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.

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.

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.

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.

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.

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.

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.

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.

The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis.

BACKGROUND: Most haemodialysis (HD) centres use anti-hypertensive drugs for the management of hypertension, whereas some centres apply dietary salt restriction strategy. In this retrospective cross-sectional study, we assessed the effectiveness and cardiac consequences of these two strategies. METHODS: We enrolled all patients from two dialysis centres, who had been on a standard HD programme at the same centre for at least 1 year. All patients underwent echocardiographic evaluation. Clinical data were obtained from patients' charts. Centre A (n = 190) practiced 'salt restriction' strategy and Centre B (n = 204) practiced anti-hypertensive-based strategy. Salt restriction was defined as managing high blood pressure (BP) via lowering dry weight by strict salt restriction and insistent ultrafiltration without using anti-hypertensive drugs. RESULTS: There was no difference regarding age, gender, diabetes, history of cardiovascular disease and efficiency of dialysis between centres. Antihypertensive drugs were used in 7% of the patients in Centre A and 42% in Centre B (P < 0.01); interdialytic weight gain was significantly lower in Centre A (2.29 +/- 0.83 kgversus 3.31 +/- 1.12 kg, P < 0.001). Mean systolic and diastolic blood pressures were similar in the two centres. However, Centre A had lower left ventricular (LV) mass (indexed for height(2.7): 59 +/- 16 versus 74 +/- 27 g/m(2.7), P < 0.0001). The frequency of LV hypertrophy was lower in Centre A (74% versus 88%, P < 0.001). Diastolic and systolic functions were better preserved in Centre A. Intradialytic hypotension (hypotensive episodes/100 patient sessions) was more frequent in Centre B (11 versus 27, P <0.01). CONCLUSIONS: This cross-sectional study suggests that salt restriction and reduced prescription of antihypertensive drugs may limit LV hypertrophy, better preserve LV functions and reduce intradialytic hypotension in HD patients.

The influence of dialysate calcium on progression of arterial stiffness in peritoneal dialysis patients.

BACKGROUND: One of the origins of cardiovascular disease in dialysis patients is arterial stiffness. The aim of our study was to assess the relationship between the calcium content of peritoneal dialysis (PD) solution and arterial stiffness. PATIENTS AND METHODS: We enrolled into the study 49 PD patients who had been treated with the same PD solution for the preceding 6 months. The calcium content of the PD solution was 1.25 mmol/L in 34 patients (low-Ca group) and 1.75 mmol/L in 15 patients (high-Ca group). Study patients were followed for 6 months on the same PD prescription. Arterial stiffness was assessed by measurement of augmentation index (AI) and brachial pulse wave velocity (PWV) at baseline and at month 6 (SphygmoCor: Atcor Medical, West Ryde, NSW, Australia). Demographic data were recorded from patient charts. RESULTS: Mean age of the whole group was 51 +/- 11 years, prevalence of diabetes was 14%, duration of PD was 43 +/- 30 months, percentage of women was 45%, and percentage of patients using a cycler was 33%. We observed no differences between groups with regard to those variables or creatinine clearance, residual renal function, Ca, phosphorus, parathormone, C-reactive protein, lipid parameters, and use of phosphate binder with or without Ca content. Mean arterial pressure was higher in the high-Ca group, but the difference was not statistically significant (100 +/- 22 mmHg vs 88 +/- 18 mmHg, p = 0.06). At baseline, AI was significantly higher in the high-Ca group than in the low-Ca group (27% +/- 10% vs 21% +/- 9%, p < 0.05). Measurements of PWV were not different between the groups (8.4 +/- 1.1 m/s vs 8.5 +/- 1.7 m/s). Measurement of arterial stiffness parameters at month 6 revealed that PWV had increased in the high-Ca group (to 9.6 +/- 2.3 m/s from 8.4 +/- 1.1 m/s, p < 0.05), but had not changed in the low-Ca group (to 8.2 +/- 1.9 m/s from 8.5 +/- 1.7 m/s). The AI did not change in either group. CONCLUSIONS: These data suggest that Ca exposure through PD solution plays a role in the progression of arterial stiffness, which may be related to increased vascular calcification.

Is it necessary to check outcomes to improve quality of care? The example of anemia management.

