MILESTONEMid-dilution Hemodiafiltration International Randomized Prospective Study on Incident Patients Focused on Outcome

It is a matter of fact that in the last decades the Chronic Kidney Disease (CKD) population has widely changed. In Italy, for example, more than 50% of the incident dialysis patients are more than 70 year old, with diabetic and hypertension being the major underlying diseases; moreover a great percentage of the patients starts dialysis with a burden of at least 1-2 comorbidities [1]. Online hemodiafiltration (online HDF) has been recently associated with better patient survival in comparison with standard hemodialysis in two large trials [2,3]; the overall relative risk of mortality was found to be approximately 33% lower in patients treated with online HDF [2,3]. These impressive results were not obtained anyway on the whole population, but in a sub-group analysis. A strong correlation was found between the total convective volume obtained and the mortality risk reduction; HDF was found to be significantly better than standard hemodialysis when a total convective volume of 19-22 L/session (in 4 hours sessions of post-dilution HDF) was achieved. These results support the importance of the "adequate convective dose" concept in order to improve the patient outcomes especially in frail patients, as recently demonstrated by a large randomised control trial, the MPO study [4], comparing High Flux versus Low Flux dialysis in patients with plasma albumin levels equal to or less than 4 gr/dl ( as a marker of patient comorbidities) and, in a post hoc analysis, in diabetic patients [4]. Mid-dilution HDF is a variant of classical HDF combining simultaneous pre- and post.-dilution in order to maximise middle and large solutes removal. The MILESTONE study would aim to fully demonstrate for mid-dilution HDF the significant mortality risk reduction observed in the recent mentioned studies.