Urea Distribution Volume Research Articles

A simple approach for assessing equilibrated Kt/V 2-M on a routine basis

Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods. An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula. Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26). The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required.

Insight: Effects of Reduced Intradialytic Urea Generation Rate and Residual Renal Clearance on Modeled Urea Distribution Volume and Kt/V in Conventional, Daily, and Nocturnal Dialysis

Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load. To determine the possible effects of reduced G or Kru during dialysis on the calculation of the volume of distribution (V) and Kt/Vurea, we modeled 3 and 6/week nocturnal, 6/week short daily, and 3/week conventional hemodialysis. A modified 2-pool mathematical model of urea mass balance with a constant time-averaged G was used, but the model was altered to allow adjustment of the ratio of dialytic/interdialytic G (Gd/Gid) and dialytic/total Kru (Krud/Kru) to vary from 1.0 down to near zero. In patients dialyzed six times per week for 400 minutes per session, when Gd/Gid was decreased from 1.0 to 0.05, the predicted urea reduction ratio (URR) increased from 68.9% to 80.2%. To achieve an increased URR of this magnitude under conditions of constant G (Gd/Gid=1.0) required a decrease in modeled urea volume (V) of 36%. At Gd/Gid ratios of 0.8 or 0.6 (corresponding to 20% or 40% reductions in intradialysis G), the modeled URR was increased to 71.0% or 73.3%, causing a 7% or 15% factitious decrease in V. The error was intermediate for the 3/week nocturnal schedule, and was much less pronounced for the 6/week daily and 3/week conventional treatments. Reductions in intradialytic Kru had the opposite effect, lowering the predicted URR and increasing the apparent V, but here the errors were of much lesser amplitude. The results suggest that, particularly for nocturnal dialysis, the standard "constant G" urea kinetic model may need to be modified.

Effect of treatment frequency on haemodialysis dose: comparison of EKR and stdKt/V

Haemodialysis outcome cannot be improved by increasing the dialysis session dose above the current standard in conventional schedules. Promising results have been reported from daily dialysis, but the optimal dose has not been established. Weekly eKt/V, equivalent renal clearance (EKR) and stdKt/V were compared retrospectively in 588 complete urea kinetic modelling sessions of 35 haemodialysis patients. Equivalent values of EKR and stdKt/V corresponding to the standard and high doses of the HEMO study were defined by computer simulation. The effect of frequency on the dose measures was demonstrated by simulating different schedules. EKR and stdKt/V take into consideration both frequency and RRF, but appreciate them differently. The values of EKRc (EKR in millilitres per minute, normalized to distribution volume 40 l), stdEKR (EKR in litres per week divided by urea distribution volume in litres) and stdKt/V corresponding to eKt/V 1.20-close to the standard dose in the HEMO study-were 13.2 ml/min/40 l, 3.34/wk and 2.23/wk, respectively. stdKt/V appreciates frequency more than EKR. A spreadsheet was created to compute the dialysis session time to achieve the EKR or stdKt/V target when the basic urea kinetic variables are known. Haemodialysis efficiency can be increased by increasing frequency. EKR and stdKt/V are more appropriate than weekly eKt/V as measures of dialysis dose in different schedules. With increasing frequency, stdKt/V as the dosing target results in shorter treatment times and higher concentrations than EKR.

A comparison of methods for determining urea distribution volume for routine use in on-line monitoring of haemodialysis adequacy

