Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease. Results of a pilot study.

Dual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel (Clp) is the standard treatment to reduce ischaemic coronary events, but in patients with end-stage renal disease (ESRD) the efficacy of Clp remains unclear. Patients with ESRD are at higher risk for coronary artery disease (CAD) and also their post-interventional outcome is worse compared to patients with normal renal function. Little is known about the influence of haemodialysis (HD) on ASA and Clp responsiveness. To assess the effect of HD on ASA- and Clp-responsiveness in patients with documented CAD and ESRD, 31 patients with ESRD (mean age 66.5 ± 1.8 years, 23 male) on DAPT were evaluated for their ASA and Clp responsiveness with the Verify Now System (Accumetrics Inc.) We measured the antiplatelet effect in all ESRD patients at three time points: T1: just before HD; T2: directly after HD; T3: steady state on a HD free day one week after T1. In our study at baseline 10 (32.3%) patients were ASA-low responder (ASA-LR) and 14 (45.2%) patients Clp-low responder (Clp-LR). There was a significant difference in the PRU values before (T1) and immediately after HD (T2) [PRU T1=234 (169; 274) vs PRUT2= 247 (199; 278); pT1,2=0.036; ]. Results were shown as median ARU T1 (25th, 75th percentile) or median PRU T1 (25th, 75th percentile). Hence HD seems to impair responsiveness to Clp, resulting in an increase of 6.5 % Clp-LR. No significant differences in the ARU values at the different time-points were found.

Bismuth coating of non-tunneled haemodialysis catheters reduces bacterial colonization: a randomized controlled trial.

BACKGROUND: Haemodialysis (HD) catheter-related blood stream infections are a major cause of morbidity and mortality in patients with acute and chronic renal failure. METHODS: We conducted a randomized, prospective, double-blinded trial investigating the clinical value of bismuth-coated non-tunneled HD catheters in patients in need of temporary short-term vascular access. A standard catheter (SC) was compared to a surface-modified, bismuth-film-coated catheter (FCC). After removal of the catheter for any reason, both arterial and venous lumina were rinsed and the fluid cultured for detection of bacterial colony-forming units (CFU). The catheter tip was placed in a tube containing sterile saline, sonicated and shortly centrifuged to remove debris (3 min at 1000 g). The supernatant was cultured and assayed for DNA content. RESULTS: Seventy-seven patients in three HD units were randomized. Thirteen patients suffered from acute renal failure, 60 patients from chronic renal failure, and four patients without renal insufficiency were treated with plasma exchange. The time to catheter removal was not significantly different between groups, with a mean of 18.5 +/- 2 days for SC and 15.1 +/- 2 days for FCC. In most cases, the reasons for catheter removal were related to no further need for extracorporeal therapy or establishment of a permanent vascular access. Six catheters for SC and four catheters for FCC were removed because of presumed infection. Bacterial colonization was significantly lower for coated catheters compared to standard catheters, both for cultured catheter tips as well as for CFU in rinse fluids (P < 0.05). CONCLUSIONS: Surface modification with bismuth film reduces bacterial colonization of temporary non-tunneled HD catheters in a clinical trial. Larger trials with these modified catheters are justified to further investigate the effect on catheter-related infections, complications and costs.

Laparoscopic-assisted placement of peritoneal dialysis catheters: implantation technique and results.

BACKGROUND: Peritoneal dialysis is a generally accepted method for the treatment of patients with end-stage renal failure. The laparoscopic placement of peritoneal dialysis catheters is a well-established technique and offers some advantages, such as a safer placement of the catheter, less post-operative complications, and a longer functional survival, compared to the conventional open technique. The aim of this study was to describe our implantation technique and to determine the results of our approach. PATIENTS AND METHODS: Between January 2000 and February 2006, 47 patients with end-stage chronic renal failure underwent a laparoscopic peritoneal dialysis catheter insertion procedure. Perioperative and follow-up data were collected prospectively. RESULTS: The mean operating time was 35 minutes (range, 16-100). There was no perioperative morbidity. Nine (19.1%) patients experienced 10 mechanical complications: fluid leakage in 6 (12.8%) patients, acute hydrothorax in 1 (2.1%), catheter tip migration in 2 (4.3%), and catheter obstruction in 1 (2.1%) patient. Episodes of peritonitis were observed in 5 (10.6%) patients. One (2.1%) patient developed a catheter infection. In 3 (6.4%) patients, a port site hernia occurred that required surgical repair, 5 (10.6%) patients underwent laparoscopic revisions owing to mechanical complications, 9 (19.1%) patients underwent renal transplantation, and 6 (12.8%) patients died during the later follow-up. After a mean follow-up time of 17 months (range, 2-76), 30 (63.8%) catheters are still in use for dialysis. CONCLUSIONS: The functional outcome of the dialysis catheters was satisfactory in the majority of patients in this study. The described technique for catheter implantation is simple and safe, and in our opinion, the laparoscopic technique should be considered as the method of choice in patients with end-stage chronic renal failure.

A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a.

In sepsis, endotoxin, interleukin 6 (IL-6), and complement-activation product 5a (C5a) trigger inflammatory cascades resulting in monocytic deactivation. When this occurs, the outcome is often uncontrolled infection, multiple organ dysfunction, and death. We tested here whether simultaneous reduction of systemic endotoxin, IL-6, and C5a levels could be achieved via selective extracorporeal immunoadsorption (IA) and whether this would restore monocytic responsiveness and improve organ function. Therefore, 33 patients with severe sepsis or septic shock were enrolled in a prospective, 1:2 case-control matched, blinded endpoint evaluation trial. In addition to best supportive care, 11 of these patients (mean age, 57.8 +/- 2.2 years; Acute Physiology and Chronic Health Evaluation II score, 23.7 +/- 1.6) received simultaneous endotoxin IA, IL-6 IA, and C5a IA on 5 consecutive days for 7.5 h each. Our observational end points were the course of monocytic immunity (monocytic HLA-DR expression) and other indices of inflammation and disease severity. In patients receiving IA, the mean circulating level of IL-6 was reduced from 361.7 +/- 116.0 to 38.2 +/- 15.2 pg/mL (P = 0.02), and of C5a from 297.6 +/- 43.1 to 79.2 +/- 14.5 ng/mL (P < 0.001). Two indices of endotoxemia were reduced also. Treated patients had lower C-reactive protein and Acute Physiology and Chronic Health Evaluation II scores at day 7 (P = 0.004 and P = 0.0001, respectively). Monocytic HLA-DR improved in the treated patients but not in controls (P < 0.0001). Under treatment, HLA-DR was found to recover in all patients with immunoparalysis (4,993.6 +/- 1,162 to 15,295.3 +/- 2,197 molecules per cell; P = 0.002). Here, we demonstrate that simultaneously reducing circulating endotoxin, IL-6, and C5a levels by selective IA reverses monocytic deactivation and improves organ system functions. This novel strategy might open a new therapeutic avenue for an interventional extracorporeal treatment of patients with sepsis.