Devrim Bozkurt

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.

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.

The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats.

INTRODUCTION Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats. METHODS 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 ml isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated. RESULTS Although the MMF and resting groups showed beneficial effects on ultrafiltration and D1/D0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGFβ1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm2 of submesothelial area, decreased in the treatment group. CONCLUSIONS MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.

Octreotide lessens peritoneal injury in experimental encapsulated peritoneal sclerosis model

Aim:  Encapsulated peritoneal sclerosis is characterized by neoangiogenesis and fibrosis. Octreotide, a somatostatin analogue is a well‐known antifibrotic, antiproliferative and anti‐angiogenic agent. The aim of the study is to evaluate the effects of octreotide in encapsulated peritoneal sclerosis‐induced neoangiogenesis and fibrosis and compare the results with resting.

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.

A)typical (Extra) Pulmonary Tuberculosis in Kidney Patients

Tuberculosis is still a major health problem especially among immunocompromised hosts. Another problem is making diagnosis due to the unexpected presentation and localization of disease. Extrapulmonary disease may clinically and radiographically mimic other infectious or neoplastic diseases. In this report we presented three tuberculosis cases; a kidney allograft recipient and two patients with end stage renal disease including soft tissue abscess, lytic bony lesions and pathological fractures without any pulmonary symptoms. Tuberculosis should be kept in mind during atypical generalized inflammatory conditions especially in immunocompromised hosts. Atypical localization and symptomatology may arise due to the more potent immunosuppressive agents. Delay in diagnosis may cause significant mortality and morbidity in patients with high risk. Starting anti-tuberculosis treatment empirically in most cases due to the difficulties in establishing diagnosis is another problem. Classical anti-tuberculosis treatment is sufficient to control disease in most cases. Early management may be a life saving approach.