URR

I have been reading the last day or so and I found a number sources of information- I have concluded that optimum clearance is 65% to 74%, after 75% the trade-off appears to be malnutrition which actually increases the mortal risk signifigantly.here is some of what I found- lets see if you draw the same conclusions,and if not help me understand.

Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (1999) 56, 1872–1878; doi:10.1046/j.1523-1755.1999.00734.x

Exploring the reverse J-shaped curve between urea reduction ratio and mortality
Glenn M Chertow, William F Owen, J Michael Lazarus, Nancy L Lew and Edmund G Lowrie

Divisions of Nephrology, Moffitt-Long Hospitals and UCSF-Mt. Zion Medical Center, Department of Medicine, University of California, San Francisco, California; Institute for Renal Outcomes Research and Health Policy, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; and Fresenius Medical Care North America, Lexington, Massachusetts, USA

Correspondence: Glenn M. Chertow, M.D., Division of Nephrology, University of California, San Francisco, 672 Health Sciences East, San Francisco, California 94143-0532, USA. E-mail: chertowg@medicine.ucsf.edu

Received 2 March 1999; Revised 28 May 1999; Accepted 7 June 1999.

Top of pageAbstract
Exploring the reverse J-shaped curve between urea reduction ratio and mortality.

Background Although accepted worldwide as valid measures of dialysis adequacy, neither the Kt/V (urea clearance determined by kinetic modeling) nor the urea reduction ratio (URR) have unambiguously predicted survival in hemodialysis patients. Because the ratio Kt/V can be high with either high Kt (clearance time) or low V (urea volume of distribution) and V may be a proxy for skeletal muscle mass and nutritional health, we hypothesized that the increase in the relative risk of death observed among individuals dialyzed in the top 10 to 20% of URR or Kt/V values might reflect a competing risk of malnutrition.

Methods A total of 3,009 patients who underwent bioelectrical impedance analysis were stratified into quintiles of URR. Laboratory indicators of nutritional status and two bioimpedance-derived parameters, phase angle and estimated total body water, were compared across quintiles. The relationship between dialysis dose and mortality was explored, with a focus on how V influenced the structure of the dose–mortality relationship.

Results There were statistically significant differences in all nutritional parameters across quintiles of URR or Kt/V, indicating that patients in the fifth quintile (mean URR, 74.4 3.1%) were more severely malnourished on average than patients in all or some of the other quintiles. The relationship between URR and mortality was decidedly curvilinear, resembling a reverse J shape that was confirmed by statistical analysis. An adjustment for the influence of V on URR or Kt/V was performed by evaluating the Kt-mortality relationship. There was no evidence of an increase in the relative risk of death among patients treated with high Kt. Higher Kt was associated with a better nutritional status.

Conclusion We conclude that the increase in mortality observed among those patients whose URR or Kt/V are among the top 10 to 20% of patients reflects a deleterious effect of malnutrition (manifest by a reduced V) that overcomes whatever benefit might be derived from an associated increase in urea clearance. Identification of patients who achieve extremely high URR (>75%) or single-pooled Kt/V (>1.6) values using standard dialysis prescriptions should prompt a careful assessment of nutritional status. Confounding by protein-calorie malnutrition may limit the utility of URR or Kt/V as a population-based measure of dialysis dose.

Keywords: dialysis adequacy, hemodialysis, mortality and dialysis, urea volume

Defining the dose of dialysis to optimize health and functional status for patients with end-stage renal disease (ESRD) has been among the principle goals of the nephrology community for more than two decades. In a landmark publication in 1985, Gotch and Sargent revolutionized the field of dialysis therapy with their reanalysis of data from the National Cooperative Dialysis Study (NCDS)1,2, redefining the dose of dialysis in terms of the clearance (K) time (t) product normalized to the urea volume of distribution (V), a dimensionless quantity derived from the fractional reduction in urea nitrogen (URR) achieved over the course of a hemodialysis treatment. These authors and others who followed them were successful at identifying a minimum dose of dialysis above which death and complications were less likely, although the optimal dose of dialysis remained unknown. Application of this methodology to other patient cohorts similarly showed that an increase in URR or Kt/V was generally associated with reduced mortality and less frequent complications3,4,5,6,7,8. Although it followed that further increases in dialysis dose might be expected to lead to fewer complications and better outcomes, Owen et al initially showed that there appeared to be a plateau at or around a URR of 60 to 65% [corresponding to a single-pooled Kt/V (spKt/V) of approximately 1.2, with considerable variation depending on the degree of ultrafiltration]8 beyond which no further improvement in survival could be demonstrated3. More recently, McClellan, Soucie, and Flanders showed that a URR of 70 to 74% was associated with an increased risk of death compared with a URR of 65 to 69%9. Following adjustment for a variety of covariates, the difference between the 70 to 74% and the 65 to 69% groups was not statistically significant, although the effect estimate was essentially unchanged (OR, 1.49 vs. 1.40). There was a trend toward an increased risk of death in the URR of 75 to 79% group. URR was also modeled as a continuous linear variable, although higher order URR terms (for example, URR squared) were not examined.

