Pathophysiology of dialysis hypotension: an update.

Dialysis hypotension occurs because a large volume of blood water and solutes are removed over a short period of time, overwhelming normal compensatory mechanisms, including plasma refilling and reduction of venous capacity, due to reduction of pressure transmission to veins. In some patients, seemingly paradoxical and inappropriate reduction of sympathetic tone may occur, causing reduction of arteriolar resistance, increased transmission of pressure to veins, and corresponding increase in venous capacity. Increased sequestration of blood in veins under conditions of hypovolemia reduces cardiac filling, cardiac output, and, ultimately, blood pressure. Adenosine release due to tissue ischemia may participate in reducing norepinephrine release locally, and activation of the Bezold-Jarisch reflex, perhaps in patients with certain but as yet undefined cardiac pathology, may be responsible for sudden dialysis hypotension. Patients with diastolic dysfunction may be more sensitive to the effects of reduced cardiac filling. The ultimate solution is reducing the ultrafiltration rate by use of longer dialysis sessions, more frequent dialysis, or reduction in salt intake. Increasing dialysis solution sodium chloride levels helps maintain blood volume and refilling but ultimately increases thirst and interdialytic weight gain, with a possible adverse effect on hypertension. Blood volume monitoring with ultrafiltration or dialysis solution sodium feedback loops are promising new strategies. Maintaining tissue oxygenation via an adequate blood hemoglobin level seems to be important. Use of adenosine antagonists remains experimental. Given the importance of sympathetic withdrawal, the use of pharmacologic sympathetic agonists is theoretically an attractive therapeutic strategy.

Compartment effects in hemodialysis.

Compartment effects in hemodialysis are important because they reduce the efficiency of removal of the compartmentalized solute during dialysis. The dialyzer can only remove those waste products that are presented to it, and then only in proportion to the concentration of the solute in the blood. Classically a two-compartment system has been modeled, with the compartments arranged in series. Because modeling suggests that the sequestered compartment is larger than the accessible compartment, an assumption has been made that the sequestered compartment is the intracellular space. For urea and other solutes that move easily across many cell membranes, compartmentalization may be flow related, that is, related to sequestration in organs (muscle, skin, bone). Although mathematically urea rebound and mass balance can be described with either model, the flow-related model best explains data showing that urea rebound after dialysis is increased during ultrafiltration, diminished during high cardiac output states, and also reduced during exercise. Whether compartmentalization is increased in vasoconstricted intensive care unit patients receiving acute dialysis remains an open question.

Mortality risk by hemodialyzer reuse practice and dialyzer membrane characteristics: results from the usrds dialysis morbidity and mortality study.

Hemodialyzer reuse is commonly practiced in the United States. Recent studies have raised concerns about the mortality risk associated with certain reuse practices. We evaluated adjusted mortality risk during 1- to 2-year follow-up in a representative sample of 12,791 chronic hemodialysis patients treated in 1,394 dialysis facilities from 1994 through 1995. Medical record abstraction provided data on reuse practice, use of bleach, dialyzer membrane, dialysis dose, and patient characteristics and comorbidity. Mortality risk was analyzed by bootstrapped Cox models by (1) no reuse versus reuse, (2) reuse agent, and (3) dialyzer membrane with and without the use of bleach, while considering dialysis and patient factors. The relative risk (RR) for mortality did not differ for patients in reuse versus no-reuse units (RR = 0.96; 95% confidence interval [CI], 0.86 to 1.08; P > 0.50), and similar results were found with different levels of adjustment and subgroups (RR = 1.01 to 1.05; 95% CI, lower bound > 0.90, upper bound < 1.19 each; each P > 0.40). The RR for peracetic acid mixture versus formalin varied significantly by membrane type and use of bleach during reprocessing, achieving borderline significance for synthetic membranes. Among synthetic membranes, mortality was greater with low-flux than high-flux membranes (RR = 1.24; 95% CI, 1.02 to 1.52; P = 0.04) and without than with bleach during reprocessing (RR = 1.24; 95% CI, 1.01 to 1.48; P = 0.04). Among all membranes, mortality was lowest for patients treated with high-flux synthetic membranes (RR = 0.82; 95% CI, 0.72 to 0.93; P = 0.002). Although mortality was not greater in reuse than no-reuse units overall, differences may exist in mortality risk by reuse agent. Use of high-flux synthetic membrane dialyzers was associated with lower mortality risk, particularly when exposed to bleach. Clearance of larger molecules may have a role.

Stability of urea and creatinine in spent hemodialysate.

Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours. In the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products.

