The Role of Hemostatic Factors in Atherosclerosis in Patients with Chronic Renal Disease.

INTRODUCTION: Atherosclerotic cardiovascular disease remains the leading cause of increased morbidity and mortality observed in chronic kidney disease (CKD) patients. Endothelial dysfunction (ED) is thought to be a key initial event in the development of atherosclerosis. The aim of this study was to evaluate the potential role of hemostatic factors in atherosclerosis, thrombosis and cardiovascular complications in patients suffering from chronic renal disease. METHODS: The study was conducted on 50 renal patients divided into two groups of equal size. Group 1 consisted of 25 patients with end-stage renal disease (ESRD) on regular hemodialysis. Group 2 consisted of 25 chronic renal disease patients on conservative treatment. Twenty age- and sex-matched healthy subjects were included in the study to serve as a control group. Thrombomodulin (TM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and hsCRP were assessed. High-resolution B-mode ultrasonography of both the common and internal carotid arteries to measure carotid intima media thickness (CIMT) was performed on all subjects. RESULTS: There were highly significant increases in hsCRP, TM, vWF, tPA and PAI-1 in both patient groups compared to the control group (P<0.01 for all except for TM between group 2 and 3 P<0.05) with significant increase in group 1 compared to group 2 (P<0.01). In addition, there was a highly significant increase in CIMT in both patient groups compared to the control group (P<0.01) with a significant increase in group 1 compared to group 2 (P<0.05). The study revealed significant positive correlation of hemostatic factors (TM, vWf, PAI-1 & t-PA) with creatinine, urea, hsCRP & CIMT. CONCLUSION: CKD patients have increased risk of atherosclerosis as measured by CIMT, which is used as a surrogate marker of early atherosclerosis and has been shown to be a strong predictor of future myocardial infarction and stroke. They have high levels of TM, vWF, tPA, PAI-1 that correlate with kidney function, hsCRP and CIMT. Therefore, these abnormalities in hemostasis may account for the increased risk of atherothrombosis in these patients. The elevated hsCRP levels and their correlation to hemostatic factors and CIMT might provide an important clue to link a systemic marker of inflammation to atherosclerosis. Further research is required to better understand the procoagulant state in patients with CKD.

Novel troponin-like biomarkers of acute kidney injury.

Acute kidney injury (AKI) is a common and serious condition in both the inpatient and outpatient settings, and its diagnosis depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has limited our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has realized a number of potential biomarkers. For example, neutrophil gelatinase-associated lipocalin is emerging as an excellent stand alone troponin-like biomarker in the plasma and urine for predicting and monitoring clinical trials and in the prognosis of AKI. In recent years, a number of new biomarkers of AKI with more favorable test characteristics than creatinine have been identified and studied in a variety of experimental and clinical settings. This review will consider the most well-established biomarkers of AKI.

Biocompatible dialysis membranes and oxidative stress in patients wih end-stage renal disease on maintenance haemodialysis.

Oxidative stress has been shown in (ESRD) patients specially those receiving regular haemodialysis (HD) in relation with an increased production of toxic free radicals due to membrane-induced complement leukocyte activation. An imbalance between oxidants and antioxidans has been suggested in uremic patients on HD. The respective influence of uremia and dialysis procedure has not been evaluated. Studies that have probed into the mechanism of oxygen radical production have implicated the bio-incompatibility of dialysis membranes. The effect of different dialysis membranes on lipid, lipoproteins, lipid peroxidation and total antioxidant capacity in ESRD patients on regular HD was studied. One hundred subjects were selected; 20 healthy controls, 20 chronic renal failure (CRF) patients on conservative drug management and 60 CRF patients on maintenance HD (20 dialyzed by polysulfone, 20 by hemophan and 20 by cuprophane membranes). All patients were matched for age, sex, gender and etiology of ESRD and HD patients for duration of dialysis. In addition to routine tests (Hb% and creatinine clearance in healthy control group and CRF patients on conservative management), total cholesterol, triglycerides, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B), serum malondialdehyde (MDA) and plasma total antioxidant status (TAS) were estimated. MDA was significantly higher and TAS was lower in uremic patients treated conservatively or by HD than in controls. MDA was significantly higher in HD than CRF patients on conservative management with least significant difference in HD patients treated by polysulfone followed by hemophan and then cuprophane membrane, while only cuprophane group showed lower levels of TAS compared to CRF patients on conservative management. HDL-C and Apo A was higher in polysulfone and hemophan than cuprophane group while triglyderide was lower. Polysulfone group showed lower levels of LDL-C than both cuprophane and hemophane groups thus providing less atherogenic lipid profile. There was a positive correlation between Hb% and TAS and a significant negative correlation between MDA and Hb%. There was a significant negative correlation between TAS and duration of dialysis in HD patients. In CRF patients on conservative management we obtained a significant positive correlation with TAS and a significant negative correlation with MDA.