Increased serum aluminum. An independent risk factor for mortality in patients undergoing long-term hemodialysis.

The annual mortality rate among patients receiving long-term hemodialysis has been rising over the past decade. The prevalences of known risk factors such as older age, male sex, duration of dialysis, presence of diabetes, coronary artery disease, or hypertension do not seem to have changed during this time. However, evidence suggests that an increased body aluminum level may have an adverse effect on survival even in the absence of overt aluminum toxic reaction. Therefore, we evaluated the correlation between serum aluminum levels and mortality in 10 646 patients undergoing long-term hemodialysis. Mortalities were 18% higher for patients with serum aluminum levels between 1520 and 2220 nmol/L and progressively increased to 60% higher for patients with aluminum levels above 7410 nmol/L. Serum aluminum level was an important predictor of survival even after other known risk factors had been controlled. These data strongly suggest that patients undergoing long-term hemodialysis should have periodic surveillance of the serum aluminum levels, and in those patients who have plasma levels of 1520 to 2220 nmol/L or higher, one should seriously consider discontinuing aluminum salts and giving therapy to decrease body aluminum level if it is found to be increased.

Comparing the urea reduction ratio and the urea product as outcome-based measures of hemodialysis dose.

The urea reduction ratio (URR) and normalized treatment ratio (Kt/V) are related quantities that have become accepted measures of hemodialysis dose. Recent studies, however, have suggested that they combine two elements, both favorably associated with clinical outcome, as a single ratio. These elements, Kt and V, may offset each other, producing a complex quantity that does not reflect a true relationship between dialysis exposure and clinical outcome. This project explored and compared the associations of the URR and the ¿urea clearance x time¿ product (Kt) with mortality in a large sample of hemodialysis patients (37,108 patients) during 1998. Survival analyses using conventional techniques were the primary analytic tools. The relationship between URR and survival was U-shaped or J-shaped, with greater relative mortality at both extremes of the URR distribution than at its middle. Thus, identifying a threshold for adequate dialysis was not possible unless one considers also a threshold for overdialysis. Conversely, the association between Kt and outcome was much simpler, reflecting progressive improvement over the range of Kt evaluated here. These analyses suggest that such measures as URR and Kt/V are compound and complex, and that a simpler, more direct, measure, such as the Kt, should be considered to describe hemodialysis dose.

Quality-of-life evaluation using Short Form 36: comparison in hemodialysis and peritoneal dialysis patients.

Short Form 36 (SF-36) is a well-documented health-related quality-of-life (HRQOL) instrument consisting of 36 questions compressed into eight scales and two primary dimensions: the physical and mental component scores. This tool was used to evaluate QOL among peritoneal dialysis (PD) and hemodialysis (HD) patients. The results of 16,755 HD and 1,260 PD patients (728 continuous ambulatory PD [CAPD] and 532 continuous cycling PD [CCPD]) completing an SF-36 during 1996 were analyzed. Three analyses of variance were performed, consisting of (1) no adjustment, (2) case mix (age, sex, race, and diabetes), and (3) case mix plus laboratory parameters. PD patients were younger (P < 0.001), a larger fraction were white (P < 0.001), fewer had diabetes (P < 0.001), and had lower serum albumin concentrations (P < 0.001) and higher creatinine, hemoglobin, and white blood cell count values (P < 0.001) than HD patients. Diabetes was present in a larger fraction of CCPD than CAPD patients (P < 0.001). HD and PD patients scored similarly for scales reflecting physical processes. PD patients scored higher for mental processes, but only after statistical adjustment for the laboratory measures. Scores on scales reflecting physical processes were worse, and those reflecting mental processes were better among CCPD than CAPD patients. HD and CAPD scores were similar. CCPD patients perceived themselves as more physically impaired but better adjusted than HD or CAPD patients. These descriptive data show that perception of QOL among PD and HD patients is similar before adjustment, but PD patients score higher for mental processes with adjustment. CCPD patients score worse for physical function and better for mental function than either CAPD or HD patients. We cannot, however, exclude the influence of therapy selection.

Race and diabetes as death risk predictors in hemodialysis patients.

Case mix and laboratory predictors of death risk were evaluated in 17,185 hemodialysis patients. The laboratory variables most closely associated with the increased death risk borne by diabetic patients (relative to non-diabetics) and White patients (relative to non-Whites) were identified. The analyses of laboratory death risk predictors were similar to those previously reported. Serum albumin concentration is the most powerful death risk predictor among all of the variables, both case mix and laboratory. Statistical models including only case mix variables reveal both race (RRWhites = 1.42) and diabetes (RRdiabetes = 1.43) as significant predictors. Adding creatinine, albumin, and BUN concentrations to the model eliminated diabetes as a significant predictor. Creatinine and albumin accounted for most of the change. Adding only creatinine eliminated race. The data suggest that reduced visceral and somatic protein mass and/or metabolism may be important determinants of mortality in dialysis patients. Because differences in the concentrations of creatinine and albumin explain much of the risk associated with being White or diabetic, differences in nutritional status may explain the reduced survival observed in those groups. Therefore, clinicians should not simply accept without question the notion that diabetics and Whites are doomed to inferior survival.

Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.

Logistic regression analysis was applied to a sample of more than 12,000 hemodialysis patients to evaluate the association of various patient descriptors, treatment time (hours/treatment), and various laboratory tests with the probability of death. Advancing age, white race, and diabetes were all associated with a significantly increased risk of death. Short dialysis times were also associated with high death risk before adjustment for the value of laboratory tests. Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. About two thirds of patients had low albumin. These findings suggest that inadequate nutrition may be an important contributing factor to the mortality suffered by hemodialysis patients. The relative risk profiles for other laboratory tests are presented. Among these, low serum creatinine, not high, was associated with high death risk. Both serum albumin concentration and creatinine were directly correlated with treatment time so that high values for both substances were associated with long treatment times. The data suggest that physicians may select patients with high creatinine for more intense dialysis exposure and patients with low creatinine for less intense treatment. In a separate analysis, observed death rates were compared with rates expected on the basis of case mix for these 237 facilities. The data suggest substantial volatility of observed/expected ratios when facility size is small. Nonetheless, a minority of facilities (less than or equal to 2%) may have higher rates than expected when compared with the pool of all patients in this sample. The effect of various laboratory variables on mortality is substantial, while relatively few facilities have observed death rates that exceed their expected values. Therefore, we suggest that strategies designed to improve the overall mortality statistic for dialysis patients in the United States would be better directed toward improving the quality of care for all patients, particularly high-risk patients, within their usual treatment settings rather than trying to identify facilities with high death rate for possible regulatory intervention.

Death risk predictors among peritoneal dialysis and hemodialysis patients: a preliminary comparison.

Variables associated with survival among 1,522 peritoneal dialysis patients and 16,404 hemodialysis patients who received treatment during 1992 were evaluated. Analysis was performed separately for the treatment types and for the combined patient group. In general, the associates of survival appear similar among patients receiving peritoneal or hemodialysis. Important variables appear related to nutrition, acid-base status (which is related to nutrition), and age.

Primary associates of mortality among dialysis patients: trends and reassessment of Kt/V and urea reduction ratio as outcome-based measures of dialysis dose.

Information from a large clinical database was used to construct time trends for the leading associates of mortality among dialysis patients. The changing strengths of association of those measures with mortal risk were also evaluated. Strength did not change in meaningful ways for serum albumin, creatinine, or anion gap concentrations. It declined for the urea reduction ratio (URR), however, as prevalent values of the URR increased. Irrational patterns of association between the URR and other measures suggested reevaluation of the urea kinetic method for prescribing and judging dialysis dose. Two premises on which the urea kinetic equations rest are not valid if the context for their use is clinical outcome instead of predicting blood urea nitrogen (BUN) concentration. Rigorous use of the Kt/V criterion for dialysis dose could lead to clinical judgment errors, particularly underdialysis for small or malnourished persons. Changes for prescribing dose and judging therapy are recommended.

Bioimpedance norms for the hemodialysis population.

More than 3,000 hemodialysis patients were examined with single-frequency bioelectrical impedance analysis (BIA). Distributions of resistance, reactance, phase angle (PA), and estimates of total body water (TBW) and body cell mass (BCM) by BIA were determined, and compared with traditional laboratory markers of nutritional status. Bioimpedance parameters and body composition estimates differed significantly by age, sex, race, and diabetic status. PA and BCM correlated directly with serum creatinine, albumin, and prealbumin concentrations. Population-based norms for bioimpedance parameters and estimates of body composition are provided.

Development of a population-specific regression equation to estimate total body water in hemodialysis patients.

We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).

Prealbumin is as important as albumin in the nutritional assessment of hemodialysis patients.

BACKGROUND: Although serum prealbumin is considered a valid indicator of nutritional status in hemodialysis patients, there is relatively little evidence that its determination is of major prognostic significance. In this study, we aimed to determine the independent association of serum prealbumin with survival in hemodialysis patients, after adjusting for serum albumin and other indicators of protein energy nutritional status. METHODS: Serum prealbumin was measured in more than 1600 maintenance hemodialysis patients. We determined the correlations among prealbumin and other indicators of nutritional status, including serum albumin, and bioimpedance-derived indicators of body composition. The relationship between serum prealbumin and survival was determined using proportional hazards regression. RESULTS: The serum albumin was directly correlated with the serum prealbumin (r = 0.47, P < 0.0001), but still explained <25% of the variability in prealbumin. Prealbumin was inversely related to mortality, with a relative risk reduction of 6% per 1 mg/dL increase in prealbumin, even after adjusting for case mix, serum albumin, and other nutritional indicators. The increase in risk with lower serum prealbumin concentrations was observed whether the serum albumin was high or low. CONCLUSION: In hemodialysis patients, the serum prealbumin provides prognostic value independent of the serum albumin and other established predictors of mortality in this population.