Body size, dose of hemodialysis, and mortality.

This study investigates the role of body size on the mortality risk associated with dialysis dose in chronic hemodialysis patients. A national US random sample from the US Renal Data System was used for this observational longitudinal study of 2-year mortality. Prevalent hemodialysis patients treated between 1990 and 1995 were included (n = 9,165). A Cox proportional hazards model, adjusting for patient characteristics, was used to calculate the relative risk (RR) for mortality. Both dialysis dose (equilibrated Kt/V [eKt/V]) and body size (body weight, body volume, and body mass index) were independently and significantly (P < 0.01 for each measure) inversely related to mortality when adjusted for age and diabetes. Mortality was less among larger patients and those receiving greater eKt/V. The overall association of mortality risk with eKt/V was negative and significant in all patient subgroups defined by body size and by race-sex categories in the range 0.6 < eKt/V < 1.6. The association was negative in the restricted range 0.9 < eKt/V < 1.6 (although not generally significant) for all body-size subgroups and for three of four race-by-sex subgroups, excepting black men (RR = 1. 003/0.1 eKt/V; P > 0.95). These findings suggest that dose of dialysis and several measures of body size are important and independent correlates of mortality. These results suggest that patient management protocols should attempt to ensure both good patient nutrition and adequate dose of dialysis, in addition to managing coexisting medical conditions.

Prescription of twice-weekly hemodialysis in the USA.

BACKGROUND/AIMS: The purpose of this study was to investigate the frequency and characteristics of two hemodialysis sessions/week, to identify factors which influence or predict this prescription, and to examine the outcomes of patients receiving hemodialysis two times/week as compared to the more common treatment of three times/week. METHODS: Data from a national sample of 15,067 adult hemodialysis patients were utilized to compare twice-weekly with thrice-weekly therapy by logistic regression. RESULTS: Patients treated less than one year were more likely to be treated twice-weekly (6.1%) than patients on dialysis for one year or more (2.7%) (AOR = 1.49, p = 0.002). Treatment schedules also varied significantly by geographic region. Factors predictive of twice-weekly hemodialysis (p < 0.05) were older age, Caucasian race, female gender, higher serum albumin, lower serum creatinine levels, and lower body mass index. A higher estimated renal function at the start of ESRD was also predictive of a twice-weekly schedule among incident patients (AOR = 1.05, p = 0.05). In addition, Cox-adjusted survival analysis indicated a lower mortality risk (RR = 0.76, p = 0. 02) for twice-weekly hemodialysis compared to thrice-weekly among prevalent patients. For incident patients, however, the results were not significant when adjusted for GFR at ESRD onset (RR = 0.85, p = 0.31). CONCLUSION: Geographic differences in prescribed treatment remained unexplained by measured characteristics. The survival advantage associated with twice-weekly hemodialysis is likely to be related to patient selection and greater residual renal function.

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.

Survival advantage in Asian American end-stage renal disease patients.

UNLABELLED: Survival advantage in Asian American end-stage renal disease patients. BACKGROUND: An earlier study documented a lower mortality risk for end-stage renal disease (ESRD) patients in Japan compared with the United States. We compared the mortality of Caucasian (white) and Asian American dialysis patients in the United States to evaluate whether Asian ancestry was associated with lower mortality in the United States. METHODS: The study sample from the U.S. Renal Data System census of ESRD patients treated in the United States included 84,192 white or Asian patients starting dialysis during May 1995 to April 1997, of whom 18,435 died by April 30, 1997. Patient characteristics were described by race. Relative mortality risks (RRs) for Asian Americans relative to whites were analyzed by Cox proportional hazards regression models adjusting for characteristics and comorbidities. Population death rates were derived from vital statistics for the United States and Japan by age and sex. RESULTS: Adjusting for demographics, diabetes, comorbidities, and nutritional factors, the RR for Asian Americans was 0.75 (P = 0.0001). Race-specific background population death rates accounted for over half of the race-related mortality difference. For whites, mortality decreased as the body mass index (BMI) increased. For Asians, the relationship between BMI and survival was u-shaped. The ratio of Asian American/white dialysis death rates and the ratio of Asian American/white general population death rates both varied by age in a similar pattern. The population death rates of Asian American and Japanese were also similar. CONCLUSION: Among dialysis patients, Asian Americans had a markedly lower adjusted RR than whites. The effect of BMI on survival differed by race. Compared with the respective general population, dialysis patients had the same relative increase in death rates for both races. The difference in death rates between the United States and Japan does not appear to be primarily treatment related, but rather is related to background death rates.

