Vascular access complications in daily dialysis: a systematic review of the literature.

Patients treated for end stage renal disease (ESRD) have a shorter life expectancy and a poorer quality of life than the general population. In an attempt to improve outcomes for this patient population, a few novel therapeutic approaches have been undertaken. With hemodialysis, an increase in dialysis frequency and/or time has been associated with improvements in anemia, left ventricular hypertrophy, hypertension, hyperphosphatemia, nutrition and quality of life. Yet, access to these promising hemodialysis modalities has remained limited. The reasons for this are numerous, but one concern is the potential for more frequent vascular access complications with the increased frequency of cannulation for an arteriovenous fistula/graft and connection for a central venous catheter. In this systematic review of the literature, we identified all published studies that included 10 or more patients on daily hemodialysis and reported quantitative data pertaining to vascular access complications. Twelve studies met our inclusion criteria. The overall complication rates associated with vascular access do not appear to be increased and are perhaps even decreased with daily compared to conventional thrice-weekly hemodialysis. Arteriovenous fistulas are the vascular access of choice for daily hemodialysis; however, a non-statistically significant increased complication rate for these accesses was reported in 2 North American studies. The reasons for this are unclear and require further research.

Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences.

The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 microM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.