Page 698 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Hemodialysis and Extracorporeal Blood Purification 685

is due to a combination of relative long treatment time Kt/V has become the international reference for dialysis
and relatively smaller patient size (5 to 40 kg) compared dosing and delivery. 76
with humans in which a URR target is 60% to 65%. This assessment of dialysis dose and intensity advances
In very large animals (50 to 70 kg), this degree of our understanding of the delivery of dialysis during indi-
treatment intensity is often difficult to obtain, and a vidual treatments but requires the additional measure-
URR of 80% to 85% is typical. ment of K d (Appendix, Equation 5) and the imprecise
Reduction ratios are convenient for clinical assessment estimation of V from the patients weight and hydration
but do not account for all aspects of solute transfer. Ure- status. These predictions of dialysis dose are limited by
mic toxicity and patient well-being are not predicted nec- simplifying assumptions regarding urea generation, fluid
essarily by the highest or lowest concentration or the removal, and solute transference during the session,
intermittent change of specific retained uremia solutes. 65 which require more extensive evaluation. A more funda-
The integrated exposure to uremia toxins over time is mental understanding and precise description of solute
considered by some a more realistic determinant of dynamics during dialysis can be derived from kinetic
well-being and therapeutic adequacy. 63,104,106,115,143 modeling of the intradialytic and interdialytic changes
For urea, this is expressed as the time-averaged concen- in BUN similar to pharmacokinetic profiles used
tration (TAC urea ), which is calculated as the area under to describe drug metabolism. 48,64,141 Urea kinetic
the BUN profile (curve) divided by the duration of the modeling (UKM) is fundamental to understanding the
dialysis cycle (Figure 29-1; Appendix, Equation 1). prescription, monitoring, and quality assurance of hemo-
TAC urea has been shown to predict morbidity and out- dialysis procedures and must be familiar to all
come in human patients undergoing hemodialysis and practitioners of this therapeutic modality. It dissects the
provides an integrated overview of urea dynamics (and mutually independent influences of dialysis, residual renal
presumably uremia toxicity) during a single or over function, nutrition, catabolism, and distribution volume
multiple dialysis cycles. It has been highly predictive of on the intermittent perturbations in urea concentration
dialysis adequacy and outcome for survival but remains during and between the dialysis sessions. This kinetic
nonspecific and fails to distinguish the multifactorial approach to urea metabolism also yields the fractional
contributions to urea metabolism during the dialysis clearance of urea (Kt/V) as a measure of dose in addition
cycle, including dialysis dose, urea generation, nutritional to urea generation rate (G), protein catabolic rate (PCR),
adequacy, residual clearance, and distribution and the distribution volume of urea (V) that are ionic
volume. 48,98,104,107,120 dialysance otherwise beyond clinical assessment.
At face value, neither predialysis BUN nor TAC urea are The simplest kinetic assessment of urea during inter-
adequate surrogates to characterize the adequacy of mittent hemodialysis is represented by a single-pool,
dialytic therapy or urea metabolism. An animal with a fixed-volume model, in which the entire volume of distri-
low predialysis BUN can represent effective dialysis (high bution of urea (i.e., total body water) is presumed to
dialysis delivery), recovering renal function (increased behave as a single pool with no change in volume or urea
residual renal clearance), inadequate nutrition (low urea input during the treatments (see Figure 29-1). 47,48,141–
generation rate or PCR), or volume overload (expanded 143 In this simplified model, the only kinetic variable is
urea distribution volume). Conversely, under dialysis, total urea clearance (K), which represents the sum of
worsening renal function, high catabolic rate, or volume residual renal clearance (K r ) and the clearance of the dia-
contraction can all be reflected by a high predialysis BUN. lyzer (Kd) (see Figure 29-1; Appendix, Equations 5 and
The dose of dialysis delivered to the patient can be 6). 186 The absolute removal of urea in this system will be
defined alternatively by the amount of clearance provided reflected by the change in urea concentration at any time
by the hemodialyzer during the dialysis session. Using the during dialysis such that:
measured (instantaneous) clearance of the dialyzer for
urea (K d , mL/min) and the dialysis session length (T d , C t ¼ C 0 e Kt=V , ð1Þ
minutes), the dose of dialysis can be defined as K d T d
or the volume of the patient cleared of urea (depurated where C t is the urea concentration at time ¼ t; C 0 is the
volume) during the treatment (mL). This value can be predialysis urea concentration at t ¼ 0; K is the total urea
indexed further to the total reservoir or distribution clearance; and V is the volume of urea distribution.
volume of urea in the patient (V, mL) to compare treat- Rearrangement of Equation 1 provides Equation 2 for
ment efficacy among patients of different body sizes as single-pool (sp) conditions,
V is equal to the patient’s total body water. This expres-
sion is analogous to conventional dosing of drugs as sp Kt=V ¼ lnðC 0 =C t Þ: ð2Þ
milligrams per kilogram of body weight. The value
obtained with this kinetic expression, Kt/V, (Appendix, Equation 2 is the fundamental kinetic expression for the
Equation 11) is unitless and represents the fractional fractional clearance of urea (dialysis dose) during a single
clearance of the urea distribution volume. 48,50,64,157,172 dialysis session. In the simplified single-pool model,