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.

Variation in blood sample collection for determination of hemodialysis adequacy. Council on Renal Nutrition National Research Question Collaborative Study Group.

Inadequate dialysis has been associated with high morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis. The accurate estimation of dialysis adequacy, measured either as a calculated urea kinetics (Kt/V) or a simple urea reduction ratio (URR) is dependent on the proper collection of blood samples for predialysis and postdialysis blood urea nitrogen (BUN) determination. Because no established protocol exists for blood sampling, we surveyed the study cohort of dialysis centers participating in the National Kidney Foundation Council on Renal Nutrition National Research Question Collaborative Study to determine the comparability of BUN data that were collected to calculate URR to determine adequacy of dialysis. Surveys were completed by 100% of the 202 units participating: 195 in the United States (from 43 states) and seven from Canada, treating approximately 15,000 hemodialysis patients in total. The distribution of the sample by the type of facility mirrored that of 1996 United States Renal Data System (USRDS) Annual Report facilities data. Results showed a 5.0% error in predialysis blood draw and an 8.4% to 41.6% error in the postdialysis counterpart. There was a large variability in the observed postdialysis methods in general. Dilution of predialysis sample with either heparin or saline will falsely underestimate Kt/V and URR. The presence of access-derived, recirculated blood in the postdialysis sample will falsely overestimate Kt/V and URR. Excessive delay in drawing postdialysis sample will reduce Kt/V and URR because of urea rebound. Adoption by all dialysis providers of a uniform blood sample draw procedure will result in a consistency necessary to allow reliable and valid comparison of adequacy of dialysis parameters within and between ESRD patients, units, and clinical trials.

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.

Splanchnic erythrocyte content decreases during hemodialysis: a new compensatory mechanism for hypovolemia.

Splanchnic and splenic erythrocyte volumes decrease during postural changes and exercise to help maintain central blood volume and cardiac output. The contribution of this compensatory mechanism to hemodynamic stability during dialysis has not been studied, however. In 8 ESRD patients, age 51.0 +/- 4.5 years old, we measured changes in the splanchnic/splenic erythrocyte volume during dialysis by tagging the patients' erythrocytes with technetium and following abdominal radioactivity over time. Splanchnic radioactivity decreased to 90.2 +/- 3.8% (mean +/- SEM) of the baseline value after 2 hr of accelerated fluid removal (3.7 +/- 0.4 liters) during dialysis (DUF), while it remained relatively unchanged after two hours of dialysis without fluid removal (DD) [106.5 +/- 2.3%, P (DUF vs. DD) = 0.03]. Splenic radioactivity decreased to 89.2 +/- 5.0% of the initial value during DUF versus 103 +/- 3.8% during DD, but the decrease was noted only during the last 30 minutes of DUF and did not attain statistical significance. Autonomic nervous system integrity was measured by the spontaneous variation of the R-R interval during deep respiration (E/I ratio) and by the Valsalva ratio. The mean E/I and Valsalva ratios in the eight patients were 1.13 +/- 0.03 (+/-SEM) and 1.42 +/- 0.1 respectively, suggesting reasonably adequate autonomic nervous system functioning. The results suggest that contraction of the splanchnic, and possibly the splenic, vascular beds occurs during fluid removal associated with hemodialysis. The resultant addition of erythrocytes to the circulation may help maintain central blood volume and cardiac output.

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The Hemodialysis (HEMO) Study.

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

Screening for extreme postdialysis urea rebound using the Smye method: patients with access recirculation identified when a slow flow method is not used to draw the postdialysis blood.

To look for patients with extreme urea rebound, we drew intradialytic samples one third of the way into dialysis during routine modeling for 3 months. The samples taken postdialysis were obtained after stopping the blood pump, without any slow flow period. Using the Smye equations, the intradialytic urea level was used to predict urea rebound, expressed as Kt/V-equilibrated minus Kt/V-single pool (deltaKt/V). Results were averaged for the 3-month period in 369 patients. Mean estimated deltaKt/V was -0.20 +/- 0.13, which was similar to but slightly higher than the predicted value (-0.6 x K/V + 0.03) of -0.19 +/- 0.04. In 27 patients, extreme rebound (mean deltaKt/V < -0.40) was found. Sixteen of these patients consented to further study, but only after access revision in four patients. In these patients, additional slow flow samples after 15 seconds and 2 minutes of slow flow, respectively, were drawn one third of the way into dialysis and postdialysis, and a sample was drawn 30 minutes after dialysis. On restudy, postdialysis rebound was still high with full flow samples deltaKt/V = -0.40 +/- 25, but was much lower (-0.18 +/- 0.07) and similar to predicted rebound (-0.19 +/- 0.05; P = NS) when based on 15-second slow flow samples. Eight of the 16 had marked (>15%) access recirculation by urea sampling, and deltaKt/V based on full flow post samples correlated with access recirculation (r = -0.91). The results suggest that the Smye method is valuable for identifying patients with aberrantly large postdialysis rebound values. When the postdialysis samples are drawn without an antecedent slow flow period, most patients with extreme rebound values turn out to have marked access recirculation.