The availability of haemodialysis machines equipped with on-line clearance monitoring (OCM) allows frequent assessment of dialysis efficiency and adequacy without the need for blood samples. Accurate estimation of the urea distribution volume 'V' is required for Kt/V calculated from OCM to be consistent with conventional blood sample-based methods. Ten stable HD patients were monitored monthly for 6 months. Time-averaged OCM clearance (K(OCM)) and pre- and post-dialysis blood samples were collected at each monitored session. The second generation Daugirdas formula was used to calculate the single-pool variable volume Kt/V, (Kt/V)(D). Values of V to allow comparison between OCM and blood-based Kt/V were determined from Watson's formula (V(Watson)), bioimpedance spectroscopy (V(BIS)), classical urea kinetic modelling (V(UKM_C)) and a simple computation of V (V(UKM_S)) from the blood-based Kt/V and K(OCM)t. Comparison of K(OCM)t/V with (Kt/V)(D) shows that using V(Watson) leads to significant systematic underestimation of dialysis dose. K(OCM)t/V(BIS) agrees with (Kt/V)(D) to within +/- 10%. K(OCM)t/V(UKM_S) is, by definition, identical to (Kt/V)(D) when initially calculated. However, if a historical value of V is used, agreement between K(OCM)t/V and (Kt/V)(D) over 6 months varies by 5% for V(BIS) and 10% for V(UKM_S). When investigating the effect of different treatment strategies on dialysis efficiency, any estimate of V can be used provided it is constant, as K is the relevant parameter. When frequent supervision of actual dialysis dose is required, the greatest consistency between K(OCM)t/V and the reference, Kt/V(D), over time is achieved with V(BIS).

Disease Severity Adversely Affects Delivery of Dialysis in Acute Renal Failure

Background/Aims: Methods of intermittent hemodialysis (IHD) dose quantification in acute renal failure (ARF) are not well defined. This observational study was designed to evaluate the impact of disease activity on delivered single pool Kt/V_urea in ARF patients. Methods: 100 patients with severe ARF (acute intrinsic renal disease in 18 patients, nephrotoxic acute tubular necrosis in 38 patients, and septic ARF in 44 patients) were analyzed during four consecutive sessions of IHD, performed for 3.5–5 h every other day or daily. Target IHD dose was a single pool Kt/V_urea of 1.2 or more per dialysis session for all patients. Prescribed Kt/V_urea was calculated from desired dialyzer clearance (K), desired treatment time (t) and anthropometric estimates for urea distribution volume (V). The desired clearance (K) was estimated from prescribed blood flow rate and manufacturer’s charts of in vivo data obtained in maintenance dialysis patients. Delivered single pool Kt/V_urea was calculated using the Daugirdas equation. Results: None of the patients had prescription failure of the target dose. The delivered IHD doses were substantially lower than the prescribed Kt/V values, particularly in ARF patients with sepsis/septic shock. Stratification according to disease severity revealed that all patients with isolated ARF, but none with 3 or more organ failures and none who needed vasopressive support received the target dose. Conclusion: Prescription of target IHD dose by single pool Kt/V_urea resulted in suboptimal dialysis dose delivery in critically ill patients. Numerous patient-related and treatment-immanent factors acting in concert reduced the delivered dose.

Refining the Model of Urea Kinetics: Compartment Effects

A 70-year-old female with chronic congestive heart failure requires maintenance hemodialysis because of end-stage diabetic nephropathy. She is dialyzed on Monday, Wednesday, and Friday for 2 hours using a dialyzer with an average urea clearance of 250 ml/min. Dry weight is 50 kg. Predialysis blood urea nitrogen (BUN) on Wednesday is 50 mg/dl; postdialysis BUN is 15 mg/dl. A single-compartment, variable-volume model of urea kinetics revealed the following: 1.5 hours of dialysis are sufficient to maintain Kt/V at 1.1/dialysis; protein catabolism is 0.92 g/kg/day; her volume of urea distribution is 43% of body weight. Provided the blood access device and dialysis equipment are functioning properly and the blood specimens are drawn and measured correctly, are the model predictions valid?

