The frequency of dialysis was established at three times a week in 1965,1 and this frequency has been used in most centers around the world. Soon after the establishment of this dialysis schedule, an analogue simulation concluded that daily (also known as quotidian) short dialysis sessions would be more effective than thrice-weekly longer dialysis sessions in lowering the average concentration of various markers, such as urea, which rapidly equilibrate among body-fluid compartments.2 With thrice-weekly hemodialysis, the relatively long interval between dialysis sessions results in a “peak-and-valley” effect characterized by fluctuations in the levels of toxins and body-fluid volume, affecting the ability of patients to tolerate dialysis sessions.3 Shorter but more frequent dialysis sessions appeared to be a potential solution to this problem.

Early research (from March 1969 through May 1973) on frequent hemodialysis in patients with end-stage renal disease, in which the before-and-after methods of study were used, showed that more frequent dialysis improved clinical and laboratory variables.4 The results were sufficiently impressive that it was predicted that daily dialysis would soon be the standard of care.4,5 The number of patients undergoing dialysis daily has since increased, but not at the predicted pace.

One reason for a slow pace may be the cost of daily dialysis. A request for an increase in reimbursement from Medicare by proponents of daily dialysis led to a National Institutes of Health Task Force on Daily Dialysis, in April 2001 (Order #342, Conference ID 108).6 That body reached a consensus that observational studies provided insufficient evidence to change the standard of care and that a randomized, controlled trial was indicated. The practitioners involved in delivering daily dialysis were already convinced of its substantial clinical advantage. In contrast, others still thought that a randomized, controlled trial would be required to prove the superiority of one method over another.

In this issue of the Journal, Chertow et al. report the results of a randomized trial that compared outcomes with different frequencies of dialysis.7 The investigators anticipated challenges in enrollment. Such difficulty in patient recruitment is not uncommon when randomized, controlled trials compare different treatment methods. Chertow et al. enrolled 378 patients and randomly assigned 245; it is unclear how many potential candidates were screened and how many declined to undergo randomization. Whether any patients undergoing peritoneal dialysis were approached is not stated. The patients in the study were in better health than are those in the general U.S. population who are undergoing hemodialysis, as shown by the fact that the rate of death in the control (thrice-weekly) group at 1 year was only 7.5%, whereas the rate of death in the wider U.S. population undergoing hemodialysis is more than 18.5%.

In this randomized, controlled trial, a similar technique was used for dialysis six times per week and for thrice-weekly dialysis, although many would argue that both the required dialysis machines and vascular-access techniques should be different. For patients undergoing daily dialysis, it is particularly important to use the buttonhole method of needle insertion into the fistula with a single puncture, since there are fewer complications with this method, despite more frequent cannulations.8 (When this method is used, with repeated cannulation into the exact same puncture site, a scar-tissue tunnel tract develops that allows the needle to follow the same path to the blood vessel on each cannulation.) The authors did not provide information about whether this technique was used in one or both groups; if this method of fistula puncture was not used, that fact could explain the adverse results regarding vascular access in frequent-dialysis group.

This randomized, controlled trial, which took a decade to complete, did show that frequent dialysis was better with respect to control of hypertension and control of hyperphosphatemia. Furthermore, it was associated with favorable changes in the coprimary composite outcomes of death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Whether more frequent dialysis will become the standard of care is not yet evident. However, despite issues with suboptimal reimbursement, the number of patients undergoing daily hemodialysis has been slowly increasing.

This study confirms that more frequent hemodialysis confers certain advantages. Whether the more frequent vascular-access and clotting issues would be increasingly problematic over time is not known. Whether patients would do even better at home is also unclear.

source: NEJM