. In adjusted Cox-regression analysis, treatment with high-efficiency OL-HDF was associated with a 46% risk reduction for overall mortality {RR = 0.54 [95% confidence interval (95% CI) 0.31-0.93], P = 0.02} and a 71% risk reduction for cardiovascular mortality [RR = 0.29 (95% CI 0.12-0.65), P = 0.003] compared with high-flux HD. CONCLUSIONS: The composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups. In a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival.

Alpha-galactosidase A activity levels in Turkish male hemodialysis patients.

Fabry disease is an X-linked lysosomal storage disorder due to deficient activity of alpha-galactosidase A (α-Gal A) leading to renal insufficiency in males. The aim of present study was to investigate the level of α-Gal A activity and to determine the prevalence of Fabry disease in a Turkish male hemodialysis population. The activity of plasma α-Gal A was measured in a group of 808 male hemodialysis patients using fluorimetric methods. Patients with low α-Gal A activity were evaluated clinically and genetic testing was carried out. A correlation with creatinine, uric acid, urea, white blood cell (WBC), and high sensitivity (hs)CRP and α-Gal A activity was also investigated. Plasma α-Gal A activity among this male population undergoing hemodialysis was 7.88 ± 5.18 µM/hour/L (0.40-55.72), significantly lower when compared to controls. No influence of creatinine, uric acid, WBC, or hsCRP on measured α-Gal A activity was reported. Two new Fabry disease patients were identified. Both were previously diagnosed with diabetes mellitus type 2. These findings provide, for the first time, data regarding the prevalence of α-Gal A deficiency (0.24%) in Turkish males receiving hemodialysis.

Effects of thrice weekly nocturnal hemodialysis on arterial stiffness.

OBJECTIVE: In this study, we compared the changes in arterial stiffness in chronic hemodialysis patients treated with 8-h vs. 4-h thrice weekly in-center hemodialysis. METHODS: Sixty prevalent chronic hemodialysis patients assigned to 8-h nocturnal in-center thrice weekly HD (NHD) and 60 control cases assigned to 4-h thrice weekly conventional HD (CHD) were followed for one year. Radial-carotid pulse wave velocity, augmentation index and echocardiography were performed at baseline and 12th month. RESULTS: Mean age of the patients was 49±11 years, 30.8% were female, 27.5% had diabetes mellitus and mean dialysis vintage was 57±47 months. Baseline demographical, clinical and laboratory parameters were similar between groups. During a mean follow-up of 15.0±0.1 months, blood pressure remained similar in both groups while the number of mean daily anti-hypertensive substances decreased in the NHD group. In the NHD group, time-averaged serum phosphorus and calcium-phosphorus product were lower than the CHD group. Pulse wave velocity and augmentation index decreased in the NHD group (from 11.02±2.51 m/s to 9.61±2.39 m/s and from 28.8±10.3% to 26.2±12.1%; p=0.008 and p=0.04, respectively). While augmentation index increased in the CHD group (28.0±9.4 to 31.0±10.7%, p=0.02), pulse wave velocity did not change. Subendocardial viability ratio and ejection duration improved in the NHD group (from 135±28 to 143±25%, p=0.01 and from 294±34 ms to 281±34 ms, p=0.003, respectively), accompanied by regression of left ventricular mass index. In multiple stepwise linear regression analyses, NHD was associated with improvements in augmentation index, ejection duration and subendocardial viability ratio. CONCLUSIONS: These data indicate that arterial stiffness is ameliorated by implementation of longer hemodialysis sessions.

Hypervolemia rather than arterial calcification and extracoronary atherosclerosis is the main determinant of pulse pressure in hemodialysis patients.

