Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean ± SD eKt/V for patients randomized to these targets was 1.14 ± 0.11 and 1.52 ± 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 ± 0.11 and 1.50 ± 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The dialyzer mass transfer-area coefficient (KoA) for urea is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = ~5/model, total N = 107) in vitro at 37°C for three countercurrent blood (Qb) and dialysate (Qd) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea KoA values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea KoA was similar for each. Urea KoA did not change (690 ± 160 vs. 680 ± 140 ml/min, P = NS) when Qb increased from 306 ± 7 to 459 ± 10ml/min at a nominal Qd of 500ml/min. When Qd increased from 504 ± 6 to 819 ± 8ml/min at a nominal Qb of 450ml/min, however, urea KoA increased (P < 0.001) by 14 ± 7% (range 3 to 33%, depending on the dialyzer model) to 780 ± 150ml/min. These data demonstrate that increasing nominal Qd from 500 to 800ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in urea clearance than predicted assuming a constant KoA

Imprecision of the hemodialysis dose when measured directly from urea removal

Imprecision of the hemodialysis dose when measured directly from urea removal.BackgroundThe postdialysis blood urea nitrogen (BUN; Ct) is a pivotal parameter for assessing hemodialysis adequacy by conventional blood-side methods, but Ct is relatively unstable because of hemodialysis-induced disequilibrium. The uncertainty associated with this method is potentially reduced or eliminated by measuring urea removed on the dialysate side, a more direct approach that can determine adequacy from the fraction of urea removed and by substituting an estimate of the equilibrated postdialysis BUN (Ceq) for Ct. For a patient with a known urea volume (V), Ceq, the equilibrated Kt/V (eKt/V), and the solute removal index (SRI) can be calculated from the predialysis BUN (C0), total urea nitrogen removed (A), and V from simple mass balance calculations (dialysate/volume method). However, a theoretical error analysis showed that relatively small errors in A, C0, or V are magnified when SRI or eKt/V is calculated using this method, especially at higher eKt/V values (for example, if eKt/V = 1.4 per dialysis, a 7% dialysate collection error causes a 20% error in eKt/V).MethodsDuring three to four baseline dialyses in each of 39 patients enrolled in the pilot phase of the HEMO Study, “A” was measured using an instrument that sampled dialysate frequently (Biostat®), and V was calculated from A, C0, and Ceq (median CV for V = 5.6%). The mean V was then applied to the dialysate/volume method to estimate eKt/V and SRI during two to five subsequent dialyses per patient (comparison dialyses). The accuracy and precision of these estimates were assessed by comparing them with eKt/V and SRI derived from a direct measurement of Ceq drawn 30minutes after dialysis (reference method), from mathematical curve-fitting of sequential dialysate urea concentrations (dialysate curve-fit method), and from another blood-side method that estimates eKt/V from single pool Kt/V and the fractional rate of solute removal (rate method): eKt/V = spKt/V - 0.6 · K/V + 0.03.ResultsDuring 128 comparison dialyses, median absolute errors for calculated eKt/V compared with the reference method were 0.169, 0.061, and 0.071 for the dialysate/volume method, the rate method, and the dialysate curve-fitting method, respectively. The corresponding correlation coefficients were 0.47, 0.88, and 0.81. For SRI, median absolute errors were 0.044, 0.018, and 0.027, and the correlation coefficients were 0.54, 0.85, and 0.74 for the three methods.ConclusionsThe precision of eKt/V and SRI measurements was significantly lower for the dialysate/volume method compared with the blood-side methods. Inclusion of the dialysate curve analysis provided by the Biostat® restored precision to the dialysate method to a level comparable to that of the blood-side methods. New techniques employing dialysate urea analysis should include a concentration profile to avoid these inherent methodological errors and assure the accuracy of eKt/V and SRI