Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS.

Hemodiafiltration (HDF) is used sporadically for renal replacement therapy in Europe but not in the US. Characteristics and outcomes were compared for patients receiving HDF versus hemodialysis (HD) in five European countries in the Dialysis Outcomes and Practice Patterns Study. The study followed 2165 patients from 1998 to 2001, stratified into four groups: low- and high-flux HD, and low- and high-efficiency HDF. Patient characteristics including age, sex, 14 comorbid conditions, and time on dialysis were compared between each group using multivariate logistic regression. Cox proportional hazards regression assessed adjusted differences in mortality risk. Prevalence of HDF ranged from 1.8% in Spain to 20.1% in Italy. Compared to low-flux HD, patients receiving low-efficiency HDF had significantly longer average duration of end-stage renal disease (7.0 versus 4.7 years), more history of cancer (15.4 versus 8.7%), and lower phosphorus (5.3 versus 5.6 mg/dl); patients receiving high-efficiency HDF had significantly more lung disease (15.5 versus 10.2%) and received a higher single-pool Kt/V (1.44 versus 1.35). High-efficiency HDF patients had lower crude mortality rates than low-flux HD patients. After adjustment, high-efficiency HDF patients had a significant 35% lower mortality risk than those receiving low-flux HD (relative risk=0.65, P=0.01). These observational results suggest that HDF may improve patient survival independently of its higher dialysis dose. Owing to possible selection bias, the potential benefits of HDF must be tested by controlled clinical trials before recommendations can be made for clinical practice.

Extended daily dialysis vs. continuous hemodialysis for ICU patients with acute renal failure: a two-year single center report.

Extended daily dialysis (EDD) is an easily implemented alternative to continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). Since EDD offers most of the advantages of CRRT, we sought to compare the effectiveness of these two modalities. In this 2-year study, 54 ICU patients with ARF were treated with either continuous hemodialysis (CHD) or EDD. Oliguria was present in 64% of patients who received CHD vs. 73% of EDD patients (p=NS) while 93% of CHD and 81% of EDD patients required mechanical ventilation (p=NS). Patients treated with EDD were younger than those who received CHD (47.0 +/- 12.6 vs. 56.7 +/- 13.7, p=0.009), but there were no significant differences in gender or mean APACHE II scores at the time of randomization. Mean arterial blood pressures measured during treatment were maintained between 70 and 80 mmHg for both EDD and CHD and average daily serum electrolyte levels fell within normal ranges for EDD and CHD. Average daily fluid input and output were 5.8 +/- 3.3 L and 6.0 +/- 3.2 L for CHD vs. 3.3 +/- 2.6 and 3.0 +/- 1.7 L for EDD after exclusion of data from 2 burn patients. Hourly heparin anticoagulation rates were 1080 U/hour for CHD and 643 U/hour for EDD, p=0.02. Anticoagulation-free treatments were performed during 43% of all EDD treatments vs. 21% of all CHD treatments, p<0.001. Clotting of the dialyzer or circuit occurred at least once during 51% of all CHD treatment days vs. 22% of EDD treatments (p<0.001). We conclude that EDD is a safe, effective alternative to CRRT that offers comparable hemodynamic stability and excellent small solute control.

Daily hemodialysis efficiency: an analysis of solute kinetics.