Ionic dialysance and the assessment of Kt/V: the influence of different estimates of V on method agreement

Ionic dialysance was recently introduced as a means to assess Kt/V (K(ID)t/V). With this method, urea distribution volume (V) has to be estimated. The primary aim of the present study was to assess the agreement between equilibrated Kt/V assessed by urea kinetic modelling (eKt/V) with K(ID)t/V taking into account different estimates of V, and to assess the monthly variation in V. Secondly, the mechanisms behind the intra-treatment changes in ionic dialysance and inter-treatment variability of K(ID)t/V were assessed. Sixty-six patients were included. eKt/V was estimated using 30 min post-treatment sampling in the second generation Daugirdas equation. V was assessed by the formulae of Watson and Chertow (V(Watson); V(Chertow)), double-pool urea kinetic modelling (V(UKM)) and by ionic dialysance (V(IOD)) [Diascan; Hospal(R)]. The use of V(UKM) or V(IOD) instead of V(Watson) or V(Chertow) improved the relation between eKt/V and K(ID)t/V (both r = 0.93; P < 0.001 vs r = 0.84 and r = 0.81; P < 0.001). Mean values of eKt/V (1.19 +/- 0.21), K(ID)t/V(UKM) (1.19 +/- 0.30) and K(ID)t/V(IOD) (1.21 +/- 0.25) were comparable. Intra-class correlation coefficient of V(IOD) was 0.87 with a 1-month interval and <0.75 after 2 and 3 months. Intra-class correlation coefficient of V(DP) was 0.79 with a 1-month interval and <0.75 after 2 and 3 months. Inter-treatment variation in K(ID)t/V during six consecutive dialysis sessions was 6.1% +/- 0.6%. Changes in blood flow were the main determinant of variations in K(ID)t/V (P < 0.05). During treatment, ionic dialysance decreased by 12 +/- 13 ml/min (P < 0.001). The decline in blood volume was the major determinant of the intra-dialytic change in ionic dialysance (P < 0.05). The use of V(IOD) and V(UKM) results in better agreement between eKt/V and K(ID)t/V compared with anthropometric formulae. K(ID)t/V was comparable with eKt/V and thus lower than expected for a single-pool method. V(IOD) and V(UKM), should be assessed at least monthly. K(ID)t/V varies widely between consecutive dialysis sessions, mainly due to differences in blood flow. During treatment, ionic dialysance decreases, which is related to the relative decline in blood volume.

Unapređenje kvaliteta hemodijalize bolesnika sa velikom tjelesnom masom i površinom i velikim volumenom distribucije ureje

Unapređenje kvaliteta hemodijalize bolesnika sa velikom tjelesnom masom i površinom i velikim volumenom distribucije ureje

An Integrative Description of Dialysis Adequacy Indices for Different Treatment Modalities and Schedules of Dialysis

Dialysis adequacy indices that are applied for the evaluation of the efficiency of urea removal include fractional water volume cleared from urea during dialysis (KT T/V), fractional solute removal (FSR), and equivalent urea clearance (EKR). Using a constant-volume, one-compartment urea kinetic model for an anuric patient, the FSR and EKR are shown to depend on only three nondimensional parameters: (i) KT/V, where K is the dialyzer clearance for hemodialysis (HD) or peritoneal mass transport coefficient for peritoneal dialysis (PD), T is the time period of dialysis, and V is urea distribution volume; (ii) T/Tc, where Tc is the length of treatment cycle; and (iii) VD/V, where VD is the volume of dialysis fluid applied. In particular, analytical formulas for FSR and EKR, valid for HD as well as for PD, were derived as functions of these three parameters. Numerical simulations, performed using a two-compartment urea kinetic model, showed that the analytical formulas are valid also for the two-compartment model, except for short, highly effective HD, where the overestimation of FSR and EKR using the analytical formulas is however, not higher than 20 and 16%, respectively. KT T/V is equal to KT/V for HD and FSR for PD. Thus, our formulas provide an integrative description of the relationships between dialysis efficiency indices and operational dialysis parameters that is valid for all modalities and schedules of dialysis. They may be applied not only for standard HD and continuous ambulatory PD, but also for HD with circulating dialysis fluid or intermittent forms of PD.

