Ebru Sevinc Ok

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.

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

Background. Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). Methods. BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription–polymerase chain reaction and annexin V staining, respectively. Results. Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. Conclusions. Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations.

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.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

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.

The Impact of Strict Volume Control Strategy on Patient Survival and Technique Failure in Peritoneal Dialysis Patients

Strict volume control strategy provides better cardiac functions and control of hypertension in dialysis patients. We investigated the effect of this strategy on mortality and technique failure in peritoneal dialysis patients over a 10-year period. 243 patients were enrolled. Strict volume control by dietary salt restriction and ultrafiltration was applied. Mean systolic and diastolic blood pressures decreased from 138.4 ± 29.9 and 86.3 ± 16.8 to 114.9 ± 32.3 and 74.7 ± 18.3 mm Hg, respectively. Overall and cardiovascular mortality rates were 48.4 and 29.6 per 1,000 patient-years, respectively. In multivariate analysis, age, diabetes and baseline serum albumin level were independent predictors of overall mortality, and age, diabetes and baseline serum calcium of cardiovascular mortality. Residual diuresis and peritoneal equilibration test values were not related to mortality. Strict volume control leads to lower mortality than comparable series in the literature. Technique survival is better during the first 3 years, but not after 5 years.

Neither oxidized nor anti-oxidized low-density lipoprotein level is associated with atherosclerosis or mortality in hemodialysis patients.

It is anticipated that oxidized low‐density lipoprotein (oxLDL) and anti‐oxLDL are associated with atherosclerosis and mortality. However, data on this issue are controversial and limited. We aimed to investigate the effect of these two markers on the extent and progression of atherosclerosis and mortality in a group of hemodialysis patients. In this prospective observational study with a follow‐up of 36 months, 124 hemodialysis patients were studied. Ninety‐five patients underwent carotid intima media thickness (CA‐IMT) measurement by B‐Mode ultrasonography both at baseline and at the end of the study. oxLDL and anti‐oxLDL were measured by enzyme‐linked immunosorbent assay. The extent and progression of CA‐IMT, along with overall and cardiovascular mortality, were assessed. The mean age at baseline was 54.0 ± 14.8 years, 57.3% male and 20% diabetic. The mean oxLDL and anti‐oxLDL levels were 8.11 ± 3.16 mU/L and 1.30 ± 0.31, respectively. Baseline mean CA‐IMT was 0.82 ± 0.20 mm. Fifteen patients died during a follow‐up period of 28.5 ± 6.6 months, 11 from cardiovascular causes. Only oxLDL, not anti‐oxLDL, was correlated with the extent of atherosclerosis at baseline. However, both had no role in the progression of atherosclerosis. Also, in unadjusted and adjusted models, both parameters were not associated with overall or cardiovascular mortality. Neither oxLDL nor anti‐oxLDL level is associated with the progression of atherosclerosis or mortality in hemodialysis patients.

Relationship between glucose exposure via peritoneal dialysis solutions and coronary artery calcification in non-diabetic peritoneal dialysis patients.

IntroductionVascular calcification is frequent in dialysis patients and is associated with increased mortality. Impaired glucose metabolism is proposed as a contributing factor for vascular calcification. We investigated whether glucose exposure via dialysate may have a role in vascular calcification in non-diabetic peritoneal dialysis patients.MethodWe measured coronary artery calcification by multi-slice computerized tomography in 50 prevalent non-diabetic peritoneal dialysis patients and assessed its relations with fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose exposure from peritoneal dialysis fluid.ResultsTwenty-four patients (48%) had no coronary calcification. When patients were grouped according to the presence or absence of calcification, patients with calcification were mostly men and had higher burden of cardiovascular disease history, vitamin D dose intake, serum calcium, total glucose exposure from dialysis solution, and lower total weekly Kt/Vurea. In multivariate analysis, dialysate glucose exposure was an independent predictor of coronary artery calcification score, besides serum calcium and Kt/Vurea.ConclusionThese data suggest that high glucose exposure from dialysis solution, which is potentially correctable, is a risk factor for vascular calcification in non-diabetic PD patients.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

Hypothyroidism induced severe rhabdomyolysis in a hemodialysis patient.

Hypothyroidism occurs relatively common and is a significant cause of morbidity and mortality during the course of chronic kidney disease. Rhabdomyolysis is a potentially life-threatening condition characterised by necrosis of muscular tissue and rarely associates with hypothyroidism. Here we describe a case of rhabdomyolysis due to severe hypothyroidism in a 56-year-old female hemodialysis patient.