Increasing the frequency of hemodialysis increases its efficiency, which causes the popular dialysis yardstick, single-pool Kt/V, to underestimate the dose just as it overestimates the dose of less frequent dialysis. The frequency dependence of hemodialysis can be explained by examining solute kinetics. Several factors, including the logarithmic fall in solute concentration and solute disequilibrium within the patient, account for the improved efficiency of both daily hemodialysis and continuous peritoneal dialysis, but to fully explain the marked difference in clinical targets for dosing peritoneal versus hemodialysis, one must go outside the realm of urea kinetics. Solutes that dialyze easily, such as urea, but diffuse less readily within the patient, require a 2-compartment model to accurately predict their concentration profiles and to measure efficiency. When applied to appropriately selected solutes, the model can account for the difference in clinical targets and can explain the failure of other indices, such as middle molecule clearance, eKt/V, and EKR, to account for the differences. A cumulative toxic effect of these relatively secluded compounds might offer a better explanation of uremic toxicity and an objective rationale for increasing dialysis frequency and time. Simplified methods for measuring the dose of dialysis fail when the patient is treated more often than 3 times per week, but 2 new and independently derived methods that include parameters to account for the improved efficiency have been developed for measuring frequent dialysis. The new expressions of dose as a weekly analog of urea clearance are similar in magnitude and independent of frequency, giving present-day clinicians a choice of methods to compare 2 to 7 treatments per week. The kinetic behavior of solutes removed by dialysis and the new expressions of dose support the subjective improvement reported by patients, many of whom have embraced a transition to more frequent and prolonged hemodialysis.

Uremic toxicity: urea and beyond.

Successful replacement of renal function with dialysis supports the concept that uremia is a toxic state resulting from accumulated solutes and that toxicity results from high concentrations of these solutes in body fluids. Dialyzer clearance of urea, a surrogate toxin, is the currently accepted best measure of dialysis and dialysis adequacy, but it is admittedly a compromise due to current lack of knowledge about and inability to measure more toxic solutes. This failure could be explained if uremic toxicity is actually a summation effect of multiple toxins, each at individual subtoxic levels in the patient. Other solutes could be used as surrogates to measure clearance, but urea happens to be available in high concentrations, is easily measured by all clinical laboratories, and is easily dialyzed, so changes in concentration are sensitive indicators of clearance. Measurements of creatinine clearance are confounded by the disequilibrium that occurs across red cells within the dialyzer and in the patient. Other solutes probably behave more like creatinine than urea, so urea stands out as uniquely diffusible, a property that actually spoils its effectiveness as a surrogate toxin, especially when applied to more frequent and continuous dialysis. Accumulation of other solutes may correlate better with toxic uremic symptoms and the residual syndrome. More studies are needed to examine the kinetics of other solutes, their generation rates, and their distribution volumes to provide clinicians with more knowledge and tools to optimize dialysis treatments. Examination of the effectiveness of solute removal in patients dialyzed more frequently may provide significant insight into the pathogenesis of uremia.

Catheter performance.

Venous catheters differ from peripheral arteriovenous (AV) access devices in many important ways. This discussion focuses on their performance as a conduit for blood flow between the patient and the dialyzer and on how catheter function is both limited and enhanced relative to the more common peripheral accesses. Catheter flow is limited by the high resistance inherent in the extended length of venous catheters relative to dialysis needles, but the high rate of flow in central veins also diminishes the opportunity for access recirculation. Cardiopulmonary recirculation is absent in patients with catheter access unless the patient also has a peripheral access. In the latter case, the same detrimental effect on urea clearance is seen regardless of which access device is used. Flow-dependent recirculation through circuits other than the peripheral AV access reduces the efficiency of dialysis (regardless of the type of access, catheter, or peripheral AV device used) across both catheters and peripheral AV devices. The inside diameter of the catheter plays a sensitive role in determining catheter resistance to flow. Slight increases in diameter under the same pressure head are associated with large increases in flow. Negative pressure at the catheter inflow port generated by the blood pump is magnified relative to peripheral devices, predisposing to partial collapse of the pump tubing segment and erroneous blood flow readings by the pump motor speed indicator. Setting a limit on prepump negative pressure can minimize this error. Future applications of dialysis may require lower pump speeds, which would allow more liberal use of catheter access if their potential for infection and clotting can be reduced.

Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit.

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

Relationship between apparent (single-pool) and true (double-pool) urea distribution volume.

