**6. Conclusions**

A unified scheme was proposed for the definitions of the adequacy indices on the basis of the reference values for: 1) normalization of removed solute mass to body solute mass (FSR), 2) cleared water volume to urea distribution volume (KT/V), and 3) solute generation rate to solute concentration in blood (ECC). The selection of the reference method can be done using respectively: peak (p), peak average (pa), time average (over the whole treatment cycle, ta) and treatment time average (over time of all dialysis sessions during the treatment cycle, trta) values of solute mass or concentration. It is not clear a priori which reference

r c ref K T V

*HD3x* p 4.15 0.14 0.45 0.60 1.94 pa 4.24 0.14 0.51 0.69 2.26 ta 4.34 0.14 0.75 1.00 3.38 trta 3.63 0.12 1.00 1.34 3.80 *HD6xd* p 5.85 0.14 0.45 0.57 2.69 pa 6.02 0.15 0.59 0.75 3.64 ta 6.04 0.15 0.78 1.00 4.85 trta 5.10 0.12 1.00 1.28 5.26 *HD6xn* p 9.82 0.14 0.34 0.44 3.42 pa 10.13 0.15 0.53 0.68 5.44 ta 10.07 0.15 0.78 1.00 7.95

trta 9.18 0.13 1.00 1.29 9.35

Table 4. Nondimensional parameters KT/Vref, residual KrTc/Vref, the ratio of treatment time average to reference urea concentration Ctrta/Cref, the ratio of time average to reference urea concentration Cta/Cref and fractional solute removal, FSR, equation (40), for conventional hemodialysis provided three times a week (HD3x), daily hemodialysis carried out six times

ECC and FSR were found to be equivalent descriptions of dialysis, if the same reference method (peak, peak average, time average, treatment time average) was used, as suggested by equation (39). The ratio of ECC and FSR was similar for all definitions, in contrast to

The change of solute mass in the body during dialysis is due to the generation minus removal, but, in general, one can not assume that the solute removal is equal to the generation during the cycle time (i.e. intra- plus inter-dialysis time), especially in acute renal failure, ARF, patients; thus, even the measurement of removed solute in spent dialysate or filtrate does not necessarily accurately reflect the generated mass. In such cases, the real solute generation rate needs to be estimated using computer simulations for specific patients and dialysis parameters by fitting the theoretical predictions to the solute concentration profile using equation (8) for simulation. The calculation of FSR and ECC should then be based on equations (38) and (36) as it was shown by Debowska et al. (Debowska et al., 2010).

A unified scheme was proposed for the definitions of the adequacy indices on the basis of the reference values for: 1) normalization of removed solute mass to body solute mass (FSR), 2) cleared water volume to urea distribution volume (KT/V), and 3) solute generation rate to solute concentration in blood (ECC). The selection of the reference method can be done using respectively: peak (p), peak average (pa), time average (over the whole treatment cycle, ta) and treatment time average (over time of all dialysis sessions during the treatment cycle, trta) values of solute mass or concentration. It is not clear a priori which reference

trta ref C C

ta ref C

<sup>C</sup> FSR

ref KT V

a week (HD6xd) and long, nocturnal hemodialysis (HD6xn).

**5. Adequacy indices for steady and non-steady metabolic state** 

much different values of the indices themselves.

**6. Conclusions** 

method should be used (ref = p, ref = pa, ref = ta or ref = trta) for the assessment of the treatment adequacy. To get a consistent scheme of definitions and relationships, the reference solute distribution volume was defined as Vref = Mb,ref / Cref. For each reference method, three adequacy indices, FSR, KT/V and ECC, can be defined. The computer simulations demonstrated that these indices are related, and that the relationships follow their definitions.