Cardiac output and urea kinetics in dialysis patients: evidence supporting the regional blood flow model.

The regional blood flow model predicts that urea sequestration occurs in organs rather than cells, and that post-dialysis urea rebound is a function of both cardiac index (CI) and regional blood flow distribution to muscle. We measured cardiac output (CO) in 100 randomly selected dialysis patients using bioelectric impedance three times during a single dialysis. Mean CO was 5.8 +/- 2.1 liter/min and CI averaged 3.1 +/- 1.1 liter/min/M2. CI was negatively correlated with age (r = -0.48, P < 0.01). CI was strongly affected by vasodilator ingestion (yes, N = 36, CI = 3.5 +/- 1.2; no, N = 64, CI = 2.88 +/- 0.92, P < 0.006). CI was not associated with systolic, diastolic, or mean blood pressures, nor with Hct, although very few severely anemic patients were in the cohort. Repeat intra-dialytic CO measurements two to three months later in 15 patients with low CI (2.59 +/- 0.59 liter/min/M2) and in 13 patients with high CI (5.00 +/- 0.9, P < 0.001) during a urea kinetic modeling session including 30 minutes post-dialysis rebound, sampling showed highly reproducible values for CO, with a mean absolute value % difference between CO values measured several months apart of 9.0 +/- 17%, r = 0.92. Urea rebound expressed as the difference (delta Kt/V30) between equilibrated and single-pool Kt/V was lower in the high CI group (-0.099 +/- 0.07) than in the low CI group (-0.16 +/- 0.06, P = 0.026), and delta KT/V30 as well as delta Kt/V30 divided by K/V correlated with CI (r = 0.48 and 0.48, respectively, P < 0.01). The RBF model was used to compute a group mean predicted delta Kt/V30 for the low CI and high CI groups based on measured group mean values for CI and K/V. The predicted delta Kt/V30 values for the high CI group (-0.097) and the low CI group (-0.183) agreed closely with measured values. RBF modeled values of CO (7.46 +/- 2.96 liter/min) were not significantly different from impedance-derived CO (6.93 +/- 2.70 liter/min), and the two CO measures correlated significantly (r = 0.63, P = 0.0003). The results provide support for the regional blood flow model of urea kinetics.

The dose of hemodialysis and patient mortality.

The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study of a U.S. national sample of 2,311 patients from 347 dialysis units estimates the relationship of delivered hemodialysis dose to mortality, with a statistical adjustment for an extensive list of comorbidity/risk factors. Additionally this study investigated the existence of a dose beyond which more dialysis does not appear to lower mortality. We estimated patient survival using proportional hazards regression techniques, adjusting for 21 patient comorbidity/risk factors with stratification for nine Census regions. The patient sample was 2,311 Medicare hemodialysis patients treated with bicarbonate dialysate as of 12/31/90 who had end-stage renal disease for at least one year. Patient follow-up ranged between 1.5 and 2.4 years. The measurement of delivered therapy was based on two alternative measures of intradialytic urea reduction, the urea reduction ratio (URR) and Kt/V (with adjustment for urea generation and ultrafiltration). Hemodialysis patient mortality showed a strong and robust inverse correlation with delivered hemodialysis dose whether measured by Kt/V or by URR. Mortality risk was lower by 7% (P = 0.001) with each 0.1 higher level of delivered Kt/V. (Expressed in terms of URR, mortality was lower by 11% with each 5 percentage point higher URR; P = 0.001). Above a URR of 70% or a Kt/V of 1.3 these data did not provide statistical evidence of further reductions in mortality. In conclusion, the delivered dose of hemodialysis therapy is an important predictor of patient mortality. In a population of dialysis patients with a very high mortality rate, it appears that increasing the level of delivered therapy offers a practical and efficient means of lowering the mortality rate. The level of hemodialysis dose measured by URR or Kt/V beyond which the mortality rate does not continue to decrease, though not well defined with this study, appears to be above current levels of typical treatment of hemodialysis patients in the U.S.