BACKGROUND: The volume of urea distribution (V) is usually derived from single-pool variable volume urea kinetics. A theoretical analysis has shown that modeled single-pool V (Vsp) is overestimated when the urea reduction ratio (URR) is greater than 65 to 70% and is underestimated when the URR is less than 65%. The "true" volume derived from double-pool kinetics (Vdp) does not exhibit this effect. An equation has been derived to adjust Vsp to the expected Vdp. METHODS: To validate these theoretical predictions, we examined data from the Hemodialysis (HEMO) Study to assess the performance of Vdp as estimated from Vsp using the previously published prediction equation. For increased precision, both Vsp and Vdp were factored by anthropometric volume (Va). Patients were first dialyzed with a target equilibrated dialysis dose (eKt/V) of 1.45 during a baseline period and were then randomly assigned to eKt/V targets of either 1. 05 (a URR of approximately 67%) or 1.45 (a URR of approximately 75%). A blood sample was obtained one hour after starting dialysis during one dialysis in each patient. RESULTS: Vsp/Va was (mean +/- SD) 1.014 +/- 0.127 in 795 patients during the baseline period when the URR was approximately 1.45. During the first modeled dialysis after randomization, the Vsp/Va fell to 0.961 +/- 0.138 in the group with an eKt/V target of 1.05, but did not change significantly under the high eKt/V goal. The correction of Vsp to Vdp using the prediction equation resulted in a Vdp/Va ratio of 0.96 to 0.98 in all three circumstances without significant differences. When a blood sample was drawn one hour after starting dialysis, the apparent Vsp/Va ratio at one hour was much lower at 0.708 +/- 0.139. However, the mean Vdp/Va ratio, computed using the correction equation, was 0.968 +/- 0.322, which was similar to the Vdp/Va ratio calculated from the postdialysis blood urea nitrogen. CONCLUSIONS: These data suggest that the previously derived formula for adjusted Vsp is valid experimentally. The Vsp/Vdp correction should be useful for prescribing hemodialysis with either a very low Kt/V (for example, daily and early incremental dialysis) or a very high Kt/V.

Association of acidosis and nutritional parameters in hemodialysis patients.

There is extensive literature supporting an important role for acidosis in inducing net protein breakdown, both in experimental animals and humans. However, the clinical importance of the moderate intermittent metabolic acidosis frequently observed in hemodialysis patients has not been determined. We performed a cross-sectional analysis of the baseline laboratory data in the first 1,000 patients recruited to the Hemodialysis Study, looking for correlations between predialysis serum total carbon dioxide levels and parameters related to dietary intake and nutritional status. We found the mean predialysis serum total carbon dioxide level was moderately low (21.6 +/- 3.4 mmol/L; mean +/- SD) despite the use of bicarbonate dialysate and an average single-pool Kt/V of 1.54. Predialysis serum total carbon dioxide level correlated negatively with normalized protein catabolic rate (P < 0.001), suggesting patients with lower serum total carbon dioxide levels have a greater protein intake. The degree of acidosis observed in our patients does not seem to have a deleterious effect on the nutritional status of these patients because correlation of serum total carbon dioxide level with nutritional parameters, such as serum creatinine and serum albumin levels, was either negative or not statistically significant. Further investigation of the effect of modifying serum bicarbonate concentration on nutritional markers is needed to test these hypotheses.

Cardiac output and central blood volume during hemodialysis: methodology.

Cardiovascular disease is the leading cause of mortality in patients whose lives depend on hemodialysis. We developed a method for measuring cardiac output (CO) and central blood volume (CBV) in hemodialyzed patients that may help to elucidate the mechanisms and consequences of cardiac disease in this population. This report describes the technique, focusing on the main sources of error and how they can be prevented. Three principal sources of error were identified: (1) access recirculation (existing or induced during injection); (2) the second pass of the indicator through the cardiopulmonary system, exacerbated by prolonging the duration of intravenous injection; and (3) the transit time of the indicator through the dialysis blood lines. After the algorithms were adjusted to prevent the above errors, the reproducibility of CO and CBV, expressed as the absolute percent deviation from the average of duplicates (3,488 values duplicated within 5 minutes), was 4.3 +/- 3.8% for CO and 4.1 +/- 3.8% for CBV. To determine the clinical value of routine CO and CBV measurements, morbid events (nausea, vomiting, and/or muscle cramps) were prospectively recorded in 73 randomly selected hemodialysis patients. CO and CBV were measured near the beginning and near the end of 98 dialysis sessions during which 28 morbid events were identified. In 10 of these sessions, where morbid events took place within 30 minutes of the measurements, CBV appeared to be a more sensitive indicator of morbid events than CO. We conclude that CO and CBV can be routinely and reliably measured during hemodialysis if precautions are taken to avoid specifically identified sources of error. Preliminary studies suggest that these measurements may have significant prognostic value.