Toward explaining the paradox of increased mortality associated with greater URR, we hypothesized that there was a curvilinear relationship between dialysis dose and mortality and that the observed increase in mortality at high URR was a consequence of reduced body size (that is, malnutrition) among some of the high URR cohort. Because the majority of total body water is contained within skeletal muscle, a high Kt/V or URR typically requires a large clearance time product (Kt), as urea distribution volume is relatively fixed. However, within the relatively fixed Kt values delivered in the United States10, a large URR can also be achieved in patients who have little muscle mass, a manifestation of protein-calorie malnutrition. We had previously shown that in hemodialysis patients, total body water by deuterium oxide dilution was below population norms, both in absolute terms and as a fraction of body weight11. This large cohort of patients who underwent bioelectrical impedance analysis (BIA) afforded us the opportunity to explore the relationships among several indicators of nutritional status and URR. Furthermore, we were able to evaluate the structure of the URR–mortality relationship, with and without adjustment for total body water and other laboratory nutritional measures.

Top of pageMethods
Study subjects
Study subjects were 3009 prevalent adult hemodialysis patients from 101 free-standing Fresenius Medical Care North America (FMCNA) dialysis units across the United States. Inclusion criteria included age of 18 years and three times per week in-center hemodialysis for 3 months. Patients with an amputation above the transmetatarsal site were excluded from participation. BIA (BIA Quantum; RJL Systems, Inc., Clinton Township, MI, USA) was performed before a midweek dialysis session during the first six months of 1995. Briefly, an inner electrode was attached to the dorsal surface of the wrist on the arm without an arteriovenous fistula or graft. An outer electrode was placed on the dorsal surface of the third metacarpal bone. A second pair of electrodes was positioned on the anterior surface of the ipsilateral ankle and the dorsal surface of the third metatarsal bone12. A single frequency low-amplitude imperceptible current (800 mA at 50 kHz) was introduced via the electrodes on the hand and foot. The electrodes at the wrist and ankle detected the voltage decrease. The resistance and reactance in ohms were obtained directly from the device. Phase angle (the arc tangent of the reactance to resistance ratio) was calculated in radians and was multiplied by 180/ (approximately 3.14159265) to covert radians to degrees. Reactance, resistance, phase angle, and the derived estimates of total body water were merged with the Patient Statistical Profile, a database with selected demographic, historic, and laboratory information on patients cared for at FMCNA-affiliated dialysis facilities13. Laboratory values were means of the three months proceeding BIA testing. Kt/V was calculated using the equation ln (1 - URR/100) to avoid bias introduced by regression adjustment. Ultrafiltration volumes were not available. The clearance time product (Kt) was calculated by multiplying Kt/V by total body water derived from BIA. Alternative total body water estimates derived from the Watson, Watson, and Batt14; Hume and Weyers15, and Chertow et al16 equations were calculated. All patients were followed for at least one year from the time of BIA testing or the point of censoring. The duration of follow-up ranged from 2 days to 18 months. Patients whose survival time was unknown or uninterpretable (N = 19, 0.6%) were excluded from the analysis.

Statistical analysis
Linear correlation among variables was described with the Pearson product moment coefficient. In addition, continuous variables were ranked into quintiles, and the unadjusted means within quintiles were compared using analysis of variance. Pairwise comparisons between the quintile means were performed using the Student–Newman–Keuls procedure17. Adjusted means within quintiles were calculated using the method of least squares. Polynomial transformations of the URR, the urea volume-indexed clearance time product (Kt/V), and the clearance time product (Kt) were performed to examine curvilinear trends with survival.

