Urea Distribution Volume Research Articles

Modeling the Postdialysis Rebound

Three approaches are currently used in kinetic models (UKMs) to account for the postdialysis rebound in urea concentration, and thereby accurately measure the hemodialysis dose, KT/V (where K, T, V denote dialyzer clearance, dialysis duration, and urea distribution volume, respectively). The approach developed by Smye uses an intradialytic sample to predict the postdialysis equilibrium concentration, Ce, which is then used in a single pool UKM to give KT/V. A second approach developed by Tattersall introduces a patient clearance time, tp. The true dialysis dose is then given by T/(T + tp) x apparent dose, and tp is estimated to be 36 minutes. The Daugirdas analysis uses an empiric regression equation to give the true dose; KT/V)true from the single pool value, KT/V)sp; KT/V)true = KT/V)sp - (36/T)(KT/V)sp + 0.03. The analysis confirms the equivalence of all three formulas, which arises from the observation that during the later stages of dialysis, the urea concentration decreases as a single exponential. The formulas are independent of whether a flow or diffusion model is used to describe the kinetics of urea removal. The original analysis assumed constant volumes, but the effect of ultrafiltration volume u on C(e) may be accounted for by multiplying by (1 + u/V). The Smye equation is more vulnerable to error in practice, because small errors in the intradialytic sample give larger errors in the equilibrium concentration estimate, whereas dose estimates based on the Tattersall and Daugirdas equations are less affected by sampling errors. However, unlike the Smye approach, these two formulas would need adaptation for use with other solutes. The advent of continuous urea monitoring should permit more accurate, prospective estimates of equilibrium concentrations and dialysis dose.

Assessing dialysis adequacy and dietary intake in the individual hemodialysis patient

Urea kinetic modeling (UKM) and food records are widely used to assess the dialysis adequacy. Clinicians use these methods in individual patients to decide whether the dialysis prescription should be adjusted. We determined the variation in UKM parameters and dietary intake within individual patients in order to determine the required number of UKM measurements, and the number of food recording days to assess dialysis adequacy and dietary intake reliably. Session-to-session variation in urea reduction ratio (URR), Kt/V, urea distribution volume (UDVDDQ), and protein catabolic rate (PCR) was determined during three mid-week dialysis sessions in 50 stable hemodialysis patients on three-times per week hemodialysis with a Kt/V of 0.98 +/- 0.13 (mean +/- SD). The dialysis prescription was kept constant. The day-to-day variation in dietary protein intake (DPI) and dietary energy intake (DEI) was determined from seven-day food records. The 90th percentile value of the coefficient of variation (CV) was used to determine the number of measurements. The variation in URR [CV, 2.4% (0.3 to 9.5) median (range)] and in Kt/V [CV, 4.0% (0.6 to 11.6)] was small in the majority of the patients. The variation in UDVDDQ [CV, 4.9% (0.3 to 25.7)] and PCR [CV, 9.3% (0.8 to 28.5)] was considerably larger. The variation in DPI [CV, 17.3% (8.4 to 64.0)] was larger than that in DEI [CV, 12.9% (5.0 to 33.0)]. To assess the URR within +/- 10% of its true value, the average of two measurements was required. Reliable assessment of Kt/V required three measurements. URR and Kt/V could be assessed reliably from a single measurement in 86 and 66% of the patients, but we were not able to distinguish these patients beforehand. Reliable estimation of UDVDDQ required six measurements. The required number of measurements for PCR, DPI, and DEI was determined using a precision of +/- 20%. To assess PCR reliably, three measurements were needed. Estimation of DPI and DEI required seven and five food recording days, respectively. The session-to-session variation in URR and Kt/V is small in stable hemodialysis patients. Nevertheless, the averaged value of two to three measurements is required to assess the dose of dialysis reliably. Assessment of dietary intake requires at least three PCR measurements or food records for at least one week. Basing clinical decisions on a single dialysis adequacy assessment is an unjustified practice that should be abandoned.

Gender-specific differences in dialysis quality (Kt/V): 'big men' are at risk of inadequate haemodialysis treatment.