INTRODUCTION: Pulse pressure (PP) has been reported as an independent predictor of cardiovascular mortality in hemodialysis patients. In this study, we aimed to investigate association of PP with echocardiographic and vascular structural changes such as atherosclerosis and arterial calcifications in HD patients. PATIENTS AND METHODS: In this cross-sectional study, 108 chronic hemodialysis patients (49 male, 59 female, mean age: 46 ± 13 years) were included. Biochemical analyses, echocardiographic and high-resolution carotid Doppler examinations were done. Aortic wall and coronary artery calcifications were measured with electron beam computed tomography. The degree of carotid artery stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. RESULTS: PP was strongly correlated with systolic (r: 0.82) and diastolic (r: 0.33) blood pressure, left ventricular mass index (r: 0.58), left ventricle end diastolic diameter (r: 0.38) and weakly correlated with aortic wall calcification score (r: 0.26) and carotid plaque score (r: 0.27), but not with coronary artery calcification score. Patients with carotid plaque had higher PP than patients without plaque (50 ± 16 mmHg versus 44 ± 14 mmHg, P = 0.05). Patients were divided into three groups according to aortic wall calcification score. PP was significantly higher in patients with higher aortic wall calcification (54 ± 16 mmHg) than patients with lower aortic wall calcification (44 ± 15 mmHg, P = 0.04). However, on multivariate linear regression analysis for predicting PP, the only significant factor retained was left ventricle end diastolic diameter. CONCLUSION: PP was weakly associated with large vessel calcification and atherosclerosis in hemodialysis patients. The bulk of the effect on PP seems to be due to hypervolemia.

The association between thyroid hormones and arterial stiffness in peritoneal dialysis patients.

BACKGROUND/AIMS: The association between thyroid hormones and arterial stiffness is unclear. In this study, we investigated, for the first time in a large cohort of euthyroid peritoneal dialysis patients, the relationship between thyroid hormone levels and arterial stiffness. METHODS: Fifty-seven patients were enrolled. Serum TSH, free T3 and free T4 levels were measured by chemiluminescence immunoassay method. Pulse wave analysis [augmentation index (AIx) and subendocardial viability ratio (SEVR)] were measured to assess arterial stiffness. RESULTS: Mean age was 49 ± 12.3 years, and 56.1% were female. Mean TSH, fT3 and fT4 levels were 1.97 ± 0.99 mIU/ml, 2.80 ± 0.42 pg/ml and 1.22 ± 0.16 ng/dl, respectively. Mean AIx and SEVR were 22.3 ± 11.3 and 136 ± 21%, respectively. AIx was negatively correlated with residual urine volume (r = -0.372, P: 0.03) and fT3 levels (r = -0.382, P: 0.005). SEVR was correlated only with TSH level (r = -0.394, P: 0.003). In linear regression analysis adjusted for age, gender, history of diabetes and cardiovascular disease and residual diuresis, fT3 level (t = -3.949, P < 0.001) remained associated with AIx. Only TSH level (t = -2.409, P: 0.02) was related to SEVR. CONCLUSION: Low serum fT3 level is associated with arterial stiffness, and high TSH level within the normal range is related to lower SEVR in euthyroid PD patients.

Factors related to pulse wave velocity and augmentation index in chronic hemodialysis patients.

BACKGROUND: Augmentation index (AIx) and pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes and also have been shown to be predictive of cardiovascular disease and total mortality. The aim of our study was to evaluate the relationship between PWV and AIx-HR75, which is the corrected form of AIx according to a heart rate of 75 beats/min, echocardiographic parameters and biochemical parameters in chronic hemodialysis (HD) patients. SUBJECTS AND METHODS: AIx-HR75 and PWV were measured in 556 HD patients by applanation tonometry using the SphygmoCor device. RESULTS: The mean PWV and AIx-HR75 values of the study group were 10.2 ± 2.4 and 28.4 ± 10.2 m/s. A positive correlation was found between PWV and AIx-HR75 (r = 0.214, p = 0.000). AIx-HR75 correlated with age (r = 0.093, p = 0.028), body surface area (BSA) (r = -0.194, p = 0.000), mean arterial pressure (MAP) (r = 0.335, p = 0.000), pulse pressure (PP) (r = 0.212, p = 0.000), cardiothoracic index (r = 0.155, p = 0.016), and presence of left ventricular hypertrophy (r = 0.152, p = 0.001). PWV correlated with MAP (r = 0.208, p = 0.000), PP (r = 0.098, r = 0.021), left ventricular mass (r = 0.105, p = 0.023), and predialysis sodium level (r = -0.105, p = 0.023). In the multivariate analyses, PWV was associated with MAP (t = 3.78, p = 0.000), presence of diabetes (t = 3.20, p = 0.001), and predialysis sodium level (t = -2.06, p = 0.040), and AIx-HR75 was associated with age (t = 2.48, p = 0.014), female sex (t = 3.98, p = 0.000), BSA (t = -2.15, p = 0.033), and MAP (t = 7.02, p = 0.000). CONCLUSION: There is a strong association between MAP and arterial stiffness parameters in HD patients. We feel that efficient control of blood pressure could lead to reduced arterial stiffness in HD patients.