Imprecision of the hemodialysis dose when measured directly from urea removal. Hemodialysis Study Group.

BACKGROUND: The 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). METHODS: During 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 30 minutes 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. RESULTS: During 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. CONCLUSIONS: The 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.

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group.

Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta2-microglobulin (beta2M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse.

Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients.

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.

Lessons from the Hemodialysis (HEMO) Study: an improved measure of the actual hemodialysis dose.

The Hemodialysis (HEMO) Study is a multicenter, prospective, randomized, 2 x 2 factorial clinical trial designed to evaluate the efficacy of the dose of dialysis delivered ("standard" v "high") and dialysis membrane flux ("low" v "high") in reducing the morbidity and mortality of patients. The study is nearly half complete. Although both patients and investigators are blinded to the overall findings, which will not be available for another 3 years, important data have been generated from which a more accurate expression has been derived for the dose of dialysis received by each patient in the trial. This new expression of the effectiveness of dialysis, eKt/V, is a two-pool approximation derived from the traditional single-pool Kt/V (spKt/V) and time on dialysis. The dialysis prescription for the HEMO Study subjects is individualized to achieve the target dose for each patient and is closely monitored by measuring the more accurate and validated expression of eKt/N. Comparisons of the HEMO Study dose of dialysis with other studies have been confused by this unique expression (eKt/V) of the dialysis dose and adequacy adopted for the HEMO Study. The target eKt/V dose in the "standard" arm of the Study is 1.05 and in the "high" arm is 1.45 per dialysis thrice weekly. Based on data available from 426 subjects randomized to each arm, the target of 1.05 in the "standard" dose of the HEMO Study is equivalent to an spKt/V of 1.32, and that of the "high" dose, 1.67. Thus, volunteers in the "standard" arm of the Study are receiving a tightly controlled and closely monitored dose, which is above the current national mean spKt/V, and above that of the accepted minimum standard spKt/N of 1.2. When completed, the HEMO Study will show whether there are merits of a tightly controlled hemodialysis dose that is consistently delivered over a prolonged period and whether a high dose is beneficial and safe to prescribe.

In vivo measurement of hemodialyzer fiber bundle volume: theory and validation.

BACKGROUND: Fiber bundle volume (FBV), the space within the blood compartment of hollow fiber dialyzers, may decrease during treatment due to clotting. The clots may be flushed out of the dialyzer prior to measurements of FBV by dialyzer reprocessing equipment and a significant drop in FBV during the session may go unrecognized. METHODS: FBV was measured (1) from the transit time of a saline bolus passing through the dialyzer as recorded by ultrasound dilution sensors placed on the arterial and venous blood lines; (2) from the change in blood concentration induced by a step change in the rate of ultrafiltration as recorded by the venous sensor. RESULTS: In vitro FBV ranged from 47 to 121 ml. Paired absolute differences between the ultrasound and volumetric measurements (flushing saline out of the dialyzer into a graduated cylinder) were 0.16 +/- 4.23% (N = 42) and 2.10 +/- 7.26% (N = 13) for the bolus and ultrafiltration methods, respectively. In vivo reproducibility of the bolus and ultrafiltration methods were 2.65 +/- 2.11% (N = 122) and 3.79 +/- 3.93% (N = 32), respectively. During 31 treatments the FBV by dilution showed an average decrease of 4.17 +/- 8.60%, and in 6 cases FBV fell more than 10%, while measurements of the same FBV by reuse equipment showed an increase of 0.99 +/- 5.82%, P < 0.01. CONCLUSIONS: FBV measured by the dilution methods was accurate and reproducible. Preliminary results suggest that in vivo FBV may differ significantly from results reported by reprocessing machines.

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.