In general, ECC is equivalent to FSR, equation (39), if the same type of reference method is applied for both parameters (Debowska et al., 2005; Waniewski et al., 2006). The coefficient of proportionality, Vref/Tc, depends only slightly on the details of the procedure, especially on the schedule of water removal and the degree of total body water variation during the treatment cycle as well as the difference between urea concentrations in intracellular and extracellular compartments that may develop during dialysis sessions. Nevertheless, the variations of Vref between different definitions and procedures for the same patient are small. If a reference method (p, pa, ta, trta) of FSR and ECC definitions is fixed, then the changes in FSR are reflected by the changes in ECC and vice versa for the same patient. However, this relationship is different for patients with different total body water, which may also differ between patient populations.

One advantage of using equivalent continuous clearance, ECC, or fractional solute removal, FSR, is that these indices permit comparison of hemodialysis and peritoneal dialysis doses, and allow the addition of the contributions from HD, PD and residual renal function into the whole index for solute removal efficiency, and thus these indices could provide a basis for setting one standard target dose for all patients regardless of dialysis modality, frequency and duration (Depner, 2005; Debowska et al., 2007a). Note that ECC and FSR may also be successfully applied in continuous and semi-continuous therapies (e.g. continuous veno-venous hemofiltration, CVVH, slow low-efficiency daily dialysis, SLEDD) in patients with acute renal failure (Clark et al., 1999; Leypoldt et al., 2003; Debowska et al., 2010).

From the beginning of the era of dialysis treatment, there has been a quest for the optimal dialysis index. The history reflects the complexity of this matter, and attempts to simplify the meander way of this process that has not yet been finished because different versions of existing dialysis modalities are applied, new therapies are being introduced into clinical practices as new techniques become available. Compartmental models and solute kinetic analysis, presented here, used for the mathematical and computer-based description of delivered dose of dialysis are important tools for the evaluation of dialysis adequacy.

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Kinetic Modeling and Adequacy of Dialysis 25

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**2** 

*Canada*

**Automated Blood Volume Regulation**

Isabelle Chapdelaine, Clément Déziel and François Madore

Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), occurring in up to 20 to 33% of sessions (Daugirdas, 2001). IDH is responsible for various minor symptoms (nausea, vomiting, muscle cramps, dizziness, and fatigue) during dialysis, but is also associated with more severe adverse events such as myocardial infarction (Burton et al., 2009) and cerebral ischemia (Mizumasa et al., 2004). Moreover, as a result of frequent interruption of sessions and repetitive administration of intravenous fluids, underdialysis and inability to reach dry weight, with subsequent chronic overhydration, can follow. Traditionally, HD prescriptions are based on clinical evaluation and laboratory measurements, and are re-evaluated periodically or when an adverse event, such as hypotension, commands it. The drawback of this prescription is that it relies on previous observations, with the assumption that the same will hold true for the next sessions. Hence, it implies discomfort for the patients, as the actions to remediate to IDH, for example, by stopping ultrafiltration (UF) or adjusting dry weight, are taken on an *a posteriori* basis

In an attempt to prevent IDH, technological advances have made possible the detection of subclinical predictors of hemodynamic instability, for example relative blood volume variations. With repetitive measurement of such specific parameters during HD (Mercadal & Petitclerc, 2009), actions can be implemented to correct the monitored parameter toward a desired target, with the aim of preventing overt IDH. When this action is automatic and

In this chapter, we will review some of the physiological basis of IDH and blood volume reduction during HD, and we will examine the technical aspects of the various devices used to adjust blood volume during dialysis, with special emphasis on biofeedback systems. Finally, we will study the literature published on the effects of automated blood volume regulation devices on the occurrence of hypotensive episodes, volume overload control,

The causes of IDH are multifactorial. On one side, a number of patient-related conditions can promote blood pressure (BP) fall during HD: age, comorbidities such as diabetes and cardiomyopathy, anemia, large interdialytic weight gain (IDWG), use of anti-hypertensive

regulated by a closed feedback loop, it is called biofeedback.

hypertension management and quality of life in chronic HD patients.

**1. Introduction**

(Locatelli et al., 2005).

**2. Intradialytic hypotension**

**During Hemodialysis**

*Hôpital du Sacré-Coeur de Montréal, Montréal*

