Intradialytic Drug Removal by Short-daily Hemodialysis

Despite improvements in dialysis machine and filter technology and refinements in providing an adequate "dose" of HD, patients receiving thrice-weekly hemodialysis (HD) have an alarming 20% annual mortality rate. Concomitant with this high mortality rate, patients with end stage renal disease (ESRD) also endure poorer qualities of life and medical complications such as anemia, infection, accelerated cardiovascular disease and bone disease associated with calcium-phosphorus disequilibrium. Recently, quotidian dialysis regimens, which include both the short-daily and nocturnal modalities, have emerged as dialytic approaches that appear to improve the patient's quality of life and attenuate the medical complications associated with ESRD1- 4. Specifically, recent studies have documented improvements in a patient's quality of life as measured by both general instruments (SF-36) and by renal disease specific tools. Short-daily HD regimens have also led to improvements in anemia allowing reductions in doses of erythropoietin. Similarly, in one study blood pressure control was improved with short-daily HD to such an extent that the majority of the study patients were eventually off of all antihypertensive medications. Phosphorus control has also improved with hemeral and especially nocturnal short-daily regimens. In one study of patients receiving nocturnal HD, all of the patients were completely weaned of their phosphorus binders and actually required intradialytic phosphorus supplementation. Finally, nutritional status also appears to be enhanced in studies of short-daily HD with increases in both appetite and weight gain observed. The medical benefits observed in these studies are believed to be secondary to the enhanced solute clearance and better extra-cellular volume management that short-daily HD affords as compared to intermittent HD. In particular, the nocturnal regimen appears especially effective since it provides a higher "dose" of HD than its hemeral counterpart.

According to the most recent United States Renal Data Service (USRDS) compilation, infection continues to exact a heavy toll among dialysis patients. The most recent USRDS mortality rate attributable to sepsis for dialysis patients was 27.0%. Despite the reported improvements in quality of life and medical complications provided by short-daily HD, infection will likely remain a persistent medical issue for dialysis patients. As a result, the appropriate provision of antibiotic therapy to patients receiving hemodialysis will remain paramount. Currently, there are no studies that have evaluated the pharmacokinetics of the commonly used antibiotics in the growing short-daily HD population. With no specific guidelines, pharmaco-kinetic estimations and frequent drug levels have been utilized to direct antibiotic dosing. This is likely not the best therapeutic approach and may not be the most cost-effective. This study will attempt to address this deficit in the clinical knowledge for three commonly used antibiotics, vancomycin, levofloxacin and gentamicin. The drug dosing guidelines developed from this study will ensure that this patient population receives the optimum antibiotic therapy to treat their infection in the most cost-effective manner.

Utilizing drug level data from an as yet unpublished study on the removal of gentamicin by thrice weekly dialysis, we configured the pharmacokinetic modeling software ADAPT to compare the serum levels of gentamicin during intermittent and short-daily HD. For the short-daily HD simulation, the ADAPT software demonstrated two periods of increased removal of gentamicin corresponding to the two sessions of short-daily HD (Figure 1). The purpose of the present study is to demonstrate in vivo that this is indeed true for gentamicin, as well as for vancomycin and levofloxacin.