By Peter Laird, MD
The NEJM of medicine recently published an article on evidence of the long dialysis weekend associated with an increased risk of cardiac death. This is not new information, in fact, Dr. Carl Kjellstrand noted the "unphysiology" of thrice weekly, short dialysis back in 1975 (here). In his treatise nearly 40 years ago, Dr. Kjellstrand showed convincing data that the then newly adopted thrice weekly short dialysis schedule popularized by large dialysis organizations is harmful to patients. In a historical review by Dr. Blagg, Dr. Ing, Dr. Berry and Dr. Kjellstrand, the rational basis of more frequent hemodialysis is described in part due to the discoveries of unphysiology by Dr. Kjellstrand in the early 1970's:
The Rationale for More Frequent Hemodialysis – ‘Unphysiology’
In the early 1970s, Kjellstrand et al. [12, 13] investigated factors related the untoward effects of dialysis. They showed that large fluctuations in body weight, electrolytes, osmolality, and urea concentration were more important with respect to morbidity than concentrations of small uremic toxins or middle molecules. This led them to formulate the ‘unphysiology’ hypothesis which suggested that wide swings of solutes and fluids in the body were significant causes of morbidity in dialysis patients. Daily or continuous dialysis would more closely mimic the function of the native kidney by reducing the magnitude of solute and fluid oscillations and so would be expected to be superior to the usual intermittent dialysis regimens.
The debate over the long dialysis weekend is not a new argument at all. It is a forty year debate based not on clinical evidence in the end ananlysis but instead on the business of dialysis. The thrice weekly dialysis schedule came about through the need to spread limited resources to keep as many people alive as possible. There has never been a single randomized and controlled trial setting this "standard" schedule, it was a business and financial decision that holds dialysis patients in America today prisoners of these fatal long weekends. Yet, instead of discussing how we can change this situation, many bloggers and influential nephrologists are calling for more studies before we change anything.
Interdialysis interval and mortality - dangers of a long weekend?
The data provides a compelling reason to do an adequately powered randomised controlled trial examing the impact of dialysis frequency and duration on clinical outcomes - though the logistical and funding issues around such a trial would be challenging to say the least.
How bad is the long break for dialysis patients?
What's next?: Further research is NEEDED before wide-spread practice alteration is warranted particularly given the profound policy implications, but our patients deserve this now. Specifically, we must determine:
o Optimal dialysis scheduling
o Patient preferences regarding frequency and duration (i.e.... will they come??)
o Cost-effectivness analyses (will more frequent HD reduce morbidity and thus cost?)
Mortlity Increases After 2-Day Interdialytic Intervals
Despite the study's limitations, the authors conclude the results provide sufficient clinical rationale for conducting a controlled trial assessing how dialysis services are provided.
It is time for action instead of further studies. The issue of more frequent and longer duration hemodialysis is a settled body of literature dating back to the 1960's and includes the recent FHN randomized and controlled trial which is largely ignored. Daily dialyis is a better solution and when applied in the setting of the home, it becomes the most cost effective and clinically beneficial dialysis modality.
I am grateful for one more well done study, but I see no need for any delay in implementing more frequent hemodialysis. In the study in question from the NEJM, the most important statistic to consider is that 41% of the patients in this study died over a two year period of time. With more frequent hemodialysis and of longer duration, that number could have been reduced by more than 60% according to several observation studies. It is time to place wasted lives at a higher importance than maximizing profit margins for Fresenius, Davita and the other giants of the dialysis industry.
How quickly we forget that the Frequent Hemodialysis Network Trial came about by observational data suggesting higher mortality with thrice weekly hemodialysis back in the 1990's. Here we are nearly 20 years later and all that the dialysis pundits can state after a compelling study showing further evidence that the long dialysis weekend kills the patients that dialysis is meant to keep alive is a call to more studies. When will we wake up to the circle of death surrounding all of these studies that continue to propagate more government grants for further study yet never apply the findings to saving lives.
The definititive randomized and controlled trial of adequate power is an impossible request since it would involve over 5000 patients, a number equal to the number of home hemodialysis patients in America today.
High-Frequency Hemodialysis: Rationale for Randomized Clinical Trials
Given these uncertainties, we do not have sufficient data on the effects of daily and nocturnal hemodialysis to advocate for its widespread use and underwrite its cost. In 2001, Chertow (19) argued that a RCT of frequent hemodialysis was necessary to answer the fundamental questions of whether these treatments improve outcomes and, if so, by how much. He urged that the primary outcome of such a trial should be mortality alone or mortality combined with a major morbid event. . .
When these investigators considered study design, it became increasingly clear that a study that is powered to detect a mortality effect was not feasible at this time. We estimate that currently 55 centers in the United States and Canada are performing frequent hemodialysis five times per week or more. These centers are dialyzing a total of approximately 600 patients with high-frequency hemodialysis at home or in-center. Power analysis showed us that with 1 yr of follow-up, we would need to enroll >3500 patients in the daily study and >5000 in the nocturnal study to achieve 90% power to detect a relatively substantial 30% reduction in mortality.
Ten years after the calls for the FHN randomized and controlled trial, forty years after Dr. Kjellstrand's unphysiology reports and over firty years since Dr. Scribner urged America to save lives, we can progress no further than to call for more study. History will not look kindly on this part of our American history that gave us the highest mortality rate for dialysis patients in the developed world. It is time indeed to apply what we have already learned and stop the catch 22 debates on more frequent hemodialysis that only propagate further study and little or no corrective action.
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