**1. Introduction**

Conventional diffusion‐based dialysis modalities, namely, low‐flux and even high‐flux hemodialysis (HD), are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for chronic kidney disease (CKD) patients [1]. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broadrange of middle‐ and large‐size uremic toxins implicated in the pathophysiology of CKD [2, 3]. In addition, convective‐based modalities have been shown to improve hemodynamic stability [4, 5] and to reduce patients' inflammation profile—both factors implicated in CKD morbidity and mortality [6–8]. Growing clinical evidence indicates that HDF‐based modalities provide CKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it hasrecentlyemergedthattheclinicalbenefitsassociatedwithHDFarepositively associated with the total volume of fluid removed by ultrafiltration per session or per week [9– 12].This finding adds a new component to the conventionaldialysis adequacy concept,namely, convective dose.

In this chapter, we elucidate the concept of convective dose and discuss the threshold above which an improvement in CKD patient outcome can be expected. In addition, factors impli‐ cated in the achievement of an optimal convective dose in the sense of best clinical practice are reviewed and clinical evidence supporting the use of HDF today is summarized.

#### **1.1. Why is hemodiafiltration needed?**

From a nephrologist's perspective, it is disappointing to observe that outcomes of end‐stage kidney disease (ESKD) patients remain poor despite significant progress in hemodialyzer performances, HD machines and monitoring devices, better understanding of uremic toxicity, and improved patient management. Even without an in‐depth analysis of root causes and reasons for renal replacement therapy (RRT) limitations, several factors are easily recognizable as contributing to this outcome. It is usually convenient to group these into two categories: "nonmodifiable factors," such as age, gender, ethnicity, comorbidity profile, and kidney disease history, and "modifiable factors," such as RRT modality and treatment adequacy. Changing the renal replacement treatment paradigm and improving practice patterns to ensure customized and better care are the only ways to improve the outcomes of ESKD patients.

In this context, two main options are available. First, HDF is today's most innovative, prom‐ ising, and advanced alternative to high‐flux HD. By combining diffusive and enhanced convective solute mass transfer, HDF offers the most efficient RRT today over a wide spectrum of uremic toxins including middle‐ and large‐sized solutes. Using ultrapure dialysis fluids (water and dialysis fluid), HDF constitutes a highly biocompatible system and suppresses the occurrence of microinflammation processes [13–15]. By reducing the incidence of hypotensive episodes as well as dialysis intolerance symptoms [16–18], HDF may reduce or prevent repetitive cardiovascular insults and their deleterious long‐term consequences. By giving access to an unlimited amount of substitution fluid at the cost of ultrapure dialysis fluid, online HDF provides a cost‐effective approach for optimizing and customizing HDF treatment prescription to the patient's metabolic needs. Provided that best clinical practices and hygienic rules are applied, HDF offers a reliable, efficient, and cost‐effective RRT tool.

Second, the extension of treatment time is the more physiologic approach to improving patient outcome, even if not the most popular one. Increasing treatment time and/or frequency is the best way to facilitate sodium mass removal and thereby restore extracellular fluid volume, to ensure removal of uremic compounds with low intracorporeal mass transfer coefficients or tightly bound to albumin, and to minimize "nonphysiological" changes due to the aggressive nature of intermittent treatment schedules. These two approaches, HDF and extended treatment time, should not be considered competitive but rather complementary. Only a few studies have combined the solute mass transfer capacity of HDF with increased treatment time [19–21] and all clinical trials have confirmed the tremendous benefits of such combination on intermediary and long‐term outcomes.

#### **1.2. What is the clinical evidence for hemodiafiltration?**

**1. Introduction**

78 Advances in Hemodiafiltration

convective dose.

patients.

**1.1. Why is hemodiafiltration needed?**

Conventional diffusion‐based dialysis modalities, namely, low‐flux and even high‐flux hemodialysis (HD), are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for chronic kidney disease (CKD) patients [1]. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broadrange of middle‐ and large‐size uremic toxins implicated in the pathophysiology of CKD [2, 3]. In addition, convective‐based modalities have been shown to improve hemodynamic stability [4, 5] and to reduce patients' inflammation profile—both factors implicated in CKD morbidity and mortality [6–8]. Growing clinical evidence indicates that HDF‐based modalities provide CKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it hasrecentlyemergedthattheclinicalbenefitsassociatedwithHDFarepositively associated with the total volume of fluid removed by ultrafiltration per session or per week [9– 12].This finding adds a new component to the conventionaldialysis adequacy concept,namely,

In this chapter, we elucidate the concept of convective dose and discuss the threshold above which an improvement in CKD patient outcome can be expected. In addition, factors impli‐ cated in the achievement of an optimal convective dose in the sense of best clinical practice are

From a nephrologist's perspective, it is disappointing to observe that outcomes of end‐stage kidney disease (ESKD) patients remain poor despite significant progress in hemodialyzer performances, HD machines and monitoring devices, better understanding of uremic toxicity, and improved patient management. Even without an in‐depth analysis of root causes and reasons for renal replacement therapy (RRT) limitations, several factors are easily recognizable as contributing to this outcome. It is usually convenient to group these into two categories: "nonmodifiable factors," such as age, gender, ethnicity, comorbidity profile, and kidney disease history, and "modifiable factors," such as RRT modality and treatment adequacy. Changing the renal replacement treatment paradigm and improving practice patterns to ensure customized and better care are the only ways to improve the outcomes of ESKD

In this context, two main options are available. First, HDF is today's most innovative, prom‐ ising, and advanced alternative to high‐flux HD. By combining diffusive and enhanced convective solute mass transfer, HDF offers the most efficient RRT today over a wide spectrum of uremic toxins including middle‐ and large‐sized solutes. Using ultrapure dialysis fluids (water and dialysis fluid), HDF constitutes a highly biocompatible system and suppresses the occurrence of microinflammation processes [13–15]. By reducing the incidence of hypotensive episodes as well as dialysis intolerance symptoms [16–18], HDF may reduce or prevent repetitive cardiovascular insults and their deleterious long‐term consequences. By giving access to an unlimited amount of substitution fluid at the cost of ultrapure dialysis fluid, online HDF provides a cost‐effective approach for optimizing and customizing HDF treatment

reviewed and clinical evidence supporting the use of HDF today is summarized.

Although many studies associate HDF with significant improvements in ESKD patient outcomes, still some conflicting data or cost concerns have hampered general clinical and widespread acceptance of this method. Here, we attempt to reconcile facts and concerns regarding HDF. To begin, it should be stressed that a differentiated understanding of HDF should be adopted as opposed to considering HDF to be a generic term that covers all convection‐based renal replacement modalities. The differentiation necessary lies in the magnitude of the convection dose that must be delivered to improve outcomes of ESKD patients. Based on published literature and our own experience, we revisit the current definition of convective dose and its threshold value for improved patient outcome, we review the factors affecting convective dose delivery, we summarize the best clinical practices in HDF prescription, and we summarize the main studies addressing clinical outcomes.
