Global Kidney Trials Insights: A Guide for Everyone

1. The question for investigation?

Do two different kinds of hemodialysis produce different outcomes in adult populations with kidney failure? The investigators examined deaths from any cause as outcomes of primary interest. “Outcome” refers to an event over time that is measured to monitor the impact of a treatment in a given population. The investigators were also interested in looking at death from heart and blood vessel diseases, and recurrent hospitalizations.

The two kinds of hemodialysis treatments were high flux hemodialysis (HD) and high dose hemodiafiltration (HDF), which use different methods to move substances across the dialysis filters to clean the blood.

In hemodialysis, wastes are removed from the blood by travelling through a barrier (called a membrane) in the filter of the dialysis machine, which allows wastes to pass through but aims to keep important parts of the blood, like blood cells and protein, in the bloodstream. One challenge of this approach is that some larger wastes (called middle-molecular-weight molecules), do not pass through the barrier very well. The build-up of these wastes may increase the risk of health problems, including for heart health. One alternative, called hemodiafiltration, is combining this process with direct fluid removal by adding many tiny holes, also called pores, to the membrane. These pores allow fluid and waste to be passed through more easily, including larger wastes that might not otherwise be removed through dialysis. As this process involves much more fluid being removed, some replacement waste-free fluid is added to the filtered blood before it returns to the body. It is unclear if this approach improves heart health and survival.

1360 people from across Europe were placed randomly on one of the two treatments for an average of over two years. All of them had already been receiving high flux HD for at least three months before the study started, and were randomized – like flipping a coin – to see which of the two dialysis treatments they would receive.

Compared to many populations of people receiving dialysis, the group in the study was younger (with average age of 62) and over 80% of them had an arteriovenous fistula (AVF), which is an irregular connection between an artery and a vein. Younger age and the presence of an AVF are important factors associated with better outcomes overall.

2. The findings of the study

People who received hemodiafiltration appeared to have a lower risk of deaths from any cause than the other group. Death rates were three % lower, meaning that out of every 100 people, three fewer people died while receiving hemodiafiltration. There were no differences in the other outcomes of interest, such as for death specifically from heart disease, or repeat hospitalisations. Additional information is to be expected about patient reported outcomes (how people felt), as well as costs.

These two aspects are important for policy makers and clinicians, since the procedure of hemodiafiltration is more expensive, uses more water and resources than hemodialysis, is not

available everywhere in the world, and we also want to know how well the patients like or tolerate the two treatments.

Overall, this is a well-done large study in a group of relatively young, well patients that supports the use of a more intensive form of dialysis, called hemodiafiltration.