Covariates were selected a priori and included age, gender, race, diabetes, and vintage ("case mix"), along with Quetèlet's index, phase angle by BIA, and serum concentrations of albumin, prealbumin, creatinine, and ferritin ("nutritional variables"). Variables with significant associations with the relative risk (RR) of death on univariate screening were considered candidates for multivariable modeling. Factors not included in multivariable regression models were re-entered individually to evaluate for residual confounding (>5% change in URR or URR2 or Kt parameter estimate). Multivariable regression was performed using the proportional hazards model, with variable entry and exit criteria set at the P = 0.05 level18. Plots of log [-log (survival rate)] against log (survival time) were performed to establish the validity of the proportionality assumption19. Multiplicative interaction terms were tested to explore interaction among dialysis dose and selected explanatory variables. Unadjusted and multivariable RRs and 95% confidence intervals (95% CI) were calculated based on model parameter coefficients and standard errors, respectively. Patients who underwent kidney transplantation (N = 82, 2.7%), recovered renal function (N = 18, 0.6%), transferred dialysis facilities (N = 287, 9.7%), withdrew from dialysis (N = 42, 1.3%), or were lost to follow-up for unknown reasons (N = 8, 0.3%) were censored. Two-tailed P values of less than 0.05 were considered statistically significant. Statistical analyses were conducted using SAS 6.08 (SAS Institute, Cary, NC, USA).

Top of pageRESULTS
The mean age was 60.5 15.5 years. The dialysis vintage was 3.8 3.7 years (median 2.6 years, range <1 to 27.3 years), and 47.2% of patients were women. The distribution of race was black (46.9%), white (45.4%), Hispanic (6.5%), and other (1.2%). The mean URR was 65.6 7.0%. The mean URR values within quintiles 1 through 5 were 55.2, 62.3, 65.8, 69.1, and 74.4%. The mean Kt/V was 1.08 0.21. The mean corresponding Kt/V values were 0.81, 0.96, 1.07, 1.17, and 1.37.

There was a direct correlation between URR and age (r = 0.16, P < 0.0001) and between URR and hemodialysis vintage (r = 0.11, P < 0.0001). Higher order terms of age and vintage were also statistically significant, indicating more complex relationships among these variables and URR. The proportion of women was higher with increasing URR (29.5, 38.1, 43.3, 56.3, and 68.5% in quintiles 1 through 5, P < 0.0001). The proportion of black patients was lower with increasing URR (60.4, 52.2, 43.2, 42.3, and 38.1% in quintiles 1 through 5, P < 0.0001), as was the proportion of patients with diabetes mellitus (41.8, 40.6, 36.9, 33.4, and 31.0% in quintiles 1 through 5, P < 0.0001).

Urea reduction ratio and indicators of nutritional status
There were no linear correlations between serum albumin (r = -0.01, P = 0.64) or serum prealbumin (r = 0.04, P = 0.08) and URR. Nevertheless, there were significant curvilinear associations among these variables, as shown in Table 1. Comparing the mean serum albumin and prealbumin concentrations among the quintiles, there were reverse U-shaped relationships between both serum albumin and prealbumin and the URR. To confirm the structure of the albumin–URR relationship, we fit a linear regression equation using URR as the dependent variable, with albumin and albumin squared as independent variables. The model was statistically significant (P < 0.0001) with a significant positive coefficient for the linear term (17.9 3.8, P < 0.0001) and a significant negative coefficient for the quadratic term (-2.4 0.5, P < 0.0001), confirming the reverse U-shaped relationship. The relationship between URR and prealbumin was of borderline statistical significance (P = 0.06), with a similar linear and quadratic variable pattern. Higher URR values were associated with lower body weights. Higher URR values were also associated with higher Quetèlet's (body mass) index.

Table 1 - Means of nutritional and related indicators stratified by quintiles of urea reduction ratio (URR).Full table

Among the bioimpedance parameters, we examined the relationship between URR and phase angle. Phase angle has been observed to be a valid indicator of nutritional status and predictor of mortal risk in patients with ESRD20,21. There was a significant inverse relationship between phase angle and URR. Because urea distribution volume, which approximates total body water (V), is part of the Kt/V equation, we would expect a significant relationship between the two parameters Table 2. A striking difference in total body water estimates was observed across URR quintiles. To generalize these findings to populations in whom BIA may not be available, Table 3 provides mean total body water estimates within each URR quintile for each of three regression equations: the Watson formula17, the Hume-Weyer formula18, and the formula that was derived elsewhere using these data19. Although the Watson and Hume-Weyer formulae consistently yielded lower estimates than the Chertow et al equation or BIA, the estimates of total body water were uniformly lower among patients with higher URR.