Inadequate dialysis dose is closely related to mortality and morbidity of maintenance haemodialysis (MHD) patients. According to the DOQI guidelines a minimum prescribed dialysis dose of single-pool Kt/V (Kt/Vsp)=1.3, equivalent to equilibrated double pool Kt/V (e-Kt/Vdp)=1.1, is recommended. Knowledge of patient-related risk factors for inadequate delivery of hacmodialysis would be helpful to select patient subgroups for intensive control ofdialysis adequacy. A retrospective survey was conducted to assess the prevalence of inadequate dialysis dose according to DOQI criteria during a 7-month period. A total of 320 e-Kt/Vdp measurements in 62 MHD patients were evaluated (mean effective dialysis time 222+/-32 min). Residual renal function (RRF) was expressed as renal weekly Kt/V (r-Kt/Vweek) and included into assessment of total weekly renal and dialytic Kt/V (t-Kt/Vweek). Inadequacy (e-Kt/Vdp<1.10) was prevalent in 37.2% of all measurements and in 22/62 patients (35.5%). In 54% of underdialysed patients r-Kt/Vweek compensated for insufficient dialytic urea removal. Mean weekly Kt/V was inadequate (t-Kt/Vweek<3.30) in 12/62 patients (19.4%) of whom 91.7% (11/12) were male. Body-weight, urea distribution volume (UDV). and body-surface area (BSA) were significantly higher in inadequately is adequately dialysed males. UDV>42.0 litres or BSA>2.0 m2 and a lack of RRF (r-Kt/Vweek<0.3) put 'big men' at increased risk to receive an inadequate dose of dialysis. Our data identify patients at risk for inadequate haemodialysis treatment. Special attention should be focused on 'big men' with UDV>42.0 litres or BSA>2.0 m2. In this subset of patients frequent measurements of t-Kt/Vweek and assessment of RRF should be mandatory.

Evaluation of Pre- and Postdilutional On-Line Hemodiafiltration Adequacy by Partial Dialysate Quantification and On-Line Urea Monitor

On-line highflux hemodiafiltration (HDF) is a clinically interesting and effective mode of renal replacement therapy, which offers the possibility to obtain an increased removal of both small and large solutes. The fundamental role of urea kinetic monitoring to assess dialysis adequacy in conventional hemodialysis has been widely studied. Both direct measurement of the urea removed by the modified direct dialysate quantitation (mDDQ) based on partial dialysate collection (PDC) and dialysate-based urea kinetic modeling (DUKM) using urea monitor have been advocated. The validity of this assessment tool in the patients with on-line HDF remained unclear. The aims of this investigation were (1) to compare the delivered Kt/V, urea mass removal (UMR), solute removal index (SRI) and normalized protein catabolic rate (nPCR) between pre- and postdilutional high-flux HDF; (2) to verify and compare the efficiency of pre- and postdilutional HDF using DUKM with on-line dialysate urea sensor, and mDDQ with partial dialysate collection. During both mode of HDF, the paired analysis urea removed and Kt/V showed no significant difference. Using mDDQ, mean values for predilutional mode were as follows: Kt/V 1.53 ± 0.01 UMR, 16.8 ± 0.3 g/session; urea clearance 178 ± 18 ml/min; SRI 75.5 ± 7.7%; urea distribution volume (V) 28.3 ± 1.2 liters; nPCR 1.34 ± 0.18 g/kg/day; on the other hand, mean values for postdilutional mode were Kt/V 1.58 ± 0.01; UMR 17.10 ± 0.28 g/session; urea clearance 184 ± 21 ml/min; SRI 77.2 ± 3.5%; urea distribution volume, 27.8 ± 1.5 liters; nPCR 1.34 ± 0.19 g/kg/day. The mean value of urea generation rate was 5.82 ± 1.12 mg/min during HDF. Our results showed that dialysis adequacy was achieved with both high-volume predilutional HDF and postdilutional HDF. These two modes of HDF provided similar and adequate small solute clearance. In addition, we found that on-line analysis of urea kinetics is a reliable tool for quantifying and assuring delivery of adequate dialysis.

Measurement of Hemodialysis Adequacy in a Changing World

Defining adequacy of dialysis remains an elusive goal. The application of the Kt/Vurea concept to clinical dialysis was a major improvement in trying to define a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of dialysis, divided by the patient's urea distribution volume (V) ought to give the best number to compare the efficiency of dialyses that patients receive. There are, however, many pitfalls associated with the whole Kt/Vurea concept.