Metabolic consequences of body size and body composition in hemodialysis patients

Small body mass index is associated with increased mortality in chronic hemodialysis patients. The reasons for this observation are unclear but may be related to body composition. This study aimed to investigate the body composition in chronic hemodialysis patients. The difference between body mass and the sum of muscle, bone, subcutaneous, and visceral adipose tissue masses, measured by whole body magnetic resonance imaging, was defined as the high metabolic rate compartment representing the visceral mass. Protein catabolic rate was calculated from urea kinetics. Forty chronic hemodialysis patients (mean age 54.7 years; 87.5% African Americans; 45% females) were studied. High metabolic rate compartment expressed in percent of body weight was inversely related to body weight (r=-0.475; P=0.002) and body mass index (r=-0.530; P<0.001). In a multiple linear regression model, protein catabolic rate was significantly correlated only with high metabolic rate compartment (r=0.616; P<0.001). Assuming that protein catabolic rate in addition to protein intake reflects urea and uremic toxin generation, it follows that high metabolic rate compartment is the major compartment involved in their generation. Consequently, uremic toxin production rate may be relatively higher in patients with low body weight and low body mass index as compared to their heavier counterparts. The poorer survival observed in smaller dialysis patients may be related to these relative differences.

Reduction in urea distribution volume over time in clinically stable dialysis patients

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

Do different haemodialysis regimen interfere with genomic damage in patients with end-stage-renal disease?

Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the reference methods were 0.61 and 24.8 mL/min, respectively, and not significantly different when determined by blood-based methods. A single-pool urea kinetic model adequately described intradialytic PUN profiles, indicating that SLED was associated with minimal urea disequilibrium. This was supported by the parity between hemodialyzer and whole-body urea clearances, and the mean postdialytic urea rebound of 4.1% (P = 0.13 versus zero). Additional prospective studies are needed in this setting to define the optimal method for dialysis quantification, targets for azotemic control, and optimal modality of renal replacement therapy. In conclusion, SLED delivers a high dose of dialysis with minimal associated urea disequilibrium and can be quantified by Kt/V, SRI, and EKR from blood-based methods using single-pool urea kinetic models. © 2002 by the National Kidney Foundation, Inc.

ON‐LINE CLEARANCE MONITORING FOR BLOOD ACCESS MANAGEMENT

On-line Clearance Monitoring (OCM) provides frequent and precise information about urea clearance values during haemodialysis. In the case of blood access recirculation, it is presumed that urea clearance values on OCM would be lower and suspect to blood access malfunction. In order to check the relation between significantly lower urea clearance values and blood access recirculation, the Kt value (Clearance x time/min) for fifteen patients on OCM, including the patients with a low Kt/V in spite of their small urea distribution volume (V) was observed. Average urea clearance was calculated indirectly using Kt value (Kt/time in minutes = average clearance ml/min) and blood access recirculation tests performed using slow/stop flow two-needle, three samples method (urea method). After comparison of the recirculation percentage to clearance value, positive correlation between high recirculation and clearance reduction was noted. OCM alongside detection of haemodialysis inefficiency is also a practical instrument for blood access management between regular monitoring. Lower OCM urea clearance values demonstrate a possible blood access problem that can be confirmed with another method. When an OCM urea clearance reading is decreased by more than 25%, undiscovered access recirculation can be suspected.

Dialysis dose as a determinant of adequacy

The intent-to-treat analyses of all patients in the HEMO trial suggested that increases in dose of dialysis as measured by urea Kt/V were of marginal or no benefit when dialysis was provided in a 3 times/wk schedule. The as-treated analysis in the HEMO trial pointed to markedly increased mortality when the delivered dose decreased even slightly below the targeted dose, evidence of a dose-targeting bias. The intent-to-treat HEMO study results suggested a potential interaction between sex and the dose-mortality relationship, and this also has been found in some cross-sectional studies, the cause of which remains unexplained. Whether dialysis dose should continue to be targeted based on urea distribution volume (V), or targeted to a body size measure that is a lower power of body weight (such as body surface area), remains an open question. The lack of benefit of increasing the dialysis dose in a 3 times/wk setting is more understandable if one looks at measures of equivalent continuous solute removal, such as the standard Kt/V. Differences in standard Kt/V in the 2 dose arms of the HEMO trial, for example, were only about 15%. Without going into removal of very large solutes (eg, beta-2-microglobulin), which is discussed elsewhere in this issue, or protein-bound uremic solutes, the only way to provide significantly more dialysis dose may be to move to more frequent dialysis schedules and/or to very long session lengths. Here, benefit may be related as much to better control of salt and water balance as to better removal of uremic toxins.