Table 2 - Means of nutritional and related indicators stratified by quintiles of Kt.Full table

Table 3 - Mean total body water estimates (in kg) stratified by URR quintile.Full table

In an effort to incorporate the inflammatory component affecting nutritional status, we explored the relationship between URR and ferritin, a marker of the acute-phase response22. There was a significant difference in serum ferritin concentration across URR quintiles. These findings remained significant after adjustment for the hemoglobin and serum iron concentrations (P < 0.0001). Indeed, 12% of patients in quintile 5 had serum ferritin concentrations in excess of 1000 g/liter compared with 7% or less in the other quintiles (P < 0.0001).

To be certain that the trends in nutritional status across URR quintiles were not confounded by demographic factors, we simultaneously adjusted the means for age, gender, race, and diabetic status. For each parameter, the adjusted means were significantly different across URR quintiles, in the same pattern as noted earlier in this article (reverse U shape for albumin and prealbumin and linear relationships in other cases; data not shown).

Urea reduction ratio, Kt/V and Kt and survival
There was a significant relationship between URR and mortality Figure 1. Using the third quintile of URR as the referent category, the unadjusted RRs and 95% CI across URR quintiles were 1.27 (0.92 to 1.75), 1.10 (0.79 to 1.53), 1.00, 1.04 (0.74 to 1.44), and 1.19 (0.86 to 1.64). To test the structure of the URR–mortality relationship, we fit a companion model using URR and URR2 as continuous variables. A negative coefficient for the linear term (-1.98 10-1, P < 0.0001) and a positive coefficient for the quadratic term (1.47 10-3, P = 0.0002) confirmed the reverse J shape of the URR–mortality curve. The adjusted RR estimates for the URR quintiles were similar whether adjustment was limited to demographic factors (age, gender, race) or demographic and other nutritional variables (phase angle and the serum concentrations of albumin, creatinine, and ferritin) that were independently associated with the RR of death. Vintage, diabetes, and Quetèlet's index did not meet the pre-specified criteria for model inclusion. The multivariable RRs and 95% CI across URR quintiles were 1.67 (1.17 to 2.38), 1.34 (0.94 to 1.91), 1.00, 1.12 (0.78 to 1.61), and 1.12 (0.79 to 1.60). In companion multivariable models treating URR as a continuous variable, the adjusted linear (-1.83 10-1, P = 0.01) and quadratic (1.22 10-3, P = 0.03) terms remained statistically significant. Case mix and nutritional indicators did not influence the association between URR and mortality (multiplicative interaction terms not significant, P > 0.20 for all cases).

Figure 1.Relative risk of death by urea reduction ratio (URR) quintile. Symbols are: () unadjusted RR; () RR adjusted for case-mix (age, gender, and race); () RR adjusted for case mix and nutritional variables. The quintiles of URR correspond to the following values: Q1 (<60.0%), Q2 (60.0 to 64.1%), Q3 (64.1 to 67.4%), Q4 (67.4 to 71.0%), Q5 (>71.0%).

Full figure and legend (18K)

To explore whether the relationship between URR and mortality was dependent on the total body water, URR was converted to a single-pool Kt/V (spKt/V) and then the spKt/V multiplied by V estimated by BIA to derive a clearance time product (Kt, in L). The mean Kt was 42.8 liters. The mean Kt values were 31.0, 38.0, 42.5, 47.6, and 57.2 l in quintiles 1 through 5. There was incomplete overlap of the URR or Kt/V and Kt groups. The mean URR within Kt quintiles was 60.9, 65.0, 65.6, 66.9, and 68.5%, and the mean corresponding Kt/V was 0.96, 1.06, 1.08, 1.12, and 1.18.