Measurement of Hemodialysis Adequacy in a Changing World.

Defining adequacy of dialysis remains an elusive goal. The application of the Kt/Vurea concept to clinical dialysis was a major improvement in trying to define a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of dialysis, divided by the patient's urea distribution volume (V) ought to give the best number to compare the efficiency of dialyses that patients receive. There are, however, many pitfalls associated with the whole Kt/Vurea concept.

Whole body Kt/V from dialysate urea measurements during hemodialysis.

A new method for the calculation of dialysis dose from continuous measurements of dialysate urea concentrations has been developed. It is based on urea mass in the patient instead of plasma concentrations, and results in a measure of dialysis dose that has been named whole body Kt/V. The measured urea mass removal rate and the slope of the dialysate urea concentration curve are the key parameters needed for the calculations. No assumptions have to be made about urea distribution in the body (single or double pool, etc.). Blood sampling is not needed. This simplifies the logistics and eliminates the problems with rebound and timing in taking samples. The total urea mass present in the body before treatment is also obtained. It can be used directly, or in relation to body weight or water volume, as a measure of the level of urea in the body. This may serve as an alternative to pretreatment plasma concentration. If a pretreatment plasma urea concentration is available, the urea distribution volume can be calculated, which may be of separate clinical interest.

Whole body urea kinetics.

Improved methods are needed for dose quantification in dialysis because the kinetic modelling based on blood side urea concentrations, as currently used, is subject to several theoretical and practical problems. Since the treatment induces a disequilibrium, it is necessary to make assumptions about the distribution and exchange of urea within the body. A new method is presented which avoids these problems. The amount of urea removed is determined from continuous measurements in the spent dialysate. It is shown that the relative dialysis efficiency K/V can be calculated from the mass removal rate in relation to the mass remaining in the body, which is also determined from the measurements. As a by-product the total mass of urea in the body before the treatment is obtained. This can be used together with the blood concentration to calculate the urea distribution volume, which might be used as an additional clinical parameter. The new method was tested in three in vitro treatments of a container with a known amount of urea added to a known volume of dialysate. The calculated dose KT/V and initial urea mass differed from the true values by less than 3%.

Conductivity: On-Line Monitoring of Dialysis Adequacy

Cardiovascular disease and the inadequacy of delivered dialysis are the main factors determining morbidity and mortality in dialysis patients. We have already demonstrated that a conductivity kinetic model makes it possible to match interdialytic sodium loading and intradialytic sodium removal (the main factor determining cardiovascular morbidity) without the need for blood samples and, thus, in routine clinical practice. The aim of the present study was to test the possibility of using the conductivity method also to determine Kt/v without blood or dialysate sampling. In 18 steady-state patients, the urea distribution volume (V) was kinetically determined once using ionic dialysance (D) values instead of those of effective urea clearance. One month later, the Kt/V was determined by using the current D and T values and the predetermined V (Dt/V), then compared with the equilibrated Kt/V computed by means of the SPVV kinetic model (eqKt/V). The mean value of Dt/V was 1.18+/-0.15; while of eqKt/V it was 1.18+/-0.16, with a mean difference of 0.00+/-0.07. The conductivity method therefore seems to be very promising not only for monitoring the sodium balance, but also for quantifying delivered dialysis. Since its simplicity and low-cost make it suitable for use at each dialysis session, the conductivity method could therefore lead to significant progress in dialytic practice by contributing to the elimination of the two main causes of morbidity and mortality in dialysis patients.

Predialysis urea concentration is sufficient to characterize hemodialysis adequacy.