Measurement of dialyzer clearance, dialysis time, and body size: Death risk relationships among patients

Urea pharmacokinetic equation systems have contributed to better understanding of treatment dose among hemodialysis patients. The methods are indirect, however, and require the measurement of blood urea nitrogen (BUN) concentration before and after a dialysis session to estimate the total treatment dose that clinicians prescribe [urea clearance x dialysis time (Kt)] indexed to an estimate of body size [the volume of urea distribution in the body (V)] yielding the ratio, Kt/V. New technology permits direct on-line measurement of average small molecule clearance (Kecn) during each dialysis treatment that can be multiplied by time (t) to give a direct measurement of total treatment dose (Kt). This study evaluated the relationship of measured Kt with death risk. It also evaluated the relationship of simple body size measures to risk and also the combination of one such measure [body surface area (BSA)] with Kt to death risk. The data were taken from the Fresenius Medical Care (NA) (FMCNA) clinical database that included patients who had outcome data, height and weight measurements, and at least one average Kecn and t measurement during April 2002. Kecn, t, and the body size measures [body weight, body mass index (BMI), and BSA)] were averaged during the month. Those values were used as predictors of survival during the next 1 year in unadjusted and case mix adjusted proportional hazards (Cox) models. Increasing values of Kecn, t, Kt and all of the body size measures were associated with lower death risk. The body size measure most closely associated with risk was the BSA that was used in subsequent models. Kt and BSA were independent risk predictors. There was a significant interaction between Kt and BSA in the case mix but not the unadjusted model indicating that the risk burden of lower total dialysis dose, Kt, may be greater among small than large patients. The direct measurement of dialysis dose during each treatment is practical and the values reported by it are clinically relevant. Higher dose was associated with better survival in both small and large patients treated three times weekly. Furthermore, smaller patients may require proportionately greater total dose than larger patients to achieve comparable survival.

Dose of dialysis: Key lessons from major observational studies and clinical trials

Dose of dialysis: Key lessons from major observational studies and clinical trials

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients

An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied. V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001). Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.

Simulation of post-dialysis urea rebound using regional flow model.

A regional flow model (RFM) can establish the missing link between hemodynamics and solute removal. We tried to simulate post-dialysis urea rebound using a RFM for the purpose of evaluating the validity of this model. Eight patients on maintenance hemodialysis with negligible renal function were investigated. The parameters of the RFM were estimated so as to fit the calculated values of urea nitrogen to the measured values during a dialysis session. The estimated parameters were total urea distribution volume (TUV), systemic blood flow (Qsys), flow fraction (fQH) and volume fraction (fVH) of the high-flow system. Thirteen types of parameter sets were used for the estimation. The urea rebound at 60 min after a dialysis session (Creb) and the rebound ratio (RR) were calculated using these estimated parameters. The accuracy of the calculated Creb and RR was assessed. The accuracy of Creb and RR determined using estimated TUV, by taking Qsys as systemic blood flow calculated from ultrasonic echo cardiogram (Qucg), fQH as 0.8, and fVH as 0.2, was insufficient (method 1a). The accuracy of these values was significantly increased by taking fQH as 0.85 (method 1b). The estimation of Qsys with TUV did not improve the accuracy of Creb and RR (methods 2a and 2b). The estimation of fQH, fVH, and TUV (method 8) increased the accuracy of Creb and RR significantly compared with method 1a, but not compared with method 1b. Even with method 1b or method 8, the percentage RR was less than 90% in two patients. By taking fQH as 0.85, an acceptably accurate simulation of urea rebound can be accomplished with the necessity to estimate only TUV. The simulation was not significantly improved by the estimation of Qsys, fQH, and fVH. The RFM is useful in practice, although it has some limitations.

