To what extent does high dose hemodiafiltration compared to high flux hemodialysis reduce risk of death in end stage kidney disease patients

End stage kidney disease ranks among the most severe chronic non-communicable diseases with an unmet medical need, given the high (between 10 and 15%) and stable annual mortality rates. Kidney replacement therapy is necessary when kidney function is below 10% of the normal value. Much effort is put into developing strategies to prevent chronic kidney disease progression. Regenerative medicine still is in the experimental phase and kidney transplantation is only available for a small number of patients. Indeed, the everyday reality is the growing number of dialysis patients. Haemodialysis treatment is the current standard of care for the vast majority of patients with end stage kidney disease. It is a substantial burden to the patient and for society. Haemodialysis treatment is associated with high risks for fatal and non-fatal cardiovascular disease, for infections, hospitalisation and low quality of life. Improvement in the currently available standard is urgently needed. Over the past decade an alternative for haemodialysis became available, i.e. haemodiafiltration. Both are accepted by regulatory authorities. Haemodiafiltration removes waste products that are accumulated due to kidney failure, more effectively than standard haemodialysis. Present evidence supports the idea of superiority of haemodialfiltration compared to standard haemodialysis. However, definite proof is lacking and as a consequence haemodiafiltration is not yet widely applied. This consortium aims to determine the best possible dialysis treatment by comparing the conventional guideline based haemodialysis treatment versus high-dose haemodiafiltration by carrying out a prospective randomized controlled clinical trial addressing clinical endpoints, quality of life and a cost-utility analysis. The study will deliver an answer on the question which intervention gives the best value for money. Therefore, it will be considered a “land mark” study, allowing publishing an “end of discussion” paper.

End stage kidney disease (ESKD) ranks among the most severe chronic non-communicable diseases with an unmet medical need, given the high (between 10% and 20%) and stable annual mortality rates in ESKD patients treated with dialysis. Kidney replacement therapy is necessary when kidney function is below roughly 10% of the normal value. Much effort is put into developing strategies to prevent chronic kidney disease progression. Regenerative medicine is still in the experimental phase and kidney transplantation is only available for a small number of patients. Indeed, the everyday reality is the growing number of dialysis patients. Haemodialysis (HD) treatment is the current standard of care for the vast majority of patients with ESKD. HD is associated with high risks of fatal and non-fatal cardiovascular disease, for infections, hospitalisation and low quality of life. Improvement in the currently available standard is urgently needed.



Over the past decade, an alternative for haemodialysis became available; called haemodiafiltration (HDF). HD and HDF are accepted by regulatory authorities. HDF removes waste products that are accumulated due to kidney failure, more effectively than standard HD. A individual patient-level data meta-analysis of four recent European randomised controlled trials, which comprised 2753 patients with a median follow up of 2.5 years was recently reported. The results indicate an approximate 22% reduction of mortality risk when convection volume dosages of < 23 L/session, standardised for Body Surface Area (BSA), were used. The main beneficial effect was demonstrated by an observed 30% reduction of cardiovascular mortality and specifically cardiac mortality. Importantly, the pooled analysis also suggested a 31% reduction in sudden death rate of borderline significance. A recent large observational study supports the notion that increased clinical benefit is related to higher dosages. Despite these recent findings, the scientific community remains critical, largely due to results that the beneficial effects might be explained by patient selection (i.e. a healthier patient receives more convection volume). Furthermore, the mechanism(s) of a possible beneficial effect is/are unproven. This also reduces the acceptance of the idea of superiority of HDF.



This consortium aims to determine the best possible dialysis treatment by comparing high-dose HDF versus conventional high-flux HD treatment by carrying out a international, multi-centre, prospective, randomised, controlled clinical trial addressing clinical endpoints, quality of life and a cost-utility. The CONVINCE study will deliver an answer on the question which intervention gives the best value for money. Therefore, it will be considered landmark study, allowing to publish an end of discussion paper.

Assessments will occur at

Month -1

Month 0

Month 3

Month 6

Month 9

Month 12

Month 15

Month 18

Month 21

Month 24

Month 27 (for part of the participants)

Month 30 (for part of the participants)

Month 33 (for part of the participants)

Month 36 (for part of the participants)

Usual care: Participants with ESKD who will be included will receive high-flux haemodialysis before randomisation. High-flux HD is defined as HD using high-flux dialysis membranes and bicarbonate based dialysate. This will be continued when randomised to usual care.



Intervention care: High dose HDF is defined as high dose HDF with online production of substitution fluid/dialysate according to manufacturer instructions. Substitution fluid is infused in the post-dilution mode. In case of different substitution modality (pre, mid or mixed dilution) a correction factor (resp. 2 times higher ¨C 1,5 times higher than in post dilution) will be applied to match the performance as detailed in Appendix I. High dose HDF is defined as a convection volume of ¡Ý 23 L (range +/- 1) adjusted to BSA/session.