Nephrosclerosis and carotid atherosclerosis: lessons from kidney donor histology.

AIM: Carotid artery intima media thickness (CA-IMT) measurement has been shown to be a safe and reproducible method to assess severity of atherosclerosis. The association between nephrosclerosis and systemic atherosclerosis is not clear. In this study, we investigated the association between CA-IMT and nephrosclerosis in a group of kidney transplant donors. METHODS: Forty seven potential kidney transplant donors were included. CA-IMT was measured by B-Mode ultrasonography. Kidney allograft biopsy samples were obtained during the transplantation operation and chronic glomerular, vascular and tubulointertitial changes were semiquantitatively scored according to the Banff classification. RESULTS: Mean age was 52 ± 12 years and 55% of the cases were younger than 55 years. Mean CA-IMT was 0.74 ± 0.19 mm and 48% had IMT values > 0.75 mm. Chronicty index was ≥5 in 55% of the cases. Chronicity index was higher in cases older than 55 years. Age and CA-IMT were significantly correlated with chronic vascular changes and chronicity index. CA-IMT > 0.75 mm had a 46% sensitivity and 90% specificity to predict nephrosclerosis. Positive and negative predictive values were 85% and 57%, respectively. CONCLUSION: Aging leads to detrimental changes in every part of the vasculature of the human body. CA-IMT is correlated with the level of nephrosclerosis. Measurement of CA-IMT reflects nephrosclerosis especially in older patients.

Statin use is associated with lower inflammation and erythropoietin responsiveness index in hemodialysis patients.

Patients with end-stage renal disease are prone to inflammation and inflammation is related to erythropoietin-stimulating agent hyporesponsiveness and mortality in this population. Statins have been demonstrated to reduce cardiovascular mortality in selected populations of end-stage renal disease patients. These drugs have pleiotrophic effects such as anti-inflammation. In this retrospective analysis, we determined whether the use of statins improves inflammation and inflammation-related anemia in a cohort of hemodialysis patients. Data were analyzed from Fresenius Medical Care Dialysis Clinics in Turkey between 2005 and 2007. Seventy prevalent hemodialysis patients who were on statins at the start of the study and have been on statins during follow-up (statin users) and 1293 patients who were not on statin at the start of the study and had never been prescribed any lipid-modifying drugs during follow-up (statin nonusers) were included in the study. High-sensitive C-reactive protein levels were significantly decreased in statin users (1.50±1.49 vs. 1.33±1.11 mg/L, P=0.05) compared with nonusers (1.93±3.22 vs. 2.05±2.77 mg/L). Hemoglobin levels and the rate of erythropoietin-stimulating agent users were similar. However, the prescribed erythropoietin-stimulating agent dose (31.6±27.5 vs. 47.3±45.2 U/kg/week, P<0.05) and the erythropoietin response index (2.90±2.73 vs. 4.51±4.48 U/kg/week/Hb, P=0.001) were lower in statin users compared with statin nonusers. On stepwise multiple regression analysis, gender, high-sensitive C-reactive protein, duration of hemodialysis, serum ferritin, and statin use were independent determinants of the erythropoietin responsiveness index. Our results suggest that statin treatment leads to lower inflammation and improves hematopoiesis in hemodialysis patients.

Nutritional state alters the association between free triiodothyronine levels and mortality in hemodialysis patients.