The aim of this study was to verify the importance of continuously monitoring the level of adherence to the anemia guideline recommendations in order to improve not only quality of care but also patient safety. Data presented in this investigation were gained through the FME database EuCliD which contains the clinical data of over 24,000 prevalent patients under treatment at the time of the analysis in 344 dialysis centres in 15 countries. Patient data from 4 countries (United Kingdom, Turkey, Italy, Portugal) was used for this study. The parameter selected was anemia control. The level of hemoglobin (Hb) was considered as the quality indicator for anemia, the target being an Hb level >11 g/dL, for UK centres the target was >10 g/dL. All new patients commencing hemodialysis between October 2003 and September 30, 2004 with the previous follow-up of less than one month and without previous blood transfusion were considered. A total of 902 patients were enrolled. The study showed that 4 to 6% of the Italian, Portuguese and British patients treated in FME clinics received a blood transfusion during the first year of follow-up. This is consistent with reports by USRDS that only 3.3% of ESRD patients received at least 1 transfusion per quarter in 1992 after erythropoietin became available and was prescribed to 88% of patients. About 18% Turkish patients, required blood transfusions during the first year of follow-up on hemodialysis, which is more comparable with USRDS data reported in 1989, when 16% of patients needed at least 1 transfusion quarterly. In conclusion, the practice of blood transfusion for hemodialysis patients is still frequent especially in elderly patients.

Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.

AIM: Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC). METHODS: Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied. RESULTS: Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis. CONCLUSION: The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.

Interdialytic blood pressure obtained by ambulatory blood pressure measurement and left ventricular structure in hypertensive hemodialysis patients.

Unlike in subjects with normal renal function, the relationship between hypertension and cardiovascular morbidity and mortality in dialysis patients is still being debated. In order to clarify this issue, we performed 44-hour ambulatory blood pressure measurements (ABPM) during the interdialytic period in a group of 164 hypertensive patients, the blood pressure (BP) control based on conventional antihypertensive strategy previously, on chronic hemodialysis treatment in the Mediterranean region of Turkey. These results were then compared with their echocardiographic data. This is a cross-sectional analysis. The mean ABPM during 44 hours was close to the manually measured predialysis value, but there was a gradual increase in the ABPM values in the interdialytic period. When divided into a group with mild or no left ventricular hypertrophy (LVH) (45 patients) and severe LVH (119 patients), the latter had significantly higher BP levels in all separate periods, while the difference in predialysis BP was not significant. Patients with severe LVH had larger left atrium and left ventricular diameters, and consumed more antihypertensive drugs. Systolic BP during the night before dialysis showed the strongest relation to LVH, but interdialytic weight gain was also independently related to LVH. Yet, 56% of the patients with systolic BP <135 had severe LVH. There is not only an association between BP and presence of LVH, but it is shown that volume expansion is also an important independent determinant of LVH. This may explain the difficulty in identifying hypertension as a cardiac risk factor in these patients.

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.

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.

Impact of volume control on left ventricular hypertrophy in dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH), which strongly predicts cardiac mortality, is seen in more than 60% of end-stage renal disease patients. The aim of this study was to prospectively investigate the effect of salt restriction and strict volume control on blood pressure and LVH. METHOD: Nineteen hypertensive patients on chronic hemodialysis (HD) treatment (age 52 +/- 17 years, 7 women) were included in the study. Treatment consisted of 12-h HD per week, during which as much ultrafiltration (UF) was applied as possible without an excessive blood pressure (BP) drop. Special attention was given to dietary salt restriction. Predialysis mean BP (MBP), body weight (BW), cardio-thoracic index (CTI) and echocardiographic results were recorded at baseline and after 6 and 12 months. RESULTS: All patients reached acceptable BP (< 140/90 mmHg) within three months (10-75 days) with our strict volume control strategy. Mean pre-dialysis BP was 127 +/- 17/78 +/- 9 mm Hg at baseline, 120 +/- 9/75 +/- 6 mm Hg at the 6th month and 118 +/- 11/73 +/- 5 mm Hgat the 12th month. The incidence of symptomatic hypotension gradually decreased from a mean of 22% to 11% and 7%, respectively during follow-up. Left ventricular mass index decreased from 164 +/- 64 to 112 +/- 36 g/m2. CTI, left atrial, left ventricular systolic and diastolic diameters significantly decreased in all patients. Inter-dialytic weight gain was 930 +/- 70 g/day in the follow-up period. Hematocrit did not significantly differ at the first, second and last visits. CONCLUSION: Normal BP and improvement of cardiac structure, in particular a reduction of LVH could be reached in all our patients by intensifying salt restriction and UF.