The Role of Online Hemodiafiltration in Contemporary Kidney Care.

Replacement of kidney function by dialysis maintains the lives of millions of patients. Clinical results however are still unsatisfactory with mortality rates and complications well above the matched control population. This has led to a continuous quest for more effective dialysis techniques and new biomaterials. In the 1980s, the production of synthetic membranes with higher water permeability ( i.e ., high flux) leveraged the development of techniques, such as hemodiafiltration (HDF), with improved solute removal, thanks to combination of diffusion and convection. Efficacy trials have demonstrated the superiority of HDF over high-flux hemodialysis for solute removal, hemodynamic tolerance, and survival. Consequently, the technique gained traction in Europe and Asia. In these trials, a minimum target convection volume ( i.e ., fluid replaced) of 23 L per session adjusted to body surface area (BSA, i.e ., 23 L multiplied by ratio of individual BSA normalized by 1.73 m 2 ) was required to maximize the benefit of the therapy. In general, the replacement fluid is delivered in the postfilter site, and to attain this target of 23 L adjusted to BSA, blood flows must be ≥350 ml/min, requiring 14-15 Gauge needles or ≥14 French catheters to avoid excessive hemoconcentration and circuit pressure issues. In its early days, the replacement solution was provided with sterile bags (offline), making the therapy costly and cumbersome. Online (OL), i.e ., real-time preparation of ultrapure fluid for replacement, has become the key to reduce cost and complexity, while making the technique (OL-HDF) safe and convenient. In the United States, however, existing regulations and concerns about safety prevented approval for clinical use. In 2024, OL-HDF has received approval by the US Food and Drug Administration in the United States, and this opens new options and perspectives in the management of people living with kidney failure.