Simple and accurate quantification of dialysis in acute renal failure patients during either urea non-steady state or treatment with irregular or continuous schedules.

The quantification of dialysis in critically ill acute renal failure (ARF) patients requires a unifying expression that can establish kinetic equivalence amongst patients treated with irregular or frequent intermittent haemodialysis (IHD) schedules or with differing renal replacement therapies. EKRjc is a generalized form of the equivalent urea renal clearance (EKRc), and represents the equivalent continuous urea clearance that will result in the given time-averaged concentration of urea, for the given amount of urea removal. The suitability of EKRjc for the measurement of dialysis dose in this setting is examined. 420 weeks of renal replacement therapy (IHD and continuous renal replacement therapy) were simulated in 15 virtual 'patients' using a variable volume double pool urea kinetic model. Additional data from eight ARF patients were used to exemplify calculations. 1260 EKRjc values were calculated using both formal urea kinetic modelling, as well as a simplified method that requires input of changes in patient fluid state and blood urea nitrogen concentrations over a period of observation, in addition to an initial estimate of patient post-dialysis urea distribution volume (V(T)). EKRjc is shown to provide a unifying expression of dialysis dose irrespective of IHD schedule or renal replacement therapy. EKRjc is shown to be independent from the assumption of the urea steady state, and intrinsically normalized to patient urea distribution volume to allow dose comparisons between patients of different size. Residual renal urea clearance is easily incorporated where present. EKRjc is easily calculated using the simplified method without the need for iterative urea kinetic modelling. The accuracy of this simplified method is maintained when the initial estimation of V(T) is both 25% greater or smaller than the true value. Calculation of EKRjc is exemplified using the clinical data. EKRjc is the most suitable urea kinetic expression for the quantification of dialysis in critically ill ARF patients.

Determination of urea distribution volume for Kt/V assessed by conductivity monitoring

Kt/V can be calculated continuously during dialysis without blood samples using the ionic dialysance method. Unlike the usual method using blood samples, a precise value for the patients' urea distribution volume is required. This study compared different methods for the determination of urea distribution volume (V) to evaluate their use in Kt/V measurement, based on conductivity monitoring. Ten patients were studied during 40 dialysis sessions. Total body water and V were determined using bioimpedance spectroscopy (BIS), anthropometric data, and blood-based kinetic data. Ionic dialysance was measured by conductivity monitoring. Total body water measured by bioimpedance was determined as VBIS= 37.0 +/- 7.1 L or 49.6 +/- 4.4% of body weight. V determined using ionic dialysance as input to urea kinetic modeling (UKM) was found to correlate well with total body water (VKecn= 36.4 +/- 5.2 L). All anthropometric equations overestimated measured V: VWatson= 40.7 +/- 3.9 L, VHume= 41.8 +/- 2.5 L, VChertow= 44.6 +/- 3.3 L, and VChumlea= 43.1 +/- 2.9 L. Single-pool Kt/V obtained by kinetic modeling was used as reference (Kt/V)SPVV= 1.49 +/- 0.15. Using different Vs as the V component in the ionic dialysance Kt/V, we obtained: Kecn*t/VWatson= 1.34 +/- 0.12, Kecn*t/VBIS= 1.51 +/- 0.21 and Kecn*t/VKecn= 1.52 +/- 0.18. The single-pool Kt/V calculated using the ionic dialysance method agreed with the conventional blood sample method provided that V was calculated using BIS or urea kinetics. V by either method was reproducible and varied little in an individual patient. Monthly determination of V allows determination of Kt/V for each dialysis session by ionic dialysance.