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