Platelet thrombus formation in patients with end-stage renal disease before and after hemodialysis as measured by the total thrombus-formation analysis system.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) often experience bleeding. However, mechanisms behind this bleeding tendency are incompletely understood but may involve platelet dysfunction. We, therefore, studied platelet-dependent thrombus formation in flowing whole blood inside a microchip coated with collagen, and its association with circulating von Willebrand factor (VWF). METHODS: Blood samples were obtained in 22 patients before and after HD. The area under the 10 min flow pressure curve in a microchip (AUC10) reflecting total platelet thrombogenicity was measured, using the Total Thrombus-formation Analysis System (T-TAS01). AUC10 < 260 indicates platelet dysfunction. VWF activity and antigen in plasma were also assayed. RESULTS: VWF levels were moderately elevated and increased further after HD (P < 0.01 or lower). In contrast, AUC10 before and after HD was < 260 in 17/22 patients and < 130 in 15/22 patients, with no statistically significant difference in pre- vs post-HD measurements, indicating reduced platelet thrombogenicity, but with some variability as 5/22 patients showed normal platelet responsiveness. AUC10 and VWF activity or antigen levels in plasma were not correlated, either before or after HD. CONCLUSIONS: Most ESRD patients display moderate-to-severe platelet dysfunction as assessed by shear-induced platelet-dependent thrombus formation with T-TAS01. HD does not influence platelet function despite HD-induced elevations in VWF. T-TAS01 should be further evaluated as a tool in the assessment of bleeding risk in patients on HD.

Protein Carbonyl Content Is a Predictive Biomarker of Eccentric Left Ventricular Hypertrophy in Hemodialysis Patients.

High prevalence of left ventricular hypertrophy (LVH) and elevated oxidative stress are associated with poor outcomes in chronic hemodialysis patients. Abnormal left ventriculаr geomеtry and different geometric patterns play an important role as well. Our study analyzed the role of oxidative stress on myocardial remodeling in these patients. Plasma malondialdehyde (MDA), protein carbonyl (PC) content, and total antioxidative capacity (TAC) were investigated in 104 hemodialysis patients together with transthoracic echocardiography. Compared to patients with normal ventricular geometry, patients with LVH had increased MDA and PC plasma concentration. Multivariate analysis demonstrated that protein carbonyls, as biomarkers of oxidative protein modification, were an independent predictor of eccentric hypertrophy (eLVH), including higher LV end-diastolic diameter and LV end-diastolic volume, (ß = 0.32 and ß = 0.28, p < 0.001 for both). The incidence of eLVH increased progressively from the lowest to the highest baseline PC tertile (p < 0.001 for the trend) and the subjects in the former group showed a 76% greater risk of developing eLVH compared to their counterparts. After further adjustment for the potential mediators, PCs carried eLVH odds (95% confidence interval (CI)) of 1.256 (0.998-1.514), per standard deviation increase. High plasma protein carbonyls levels are a significant independent predictor of eccentric LVH in chronic hemodialysis patients.

Elevated Serum Ferritin Levels Are Predictive of Renal Function Recovery among Patients with Acute Kidney Injury.

Oxidative stress (OS) frequently contributes to the development of acute kidney injury (AKI). Iron can promote oxidative stress and tissue injury by catalyzing free reactive oxygen species (ROS) generation and increasing the steady-state concentration of these potent oxidants. The anticipated role of ferritin is to protect from OS by sequestering iron and limiting its involvement in reactions that generate ROS. In this prospective study, we aimed to investigate the association between serum ferritin levels and kidney function recovery among patients with AKI. Renal recovery was determined as a return of serum creatinine to less than 1.25 times the baseline value after 90 days of follow-up. One hundred twelve patients (72 males and 40 females, 63.68 ± 10.6 years old) were included in the final analysis. They were divided into AKI recovery (n = 76) and non-recovery groups (n = 36). Ferritin levels on admission were higher in AKI recovery group [284 (IQR 153-525) ng/mL] compared with the non-recovery group [127.4 (IQR 30-243) ng/mL], p < 0.001. Serum ferritin levels and the renal recovery significantly positively correlated (r = 0.72, p < 0.001). In multiple linear regression analysis, higher serum ferritin was associated with renal function recovery (OR 3.68, CI 2.02-3.97, p < 0.001). The optimal cut-off point of 240.5 ng/mL was determined for serum ferritin, which showed a sensitivity of 75.8% and a positive predictive value of 90%. In conclusion, serum ferritin levels on admission may be used as a prognostic marker for predicting renal recovery in AKI patients.

Population Pharmacokinetics of Bisoprolol in Hemodialysis Patients with Hypertension.

The aim of our study was to estimate clearance of bisoprolol and reveal the factors that could influence its pharmacokinetic (PK) variability in hypertensive patients on hemodialysis, using the population PK analysis. Parameters associated with plasma concentration of bisoprolol at steady state were analyzed in 63 patients (mean age 62.12 years, mean total weight 69.63 kg) who were hypertensive and on hemodialysis due to severe renal failure using non-linear mixed-effect modeling with ADVAN1 subroutine. The final regression model for the clearance of the drug included only creatinine clearance (CLcr) out of 12 tested covariates. The equation that describes CL of bisoprolol is the following: CL (l/h) = 0.12 + 6.33 * CLcr. These findings suggest that the routine measuring of serum creatinine level may be used to facilitate administration of bisoprolol in patients on hemodialysis.

How the duration period of erythropoietin treatment influences the oxidative status of hemodialysis patients.

BACKGROUND: End-stage renal disease is a state of enhanced oxidative stress (OS) and hemodialysis (HD) and renal anemia further augment this disbalance. Anemia correction with erythropoietin (EPO) may improve oxidative status. However, there is no evidence of time dependent effects of EPO therapy on redox status of HD patients. OBJECTIVE: The aim of this study was to evaluate whether the duration of EPO treatment may affect OS parameters in uremic patients. PATIENTS AND METHODS: 104 HD patients and 29 healthy volunteers were included. Patients were divided into 3 groups according to the duration of EPO treatment. Forth group consisted of HD patients without EPO treatment. Plasma and erythrocyte malondialdehyde (MDA, MDA(rbc)), reactive carbonyl groups (RCG), plasma sulfhydryl (-SH) groups and total antioxidative capacity (TAC) levels were evaluated. RESULTS: HD patients both with and without EPO treatment, showed a significant increase in all oxidative parameters without significance between EPO treated and -untreated group. The decrease in MDA and MDA(rbc) levels coincided with the duration of EPO treatment. A negative correlation was observed between the duration of EPO treatment and serum MDA (r=-0.309, p=0.003). Increasing periods of EPO treatment were associated with decrease in RCG, without significance between EPO groups. Increase in TAC accompanied increasing durations of EPO treatment, with EPO treatment for more than 24 months causing the most striking changes (p<0.05). There were no significant differences in -SH levels between EPO subgroups. CONCLUSION: Our results suggest that long term administration of EPO attenuated the lipid peroxidation process and restored the levels of antioxidants.