Huseyin Toz

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.

Effect of Fluid Management Guided by Bioimpedance Spectroscopy on Cardiovascular Parameters in Hemodialysis Patients: A Randomized Controlled Trial

BACKGROUND Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN Prospective, randomized, and controlled study. SETTING & PARTICIPANTS 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS Ambulatory blood pressure data were not available for all patients. CONCLUSIONS Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Treatment of hypertension in dialysis patients by ultrafiltration : Role of cardiac dilatation and time factor

We retrospectively analyzed the blood pressure (BP) and cardiothoracic index (CTi) of 67 hemodialysis patients with hypertension who could be followed up for at least 8 months. A new treatment policy was adopted, aimed at strict volume control. Dietary salt restriction was strongly emphasized. Ultrafiltration (UF) was applied during regular dialysis sessions and sometimes in additional sessions, as long as BP and CTi remained at greater than normal values. All antihypertensive drugs were discontinued at the beginning of treatment. Average BP decreased from 173 +/- 17/102 +/- 9 to 139 +/- 18/86 +/- 11 mm Hg after 6 months and to 118 +/- 12/73 +/- 6 mm Hg after 36 months. Corresponding values for CTi were 52% +/- 4%, 47% +/- 3%, and 42% +/- 4%, respectively. Conventional relatively short dialysis (three times weekly for at least 4 hours) can achieve normal BPs with prolonged effort in most patients, whereas improvement in heart condition facilitates this.

Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis A prospective, case-controlled study

BACKGROUND Longer dialysis sessions may improve outcome in haemodialysis (HD) patients. We compared the clinical and laboratory outcomes of 8- and 4-h thrice-weekly HD. METHODS Two-hundred and forty-seven HD patients who agreed to participate in a thrice-weekly 8-h in-centre nocturnal HD (NHD) treatment and 247 age-, sex-, diabetes status- and HD duration-matched control cases to 4-h conventional HD (CHD) were enrolled in this prospective controlled study. Echocardiography and psychometric measurements were performed at baseline and at the 12th month. The primary outcome was 1-year overall mortality. RESULTS Overall mortality rates were 1.77 (NHD) and 6.23 (CHD) per 100 patient-years (P = 0.01) during a mean 11.3 ± 4.7 months of follow-up. NHD treatment was associated with a 72% risk reduction for overall mortality compared to the CHD treatment (hazard ratio = 0.28, 95% confidence interval 0.09-0.85, P = 0.02). Hospitalization rate was lower in the NHD arm. Post-HD body weight and serum albumin levels increased in the NHD group. Use of antihypertensive medications and erythropoietin declined in the NHD group. In the NHD group, left atrium and left ventricular end-diastolic diameters decreased and left ventricular mass index regressed. Both use of phosphate binders and serum phosphate level decreased in the NHD group. Cognitive functions improved in the NHD group, and quality of life scores deteriorated in the CHD group. CONCLUSIONS Eight-hour thrice-weekly in-centre NHD provides morbidity and possibly mortality benefits compared to conventional 4-h HD.

Endogenous Testosterone and Mortality in Male Hemodialysis Patients: Is It the Result of Aging?

BACKGROUND AND OBJECTIVES Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile. RESULTS Mean testosterone level was 8.69 ± 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P = 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P = 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses. CONCLUSIONS Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

Mycobacterium tuberculosis infection and laboratory diagnosis in solid-organ transplant recipients

Tuberculosis (TB) is an unusual infection in transplant recipients. We evaluated (i) the frequency of TB, (ii) the duration to develop the TB infection, and (iii) clinical consequences, in 380 solid‐organ recipients from January 1995 to December 2000. A total of 10 (2.63%) patients (eight renal, two liver transplant recipients) were found to have post‐transplantation TB. The frequency of TB in this patient population is 8.5‐fold higher than the prevalance in the general Turkish population. Tuberculosis developed within 2–33 months after transplantation, with a median of 15 months. In all of these 10 patients, Mycobacterium tuberculosis (MTB) was isolated from the culture. All the patients continued to have low dose immunosuppressive treatment, and also quadriple antituberculosis treatment [isoniazid (INH), rifampin (RIF), pyrazinamide (PRZ) and ethambutol (ETB)] has been given. The two recipients had died of disseminated form of TB. Relapse was detected in one patient 6 months after the completion of the treatment. As post‐transplant TB infection develops mostly within the first year after transplantation, clinicians should be more careful for early and fast diagnosis and treatment should be started immediately.

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.

Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

BACKGROUND AND OBJECTIVES End-stage renal disease is linked to alterations in thyroid hormone levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low triiodothyronine (T3) levels. These alterations are involved in endothelial damage, cardiac abnormalities, and inflammation, but the exact mechanisms are unclear. In this study, we investigated the relationship between serum free-T3 (fT3) and carotid artery atherosclerosis, arterial stiffness, and vascular calcification in prevalent patients on conventional hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 137 patients were included. Thyroid-hormone levels were determined by chemiluminescent immunoassay, carotid artery-intima media thickness (CA-IMT) by Doppler ultrasonography, carotid-femoral pulse wave velocity (c-f PWV), and augmentation index by Sphygmocor device, and coronary artery calcification (CAC) scores by multi-slice computerized tomography. RESULTS Mean fT3 level was 3.70 ± 1.23 pmol/L. Across decreasing fT3 tertiles, c-f PWV and CA-IMT values were incrementally higher, whereas CACs were not different. In adjusted ordinal logistic regression analysis, fT3 level (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97), age, and interdialytic weight gain were significantly associated with CA-IMT. fT3 level was associated with c-f PWV in nondiabetics but not in diabetics. In nondiabetics (n = 113), c-f PWV was positively associated with age and systolic BP but negatively with fT3 levels (odds ratio = 0.57, 95% confidence interval 0.39 to 0.83). CONCLUSIONS fT3 levels are inversely associated with carotid atherosclerosis but not with CAC in hemodialysis patients. Also, fT3 levels are inversely associated with surrogates of arterial stiffness in nondiabetics.

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).

Left atrial volume predicts mortality in low-risk dialysis population on long-term low-salt diet

BACKGROUND Echocardiography provides insight to the management of end-stage renal disease (ESRD) and might be valuable in assessing the prognosis. We evaluated the predictive value of echocardiography along with clinical findings in a low-risk hemodialysis (HD) population who had been treated with strict salt restriction strategy for blood pressure control. METHODS Study population consisted of a cohort of 555 ESRD patients from 8 HD centers where the same strict volume control strategy applied for blood pressure control. Clinical findings and echocardiography were examined as predictors of mortality for a mean follow-up period of 3 years (29.6 +/- 11.6 months). RESULTS During the follow-up, 89 patients (16%) died. Left atrium (LA) volume index was the only independent echocardiographic predictor of mortality (hazard ratio 1.025, 95% CI 1.001-1.050, P = .042). The other predictors of mortality were age, pulse pressure, diabetes mellitus, and high-sensitivity C-reactive protein. However, when we added interdialytic weight gain (IDWG) ratio to the Cox model, it also appeared as an independent predictor of mortality, whereas LA volume index no longer was. CONCLUSIONS Increased LA volume index emerged as the only independent echocardiographic determinant of mortality in low-risk dialysis patients treated by strict volume control. Close relationship with IDWG ratio indicates the intermittent stretching of atrium between dialysis sessions leading to atrial remodeling. This index is not the result of a single factor such as age, hypervolemia, or left ventricular hypertrophy but reflects the combination of these contributing causes. Therefore, it might be considered as an overall echocardiographic sign of mortality in ESRD.