Mathematical description of urea kinetics for a week showed that, under steady state conditions (i.e., total removal equals total synthesis), any predialysis urea concentration is expressed as a linear function of specific urea generation (G/V) and of dialysis schedule timing and sessional Kt/V (product of clearance, K, and session time, t, divided by the urea distribution volume, V). It also predicts that TACurea is proportional to the predialysis concentrations. The ratio between the two depends linearly on delivered weekly dialysis dose ([wDD] = T(G/V)/TACurea, with T the number of hours in 1 week). These hypotheses have been tested by retrospectively analyzing urea kinetc modelling data that include all predialysis and post dialysis concentrations of 163 patient-weeks. All patients were anuric, and dialysis frequency was thrice weekly. Accuracy is assessed with regression analysis between database numbers and computed values. The theoretical ratio between midweek concentration and TACurea (1.43) is close to the computed ratio (1.46, r2 = 0.909). TACurea (slope = 1.002, r2 = 0.997), specific generation rate G/V as a precursor to PCRn (slope = 1.007, r2 = 0.985), and wDD (slope = 1.002, r2 = 0.909) are all accurately computed from predialysis concentrations. To aid in the determination of the ratio for the different predialysis, concentrations using wDD a nomogram is included.

Assessment of efficiency using on-line urea kinetic modeling in hemodiafiltration.

Urea kinetics has recently been re-evaluated using an on-line urea monitoring system applied to hemodiafiltration. This system allows evaluation of different components possibly responsible for the gap between prescribed and delivered dose of dialysis, such as access and cardiopulmonary recirculation, and altered dialysis parameters, such as blood flow and dialysate flow rates. Furthermore, the system allows prediction of postdialysis rebound urea concentrations. The aim of the present study was to apply the on-line urea monitoring system to assess the dialytic efficiency of double chamber hemodiafiltration in different conditions of blood-dialysate flow rates, reinfusion volumes, and dialyzer configurations (high + low flux membranes or high + high flux membranes) in 10 patients (age, 60 +/- 9 years; dry weight, 65 +/- 5 kg). There was a significantly lower Kt/V (K, dialyzer clearance; t, dialysis time; V, urea distribution volume) at equilibrium with the high + high vs high + low flux configuration, possibly because of a higher tendency toward urea compartmentalization. This difference was evident when reinfusion was performed post dilution. These studies support the concept that small molecular weight uremic toxins may be more efficiently removed using low flux membranes in a modified form of hemodiafiltration.

Plasma Iohexol Clearance in Automated Peritoneal Dialysis -its Role in Adequacy Determination

To compare the relationship of plasma iohexol clearance to standard adequacy measures in an automated peritoneal dialysis (APD) population. Prospective, nonrandomized, open label, simultaneous clearance studies of novel (iohexol) and traditional (urea and creatinine) markers of dialysis quantitation. Outpatient peritoneal dialysis units associated with tertiary care university hospitals. Eighteen stable patients, 13 undergoing continuous cycling peritoneal dialysis (CCPD) and 5 receiving intermittent dialysis, who underwent 24-hour clearance studies were enrolled in and completed the study. Each subject received 15 mL of iohexol intravenously the morning of a scheduled dialysis night. Blood was obtained for determination of serum concentrations of urea nitrogen and creatinine, and plasma iohexol concentration. Dialysate and urine were collected over 24 hours. Urea and creatinine data from the total pooled dialysate and from the 24-hour urine collection were used to calculate daily Kt/Vurea and normalized total daily creatinine clearance (CrCl). Total plasma iohexol clearance was calculated using a one-compartment model with the Brochner-Mortensen correction. Normalized [to 1.73 m2 body surface area (BSA)] iohexol clearance correlated very well with normalized CrCl (r2 = 0.777; p < 0.001). A weaker correlation was observed between Kt/Vurea and normalized iohexol clearance (r2 = 0.213; 0.05 < p < 0.1). When data are not normalized using BSA or urea distribution volume, the regressions are improved for both creatinine (r2 = 0.820) and urea (r2 = 0.533). These results were comparable between those on CCPD and those on intermittent therapy. Total plasma iohexol clearance provides a simple assessment for APD adequacy by eliminating collection problems inherent to the methodologies currently employed. Such simplicity allows for more frequent assessments of delivered dialysis dose and efficacy of prescription changes.

Is Post-Dialysis Urea Rebound Significant with Long Slow Hemodialysis?

