Ali Basci

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.

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 m2) 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.

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.

CRYPTOSPORIDIOSIS AND BLASTOCYSTOSIS IN RENAL TRANSPLANT RECIPIENTS

Some intestinal parasitic infections are frequently seen in renal transplant recipients. Parasites such as Cryptosporidium spp. and Blastocystis hominis are often asymptomatic or responsible for limited infections in normals, but may cause prolonged and heavy infections with gastrointestinal complaints, mainly diarrhea, in immunocompromised patients. Such infections can often not be detected by routine diagnostic procedures, but special concentration and staining methods are needed. We investigated 115 fecal specimens from 69 renal transplant recipients and 42 fecal specimens from 42 control cases. Of the 69 recipients, 27 (39.1%) had B. hominis and 13 (18.8%) had Cryptosporidium spp. in at least one fecal specimen. Prevalence of symptomatic Cryptosporidium infections was significantly higher in the renal transplant recipients, when compared with the control group (p < 0.05). Special parasitological procedures must be performed in immunocompromised patients with chronic gastrointestinal complaints. Disappearance of symptoms after antiparastic drugs in some of 16 symptomatic patients are described, suggesting that these infections are more pathogenic in transplant recipients.

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.

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).

Renal side-effects of long-term lithium treatment.

The beta 2-Mg (beta 2-microglobulin) and GAG (glycosaminogyclan) excretions in 107 patients with bipolar disorder who had been on lithium treatment for 1-15 years were compared with 29 matched psychiatric control patients. 24-h urine volume, urine beta 2-Mg, GAG values were significantly higher, and maximal urinary osmolality was significantly lower in patients on lithium than in controls. No relationship was found between creatinine clearances and duration of illness, duration of lithium treatment and daily lithium dosages. Duration of lithium treatment was not related to the concentrating capacity. The beta 2-Mg excretion rates were significantly higher in patients with manifest polyuria and with severe concentration defect.

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.

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.

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.