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Adequacy of Continuous Renal Replacement Therapy: Prescription and Delivery
Objectives
This chapter will:
- 1.
Help the reader understand the concept of clearance and the manner in which it is applied to estimate dose of renal replacement therapy.
- 2.
Describe the differences in the use of urea kinetic modeling (UKM) for end-stage renal disease and acute kidney injury.
- 3.
Help the reader understand the important studies that have employed urea kinetic approaches to quantify the dose of continuous renal replacement therapy (CRRT).
- 4.
Discuss the major studies that have assessed the relationship between CRRT dose and patient outcome.
- 5.
Explain the rationale for applying a continuous-equivalent UKM.
Measurement of delivered dialysis therapy is performed routinely in the management of patients with end-stage renal disease (ESRD), and urea-based quantification tools validated in prospective clinical trials are available to clinicians. On the other hand, the quantification of renal replacement delivery in acute kidney injury (AKI) is less established. Although the advent of continuous renal replacement therapy (CRRT) involved a focus on its hemodynamic benefits relative to conventional hemodialysis (HD), early kinetic studies employing adaptations of chronic dialysis approaches also demonstrated clear advantages for CRRT with respect to urea clearance and azotemia control. Additional kinetic comparisons also have indicated CRRT has advantages over HD for the removal of solutes over a broad molecular weight range. Although the greater solute clearance capabilities afforded by CRRT relative to intermittent therapies generally are recognized by clinicians, neither urea nor any other solute is employed specifically for CRRT dose assessments in clinical practice. Instead, the landmark trial performed by Ronco et al. has established effluent-based dosing as the standard of care for CRRT. Nevertheless, this parameter does not provide an accurate estimation of actual solute clearance and has created confusion among many clinicians, especially those familiar with urea-based dose measurements in the chronic dialysis setting. To address this problem, we reappraise dose prescription and delivery for CRRT and propose an adaptation of a chronic dialysis parameter (standard Kt/V) as a benchmark to supplement effluent-based dosing. (In this expression, which represents a normalized dose of dialysis, K is urea clearance, t is treatment time, and V is urea volume of distribution.) Before this, the key differences in the application of renal replacement therapy (RRT) quantification to the ESRD and AKI populations are discussed, and a comprehensive review of the literature regarding the application of these methodologies to CRRT is provided.
Use of Clearance to Quantify Dose in Renal Replacement Therapy
Overview of Clearance
The concept of solute clearance, integral to therapy dose in chronic dialysis, is defined as the ratio of mass removal rate (N) to blood concentration (C B ) :
When this equation is applied, a steady-state assumption typically is made, implying that net solute generation is balanced by net removal. For continuous depuration processes (e.g., endogenous kidney function), the indexing of mass removal rate to blood concentration allows for patients with widely varying kidney function to be compared with the same standard. Although not readily evident by inspection of Eq. 1 , the relationship between solute removal and clearance is therapy specific. This issue has been evaluated critically by several investigators, including Clark and Henderson. Assuming constant urea clearance, these investigators have demonstrated that although conventional HD's relatively high efficiency results in a high urea mass removal rate early in a treatment, this rate decreases substantially as the transmembrane concentration gradient for removal is dissipated as a result of falling blood concentrations ( Fig. 170.1A ). As such, cumulative solute removal begins to reach a plateau later in treatment, leading to a “self-defeating” situation for removal of small solutes eliminated efficiently. Fig. 170.1B demonstrates the same relationship between urea mass removal rate and instantaneous clearance for a CRRT filter operated at steady state (i.e., constant clearance and urea generation rate with a constant blood urea nitrogen (BUN) as a result). In this case, mass removal rate also remains constant, leading to a linear increase in cumulative solute removal over time. This comparison demonstrates the powerful effect of long treatment duration in CRRT, even though instantaneous clearance rates are relatively low.
Unified clearance expressions have been proposed to quantify solute removal by ESRD therapies ranging from conventional (thrice-weekly) HD to continuous therapies. These approaches include equivalent renal clearance, solute removal index, and standard urea clearance. In different ways, these methodologies attempt to incorporate intermittent effects on treatment efficiency and actual solute removal. As suggested above, the differences in solute removal rates early versus late during an intermittent treatment (despite constant clearance) do not allow direct comparison of Kt/V values derived, for example, from a 2-hour treatment and a 4-hour treatment. Likewise, direct comparison of the dose provided by intermittent and continuous therapies is not straightforward. Standard Kt/V is a “continuous-equivalent” methodology in which effective clearances provided by various intermittent schedules are referenced to a weekly continuous Kt/V provided by chronic peritoneal dialysis (PD). In this approach, pretreatment (peak) and steady-state BUN values for intermittent therapies and PD, respectively, are incorporated. Although the original application of standard Kt/V was in chronic dialysis, it is also suited to CRRT, as discussed subsequently.
Finally, dialysis quantification parameters other than clearance are also important to consider. Although clearance is a representation of treatment efficiency at a specific time or over a relatively limited time period, intensity can be defined as the product of clearance and cumulative treatment time. This parameter can be employed to demonstrate that despite relatively low solute clearance rates, cumulative solute removal with CRRT is typically much greater in comparison to more efficient therapies delivered intermittently. Finally, efficacy measures the effective removal of a specific solute resulting from a given treatment in a given patient. Efficacy can be defined numerically as the ratio of intensity to volume of distribution for a specific solute—as such, urea Kt/V is an efficacy parameter. A recent consensus publication regarding nomenclature used for acute RRT therapies reinforces these concepts.
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