Background: According to previous studies, postdialysis urea rebound (PDUR) is achieved within 30–90 min, leading to an overestimation of Kt/V of between 15 and 40% in 3- to 5-hour dialysis. The purpose of the study was to assess the impact of PDUR on the urea reduction ratio (URR), Kt/V and normal protein catabolic rate (nPCR) with long 8-hour slow hemodialysis. Methods: This study was performed in 18 patients (13 males/5 females), 62.5 ± 11.7 years of age, hemodialyzed for 3–265 months. Initial nephropathies were: 3 diabetes; 2 polycystic kidney disease; 3 interstitial nephritis; 2 nephrosclerosis; 3 chronic glomerulonephritis, and 5 undetermined. Residual renal function was negligible. The dialysis sessions were performed using 1- to 1.8-m² cellulosic dialyzers during 8 h, 3 times a week. Blood flow was 220 ml/min, dialysate flow 500 ml/min, acetate or bicarbonate buffer was used. Serial measurements of the urea concentration were obtained before dialysis, immediately after dialysis (low flow at t = 0), and at 5, 10, 20, 30, 40, 60, 90 and 120 min, and before the next session. The low-flow method was used to evaluate the access recirculation, second-generation Daugirdas formulas for Kt/V, and Watson formulas for total body water volume estimation. The difference between the expected urea generation (UG) and urea measured after dialysis (global PDUR) defines net PDUR (n-PDUR). Results: The n-PDUR usually became stable after 58 ± 25 (30–90) min. Its mean value was 17 ± 10% of the 30-second low-flow postdialysis urea (3.9 ± 2 mmol/l). This small postdialysis urea value and the importance of UG in comparison with shorter dialysis justify the use of n-PDUR. Ignoring n-PDUR would lead to a significant 4% overestimation (p < 0.001) of the URR (79 ± 7 vs. 76 ± 8%), 12% of Kt/V (1.9 ± 0.4 to 1.7 ± 0.38) and 4% of the nPCR (1.1 ± 0.3 to 1.05 ± 0.3). n-PDUR correlated negatively with postdialysis urea (r = 0.45 p = 0.05), positively with URR (r = 0.31 p = 0.01) and Kt/V (r = 0.3 p = 0.03) but not with K, and negatively with the urea distribution volume (r = 0.33 p = 0.05). Mean total recirculation, ultrafiltration rate, predialysis urea levels and urea clearance did not correlate with n-PDUR. Conclusion: We found a significant PDUR in long-slow hemodialysis after a mean of 1 h after dialysis. This PDUR has a less important impact upon dialysis delivery estimation than short 3- to 5-hour hemodialysis, especially for the lower Kt/V or URR ranges. This is explained by the low-flux, high-efficiency, and long-term dialysis. Its inter-individual variability incites us to calculate PDUR on an individual basis.

On-line assessment of delivered dialysis dose: Technical Note

The adequacy of the delivered dialysis dose is essential to prevent patient morbidity and mortality. The determination of effective ionic dialysance (D) is easy, non-invasive and inexpensive, and its use instead of effective urea clearance (K) in kinetically determining apparent" urea distribution volume (Vt) is likely to lead to a correct Kt/V, even though the Vt value may be incorrect. The aim of this study was to test the possibility of using the measurement of D to monitor Kt/V on-line during each dialysis treatment. Forty-four patients were dialyzed using a monitor equipped with specially designed "Diascan Module" (COT; Hospal) that measures effective D by means of a single conductivity probe. Vt was calculated according to the SPVV three BUN method urea kinetic model using D instead of K values. One month later, Kt/V was calculated as Dt/V, using actual D and T values and the predetermined Vt values updated for the current final body wt. Both the Dt/V and Kt/V determined according to the Smye and Daugirdas methods were compared with the Kt/V determined using the SPVV kinetic model (Kt/Veq) The Kt/V values calculated using ionic dialysance and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/- 0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17, mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). Once Vt has been determined, the evaluation of ionic dialysance in stable patients makes it possible to calculate the Kt/V accurately at each dialysis session without blood or dialysate sampling, and at no additional cost.

