Multicompartment urea kinetics in well-dialyzed children

Abstract

Multicompartment urea kinetics in well-dialyzed children. mum delivered K d t/V of 1.2 [1]. Extrapolation from adult Background. We have reported catch-up growth with hemostudies may be problematic, as more appropriate pediatdialysis (HD) of approximately 15 hours/week. Without an ric outcome measures-such as growth, school perforequilibrated post-treatment blood urea nitrogen, the variablemance, or pubertal development-might lead to very volume single-pool (VVSP) model will not account for urea different conclusions as to the relative importance of rebound, inflating the estimated HD dose (K d t/V). A two-pool model (FVDP) predicts rebound, but requires fixed compartthe small molecular weight toxins for which urea is a ment volumes for the equations to be solvable in closed form, surrogate marker. Prior to the introduction of recombialso inflating K d t/V. nant human growth hormone (rhGH), the mean annual Methods. We developed an approximate perturbation soluloss in height standard-deviation score (⌬HSDS) in pretion (WKB method) to a variable volume, two-pool (VVDP) pubertal HD patients was Ϫ0.4 to Ϫ0.8 SD/year [2]. model. Estimated model parameters were compared with the results of equilibrated kinetic studies using measured clearance However, we have recently described normal growth K d (N ϭ 17). Once the model was validated, we re-analyzed rates, catch-up growth, and normal puberty with inten-292 kinetic studies from our earlier cohort, which was considsive nutritional support and HD clearance in prepubertal ered well-dialyzed on the basis of growth rates (N ϭ 12, mean patients treated without rhGH [3]. With a weekly treatannual change in height standard deviation score ϩ0.31, mean ment time of approximately 15 hours and a single-pool follow-up of 26 months). Results. For the VVSP, FVDP, and VVDP models, respecurea K d t/V of approximately 2.0, the mean annual tively, the mean errors were (1) K d t/V, 0.22 Ϯ 0.07, 0.29 Ϯ ⌬HSDS was Ͼϩ0.3 SD/year, and predicted final adult 0.17, 0.06 Ϯ 0.07 (ANOVA, P Ͻ 0.001); (2) urea distribution height fell generally within 2 SD of genetic potential.

Reassessing hemodialysis adequacy in children: the case for more

“…As in Marsenic et al [53], the Smye method produced a smaller mean error with a larger standard deviation, and the resulting limits of agreement are probably too wide for reliable estimation of equilibrated K d t/V. Both the rate equation (-0.03±0.06) and our VVDP model (0.06±0.07) furnished small mean errors and clinically satisfactory limits of agreement [48]. The VVDP also yielded improved estimates of urea distribution volume, urea generation rate and protein catabolism (an Add-In to Microsoft Excel implementing both the VVSP and VVDP models is freely available from the author).…”

“…Compared to the VVSP, it resulted in significantly (P<0.001) smaller estimates of K d (4.4± 0.8 ml/kg/min), K d t/V (1.76±0.33 treatment -1 , range 1. 34-2.40), and normalized protein catabolic rate (1.5±0.4 g/kg/day) [48]. In addition to clarifying the dialysis dose needed to sustain normal growth and development, these data again illustrate the increased dietary protein recommended for pediatric patients.…”

“…Typically, the equations describing this system require an assumption of fixed-compartment volumes to permit closed-form solutions (as formulae predicting urea concentration as a function of time and other model parameters) [20,47]. In children with significant interdialytic weight gain, this leads to errors comparable to those of the VVSP [48]. Writing specifically for pediatrics, Smye proposed an ingenious solution, using the fixed-volume, two-pool (FVDP) model to develop a prediction formula for the equilibrated, postrebound BUN, which is used with the VVSP model to calculate equilibrated K d t/V, PCR, etc.…”

“…Since the latter model predicts that overestimation of K d t/V will be aggravated by shorter dialysis time (T d ) and increased dialysis efficiency (K d /V), these authors also proposed the rate equation, a semiempiric estimate of the equilibrated K d t/V based on the standard single-pool result and T d [49,52]. Formal comparisons of these methods in children are relatively recent [48,53]. Unlike the Smye method, the rate equation requires only standard pre-and end-treatment BUN samples and provides more reliable estimates of equilibrated K d t/V.…”

“…This includes a realistic rebound phase, a consequence of dialysis-induced disequilibration between ECF (C e ) and ICF (C i ) urea concentrations. Standard pre-and end-treatment BUN samples suffice to estimate clinically important kinetic parameters [48], which permits reanalysis of previous single-pool studies to assist in the formulation of dialysis prescriptions for individual patients or on a unit-wide basis. Relative to the true equilibrated K d t/V, the errors associated with these various models are shown in Fig.…”