There was a significant relationship between Kt and mortality, with a RR of 0.98 (0.97 to 0.99) per liter Kt increase (P = 0.0004). In other words, the linear effect estimate was a 2% decrease in risk per liter clearance increase. There was no evidence of a reverse J-shaped relationship between Kt and mortality Figure 2. Using the third quintile of Kt as the referent category, the RR of death declined with increasing Kt: 1.34 (0.99 to 1.81), 1.06 (0.76 to 1.45), 1.00, 1.00 (0.72 to 1.38), and 0.83 (0.59 to 1.16). Adjustment for age, gender, and race yielded slightly modified RR estimates: 1.47 (1.07 to 2.02), 1.14 (0.82 to 1.58), 1.00, 0.98 (0.71 to 1.36), and 0.85 (0.60 to 1.21). Further adjustment for phase angle and laboratory variables extinguished the trend toward a reduced RR of death in fifth Kt quintile: 1.39 (0.99 to 1.95), 1.19 (0.84 to 1.68), 1.00, 1.02 (0.72 to 1.45), and 0.98 (0.68 to 1.41). There were no significant interactions between Kt and case mix or nutritional variables (multiplicative interaction terms not significant, P > 0.20 for all cases).

Figure 2.Relative risk of death by the clearance time (Kt) quintile. Symbols are: () unadjusted RR; () RR adjusted for case-mix (age, gender, and race); () RR adjusted for case mix and nutritional variables. The quintiles of Kt correspond to the following values: Q1 (<35.5 liters), Q2 (35.5 to 40.0 liter), Q3 (40.0 to 44.8 liters), Q4 (44.8 to 50.7 liters), Q5 (>50.7 liters).

Full figure and legend (17K)

Table 2 shows the means of nutritional variables by Kt quintiles. In contrast to the URR quintile data, patients who received a larger Kt (that is, more liters of clearance) tended to have better nutritional status by the parameters measured. The direct relationship between Kt and serum creatinine is most noteworthy because more clearance would have been expected to lower the steady-state serum creatinine concentration.

Top of pageDISCUSSION
A detailed analysis of the NCDS study and several observational studies that followed it in time have established a relationship between URR or Kt/V and outcomes in hemodialysis patients. In spite of considerable progress, we have failed to identify the optimal dose of dialysis8. Because of aggressive, national continuous quality improvement efforts, a steady increase in the average prescribed and delivered dialysis dose has been observed, such that the majority of patients now achieve URR 65%, and Kt/V 1.223. This success has been achieved by the use of larger surface area dialyzers, higher blood and dialysate flows, and increased dialysis time. Because Kt is actionable, this has been the principle focus of the intellectual analysis of urea kinetics and hemodialysis outcomes.

Although V influences the rate at which the urea nitrogen concentration changes during hemodialysis and in the interdialytic period, V has been shown to correlate directly with several laboratory indicators of nutritional status, including serum creatinine, albumin, and prealbumin24,25. The inclusion of V in the reporting of hemodialysis as a method of indexing dialysis adequacy across patients of different size introduces a nutritional variable into the clearance equation, making relationships between clearance and most outcomes of interest more difficult to interpret.

Herein, we describe the results of a cohort study, unique in its inclusion of estimates of body composition, including total body water. URR was inversely correlated with total body water, whether estimated by BIA or one of three published regression equations. URR was directly correlated with age and dialysis vintage, most likely via the age/vintage–total body water association. That is, with normal aging, there is a decrease in muscle mass and total body water26; this decline may accelerate among persons with chronic disease, including ESRD16. The relationships among albumin, prealbumin, and URR were complex; albeit small in magnitude, we believe that they reflect the intricate interplay between uremia and malnutrition. The direct relationship between URR and Quetèlet's index was not unexpected. Quetèlet's index as a nutritional parameter has numerous limitations and, at best, reflects obesity rather than body cell mass (hence, the misnomer "body mass index").

The relationship between URR and mortality was carefully examined in two ways: first, ranking patients by URR into quintiles and comparing the RR of death within each quintile, and second, examining URR and polynomial transformations of URR as continuous variables in companion models. Although the RR of death in quintile 1 was significantly different than in quintile 3 and other differences were not individually statistically significant, the more powerful models employing continuous variables confirmed the reverse J-shape trend. Patients in the fifth quintile had the greatest URR (mean URR 74.4%, 10%, 90% range 71.5%, 78.3%), but experienced a mortality hazard that was 19% greater than patients in the third quintile (mean URR 65.8%, 10%, 90% range 64.5%, 67.1%). Both quantities of hemodialysis exceed the minimum recommended by evidence-based clinical practice guidelines8.