Urea kinetic modeling for CRRT

Urea kinetic modeling (UKM) for dialysis quantification and prescription, although widely used in chronic renal failure (CRF), has been largely absent in the acute setting. A quantitative approach to prescription of continuous renal replacement therapies (CRRTs) for acute renal failure (ARF) based on UKM is presented. For patients with a relatively constant urea generation rate, G, who are receiving a fixed dose of CRRT, blood urea nitrogen (BUN) falls in an exponential fashion, approaching a plateau level after 3 to 4 days of continuous treatment. The CRRT clearance, K, necessary to achieve a desired plateau value of BUN, C goal, may be computed as G/C goal × K for all but predilutional CRRT modalities may be calculated as equal to the effluent (dialysate plus ultrafiltrate) flow rate from the filter. Urea mass balance equations are proposed for the determination of patient G value either during the pretreatment rise in BUN or during the decline in BUN with CRRT. In the absence of a reliable estimate of patient G, a reasonable CRRT starting prescription is to set the filter effluent rate in liters per hour (≈K) to 1.2 times the patient's body weight in kilograms divided by the desired C goal in milligrams per deciliter. This relationship assumes moderate hypercatabolism (normalized protein catabolic rate = 2.0 g/kg/d) and patient urea distribution volume equal to 60% of body weight. For C goal = 60 mg/dL, this reduces to an easily remembered formula for K (in L/hr) of twice the patient's body weight divided by 100.

Effect of a two compartment distribution on apparent urea distribution volume

Blood-based urea kinetic modeling (UKM) permits estimation of the urea distribution volume V that may be compared with the anthropometrically-predicted volume to determine if the kinetic modeling results are plausible. Various confounding factors may cause differences between the true distribution volume and that measured by UKM. During hemodialysis, three principal mechanisms are likely to contribute to an effective multicompartmental distribution of urea: access recirculation, cardiopulmonary recirculation and distribution of urea between intraand extracellular, and/or low and high blood flow, compartments [1]. The effect of each of these mechanisms is to reduce the efficiency of dialysis by lowering the intradialytic serum blood urea nitrogen (BUN) profile. After dialysis, the serum BUN level will rebound with different time scales for access recirculation (over a period of approximately 10 seconds [1]), cardiopulmonary recirculation (typically over a period of 2 mm [2]), and the compartmental effects (over a period of 30 to 60 mm [3, 4]). Ideally blood drawn for urea kinetic modeling should be drawn after all three rebounds have occurred, 30 to 60 minutes postdialysis. If this is done, single-pool modelling based on the expected dialyzer urea clearance estimate will give an inflated estimate of the urea distribution volume. Single pool modeling assumes that the dialyzer clearance results in a monoexponentially decreasing plasma urea profile from the preto the post-dialysis BUN samples. Because of the recirculation/compartmental effects noted above effective dialyzer clearance will be less than that expected (K), and this is mathematically equivalent to an increased urea distribution volume V for a given exponent K/V. When blood is sampled before rebound has occurred, the situation is more complex; single-pool IJKIvI can underestimate, correctly estimate, or overestimate the true urea distribution volume, depending on the level of urea reduction that has occurred [1, 5]. This is because two counteracting effects are in play [6]. On the one hand, the fraction of urea distribution volume cleared (Kt/V) is overestimated, and this causes an underestimation of the urea distribution volume for the expected V value. On the other hand, the intradialytic urea profile is still lower than that estimated by a monoexponential curve from the predialysis BUN

Ionic dialysance as a method for the on-line monitoring of delivered dialysis without blood sampling

It is well known that the difference between prescribed and delivered dialysis doses greatly affects the morbidity and mortality of dialysed patients. The on-line monitoring of delivered dialysis is therefore of paramount importance. Recently, a conductivity- based method for determining Kt/V on a routine basis has been proposed. The study was performed using a specially designed module (Biofeedback Module, COT, Hospal) which, when connected to a dialysis monitor, automatically determines effective ionic dialysance (ID). During three consecutive dialysis sessions, administered to each of eight patients at the same depurative efficiency, we determined Kt/V by using mean effective ionic dialysance and by assuming, as suggested, that urea distribution volume corresponded to 55% of body weight. This method was compared with the gold standard of the direct quantification method. The Kt/V was also calculated by using mean effective ionic dialysance and the volume of urea distribution derived from anthropometric parameters. The Kt/V determined by using mean effective ionic dialysance and by assuming that urea distribution volume corresponded to 55% of body weight was heavily underestimated (−22%). This difference was due to both the overestimate of urea distribution volume (+l7%) and underestimate of effective urea clearance (Kueff) (−11%). The mean Kt/V calculated on the basis of ionic dialysance and anthropometric volume was also underestimated (−23%) since this volume was overestimated (+17%). Nevertheless, ionic dialysance and urea clearance proved to be closely correlated (r2=0.89) so that effective urea clearance can be derived according to: Kueff=ID×0.865+39.89. In steady-state patients, once urea distribution volume has been correctly determined by means of direct quantification, effective urea clearance can be easily derived from ionic dialysance and Kt/V calculated on-line at each session, without blood sampling or any additional costs.