BACKGROUND: Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. METHODS: A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. RESULTS: Baseline fT3 was 1.47 ± 0.43 (0.01-2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. CONCLUSIONS: Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.

Relations between malnutrition-inflammation-atherosclerosis and volume status. The usefulness of bioimpedance analysis in peritoneal dialysis patients.

BACKGROUND: Chronic fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with hypertension and left ventricular hypertrophy and dysfunction, which are important predictors of death in dialysis patients. In the present study, we investigated the relationship between nutrition, inflammation, atherosclerosis and body fluid volumes measured by multi-frequency bioimpedance analysis (m-BIA) in PD patients. In addition, we analysed the relationship of extracellular volume values by m-BIA to echocardiographic parameters in order to define its usefulness as a measure of FO. METHODS: Ninety-five prevalent PD patients (mean age 50 ± 13 years, 10 of them diabetic) were enrolled. Extracellular water (ECW), total body water (TBW), dry lean mass (DLM) and phase angle (PA) were measured by m-BIA. Volume status was determined by measuring left atrium diameter (LAD) and left ventricular end-diastolic diameter (LVEDD). Measurement of carotid artery intima-media thickness (CA-IMT) was used to assess the presence of subclinical atherosclerosis. Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. RESULTS: Mean ECW/height was 10.0 ± 1.0 L/m for whole group and 9.3 ± 0.6 L/m in patients with normal clinical hydration parameters. In correlation analysis, markers of nutrition, inflammation and atherosclerosis correlated well with m-BIA parameters. When we used echographically measured LAD (> 40 mm) or LVEDD (> 55 mm) as a confirmatory parameter, a cut-off value of 10.48 L/m ECW/height (78% specificity, with a sensitivity of 77% for LAD and 72% specificity, with a sensitivity of 70% for LVEDD) was found in ROC analysis for the diagnosis of FO. Patients with FO were older and had higher systolic blood pressure, cardiothoracic index, serum CRP level and mean CA-IMT than patients without FO. Patients with inflammation had higher CA-IMT values. In multivariate analysis, only two factors-low urine output and ECW/height-were independently associated with the presence of inflammation. CONCLUSIONS: FO defined by m-BIA is significantly correlated with markers of malnutrition, inflammation and atherosclerosis in PD patients. The indices obtained from m-BIA, especially ECW/height, correlated well with volume overload as assessed by echocardiography and might be a measure worth testing in a properly designed clinical study.

A population-based survey of Chronic REnal Disease In Turkey--the CREDIT study.

BACKGROUND: Chronic kidney disease (CKD) is a growing health problem worldwide that leads to end-stage kidney failure and cardiovascular complications. We aimed to determine the prevalence of CKD in Turkey, and to evaluate relationships between CKD and cardiovascular risk factors in a population-based survey. METHODS: Medical data were collected through home visits and interviews. Serum creatinine, blood glucose, total cholesterol, triglycerides, HDL, LDL and uric acid were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation. RESULTS: A total of 10 872 participants were included in the study. The final analysis was performed on 10 748 subjects (mean age 40.5 ± 16.3 years; 55.7% women) and excluded 124 pregnant women. A low glomerular filtration rate (GFR) (< 60 mL/min/1.73 m(2)) was present in 5.2% of the subjects who were evaluated for GFR, while microalbuminuria and macroalbuminuria were observed in 10.2% and 2% of the subjects, respectively. The presence of CKD was assessed in subjects who gave consent for urinary albumin excretion measurement (n = 8765). The overall prevalence of CKD was 15.7%; it was higher in women than men (18.4% vs. 12.8%, P < 0.001) and increased with increasing age of the subjects. The prevalence of hypertension (32.7% in the general population), diabetes (12.7%), dyslipidaemia (76.3%), obesity (20.1%) and metabolic syndrome (31.3%) was significantly higher in subjects with CKD than subjects without CKD (P < 0.001 for all). CONCLUSIONS: The prevalence of CKD in Turkey is 15.7%. Cardiovascular risk factors were significantly more prevalent in CKD patients.