There are several potential mechanisms for these findings. First, some patients who were small in stature may receive amounts of solute clearance that exceed their metabolic needs. Transient plasma depletion of electrolytes, such as potassium and magnesium, or excessive repletion of solutes such as bicarbonate and calcium could provoke fatal arrhythmia. This contention ("overdialysis") cannot be confirmed nor refuted. Nevertheless, it may be difficult to differentiate electrolyte depletion from protein-calorie malnutrition because they often coexist in patients with overt muscle wasting. Although the predialysis bicarbonate concentration was significantly greater in patients with higher URR (mean 19.9, 20.2, 20.3, 20.5, and 20.8, in quintiles 1 through 5, respectively, P < 0.0001), it is unlikely that this modest difference was associated with a substantial variation in the degree of postdialysis alkalemia. There was no difference in predialysis potassium concentration across URR quintiles (P = 0.13). No postdialysis blood tests were drawn except for the blood urea nitrogen (BUN).

Second, depending on the timing of the postdialysis BUN sample, the URR may variably reflect the equilibrated urea clearance27. The magnitude of urea rebound is directly related to K and inversely related to V. Indeed, patients with the shortest treatment times and greatest URR tend to experience the largest degree of urea rebound8,28. Although the average amount of urea rebound is approximately 0.2 Kt/V, this quantity may be as great as 0.6 Kt/V for some patients. Therefore, some fraction of the patients in quintile 5 with a high URR might have experienced sufficient urea rebound such that the overall equilibrated Kt/V was inadequate. We are unable to either validate or dispute this claim.

There is strong evidence that patients in the fifth quintile of URR suffered from more severe protein-calorie malnutrition than patients in the first four quintiles, the third (and our favored) hypothesis. (Since the incidence of protein calorie malnutrition in patients with ESRD may exceed 50%, it would be unfair and likely inaccurate to surmise that patients in quintiles 1 through 4 were well nourished.) In addition to the data presented in Table 1, the adjusted mean values of nutritional indicators (adjusted for age, gender, race, and diabetic status) were significantly different across URR quintiles, confirming that the differences in albumin, prealbumin, body weight, phase angle, and so forth, were not explained by differences in the demographics of the high URR group. Furthermore, when comparing an index of dialysis dose that was independent of V (the clearance time product), there was no increase in risk as dose increased. Moreover, nutritional status was better in patients with higher Kt Table 2.

Although nephrologists may have made a concerted effort to provide larger hemodialysis doses to patients with lower levels of albumin, prealbumin, and creatinine (older patients, lighter in weight, of longer vintage, more likely white and diabetic) as a strategy to improve their nutritional status, this is unlikely29. The practice of most nephrologists has been to provide smaller surface area dialyzers and shorter dialysis times to patients of smaller body size and vice versa10. Residual confounding and selection bias might explain a fraction of the apparent adverse effect of high URR but are unlikely to account for the consistent inverse relationships between URR and nutritional indicators.

There are several important limitations to our analysis. Although uniform instructions for postdialysis urea collection were provided to all participating units, there were no processes in place to guarantee that these guidelines were followed27. The estimates of Kt/V were based on single-pool assumptions of urea kinetics that do not account for intradialytic urea generation, convective urea clearance, and postdialysis urea rebound8. Furthermore, there were no measurements of residual renal function, which could contribute to total clearance in some patients. Although these approximations could easily affect the precision of the RR estimates, we do not believe that they would change the qualitative conclusions of the analysis.

In summary, using a cohort of patients in whom a direct estimate of total body water was obtained using BIA, we showed significant differences in the concentrations of biochemical and bioelectrical correlates of nutritional status across the spectrum of URR values, although in some cases, these relationships were curvilinear. We showed a reverse J-shaped curve between dialysis dose and survival that was straightened when the dose was no longer indexed to V. These findings suggest that the increase in mortality observed among individuals with very high levels of URR or Kt/V reflects competing risks of protein–calorie malnutrition, rather than excessive dialysis. Identification of patients who achieve extremely high URR (>75%) or single-pooled Kt/V (>1.6) values using standard dialysis prescriptions should prompt a careful assessment of nutritional status. Confounding by protein–calorie malnutrition may limit the utility of URR or Kt/V as a population-based measure of dialysis dose. Therefore, other models of urea kinetics should be considered, such as the clearance time product (Kt). Kt should be prospectively evaluated as an alternative index of dialysis adequacy.

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This was presented as a free communication at the 30th Annual Meeting of the American Society of Nephrology, November 2–5, 1997, San Antonio, Texas, USA.