Effect of access recirculation on the modeled urea distribution volume

The effect of vascular access recirculation (AR) on the modeled urea distribution volume (V) is not straightforward. When blood is sampled properly so that it is not admixed with recirculated blood, AR will cause an unexplained increase in V in cases in which AR is present throughout the dialysis session (when AR is limited to the terminal portion of a dialysis session it will cause little or no change in the modeled V). On the other hand, when blood is sampled from the arterial line after simply stopping the pump, postdialysis blood urea nitrogen (BUN) represents arterial line BUN and does not always reflect the BUN in the patient's blood. Under these conditions, when AR is present throughout the dialysis session the modeled V usually shows an unexplained decrease, but V may be unchanged, depending on the urea reduction ratio (URR). We performed a mathematical analysis to predict when V would be decreased and when it would be unchanged when the postdialysis BUN is contaminated with admixed blood. The analysis revealed that when AR is present uniformly throughout the dialysis session, the modeled V should be underestimated when the URR is ≤0.70. When the URR is greater than 0.70, even severe degrees of AR may not be reflected by a change in V. When AR is limited to the terminal part of the dialysis session or when AR increases during the dialysis session, and when V is based on admixed postdialysis blood, underestimation of V will occur in almost all circumstances. In a cross-sectional comparison of modeled to anthropometric volume ratios in eight patients with severe AR and in 11 controls, and in sequential modeling studies in a single patient in whom severe AR developed gradually over time, the volume ratio was low in most, but not all instances when modeled V was based on an admixed postdialysis BUN sample.

A mathematical analysis of a two-compartment model of urea kinetics

A model of urea distribution comprising well-mixed intracellular and extracellular compartments, with diffusive transfer of urea between compartments, is used to study blood urea variation during haemodialysis. Assuming that a typical adult patient (weight 70 kg and urea generation rate 5 mg min-1) is dialysed using a high-efficiency dialyser (urea clearance 0.2-0.251 min-1) at an ultrafiltration rate of 10 ml min-1, it is shown that a perturbation analysis can account for the effects of ultrafiltration and urea generation. This permits an analytical solution of the equations which describe the variation in solute concentration in each of the compartments, which may be compared with the solution obtained when urea generation and ultrafiltration are neglected. For a typical adult patient with urea distribution volume in the range 25-40 l undergoing high-efficiency haemodialysis, the analysis suggests that the contribution of ultrafiltration to the variation in urea concentration during dialysis is similar in magnitude to the experimental errors in measuring the blood concentration of urea and that a constant volume model will be sufficiently accurate to describe urea clearance in many patients.

Bioelectrical Impedance and Hemodialysis

Bioimpedance is a simple and non-invasive method of assessing body fluid composition. The aim of our study was to evaluate the reilability of impedance: a) to measure urea distribution volume considered to be coextensive with total body water (TBW); b) to assess the changes in body fluid compartments before and after dialysis; c) to predict hypotensive episodes. In twelve hemodialysis patients, TBW measured by bioelectrical impedance analysis (BIA) before a dialysis session was significantly correlated with the urea distribution volume estimated by dialysis direct quantification (r = 0.64, p < 0.05) and with TBW calculated by the Watson equation (r = 0.65, p < 0.05). Anthropometric values were, on average, 4.8% higher. TBW measured by BIA at the end of treatment overestimated fluid losses induced by ultrafiltration by 14% to 70%, while TBW 6 h after dialysis reflected the weight losses. On line BIA during hemodialysis has a very low positive predictive value (41.6%) and poor sensitivity (66%) for the prediction of hypotension. In conclusion, BIA is helpful in assessing the urea distribution volume but is not reliable for assessing acute fluid changes nor for predicting hypotensive episodes related to hemodialysis.