The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients.

Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.

The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

BACKGROUND: Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. METHODS: We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. RESULTS: As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. CONCLUSIONS: Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.

Body weight-for-height relationships predict mortality in maintenance hemodialysis patients.

BACKGROUND: Protein-energy malnutrition is a strong predictor of mortality in maintenance hemodialysis (MHD) patients. This association has generally been described for serum chemistry measures of protein-energy malnutrition. We hypothesized that body weight-for-height relationships also predict survival in MHD patients. METHODS: During the last three months of 1993, data were obtained on 12,965 men and women concerning clinical characteristics (height, postdialysis weight, age, gender, race, and presence or absence of diabetes mellitus) and laboratory measurements (predialysis serum albumin, creatinine and cholesterol, and the urea reduction ratio). Patient survival during the next 12 months was evaluated retrospectively. RESULTS: In comparison to values for normal Americans determined from the National Health and Nutrition Evaluation Survey II data, weight-for-height relationships tended to be slightly lower than normal in African American men and women and Caucasian men undergoing MHD and were normal or slightly greater in the taller Caucasian women. In both men and women, the mortality rate decreased progressively as the patients' weight-for-height increased. MHD patients who weighed more than normal had the lowest mortality rates. After adjustment for clinical characteristics and laboratory measurements, the inverse relationship between mortality rates and weight-for-height percentiles was still highly significant for patients within the lower 50th percentile of body weight-for-height. Serum albumin correlated directly with weight-for-height in patients in the lower 50th percentile of weight-for-height. Serum creatinine and cholesterol correlated directly with weight-for-height in the entire population of men and women. In contrast, the urea reduction ratio was inversely correlated with weight-for-height. CONCLUSIONS: These data indicate that weight-for-height is a strong predictor of 12-month mortality in male and female MHD patients. Multivariate analyses indicate that body weight-for-height is an independent predictor of higher mortality in those patients who are in the lower 50th percentile for this measurement.

Anemia in hemodialysis patients: variables affecting this outcome predictor.

Despite the prevalent use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients. The goal of this study was to evaluate the impact of anemia on patient survival and characterize the determinants of hematopoiesis that may be amenable to therapeutic manipulation to enhance rhEPO responsiveness and reduce death risk. Patient characteristics and laboratory data were collected for 21,899 patients receiving hemodialysis three times per week in dialysis centers throughout the United States in 1993. Hemoglobin concentrations (Hb) < or =80 g/L were associated with a twofold increase in the odds of death (odds ratio = 2.01; P = 0.001) when compared with Hb 100 to 110 g/L. No improvement in the odds of death was afforded for Hb >110 g/L. Using multiple linear regression, variables of rhEPO administration (rhEPO dose and percentage of treatments that rhEPO was administered), variables of iron status (serum iron, transferrin saturation, and ferritin), variables of nutritional status (serum albumin and creatinine concentration), and the dose of dialysis (urea reduction ratio) were found to be significantly associated with hemoglobin concentration (P < 0.001). Age, race, and gender were also found to be significantly associated with hemoglobin concentrations (P < 0.001). From this report, the following conclusions may be made. (1) Anemia may be predictive of an increased risk of mortality in some hemodialysis patients. (2) Hemoglobin concentrations > 110 g/L are not associated with further improvements in the odds of death. (3) Laboratory surrogates of iron stores, nutritional status, and the delivered dose of dialysis are predictive of hemoglobin concentration. Whether manipulation of the factors that improve anemia will also enhance the survival of patients on hemodialysis is unknown and should be evaluated by prospective, interventional studies.

Changing hemodialysis thresholds for optimal survival.

BACKGROUND: The urea reduction ratio (URR), a measure quantitating solute removal during hemodialysis, is the fractional reduction of the blood urea concentration during a single hemodialysis treatment. The URR is the principal measure of hemodialysis dose in the United States. Based on studies of patients dialyzed prior to 1994, a minimum URR value of 65% was recommended to optimize survival. Because of new hemodialysis technologies and evolving demographics of the hemodialysis population, the relationship between the amount of hemodialysis and mortality was examined in contemporary cohorts. METHODS: This retrospective cohort included> 15,000 patients per year receiving hemodialysis during 1994 through 1997. Each patient's URR was averaged for the three months prior to the beginning of each year. Mortality odds ratios were calculated for patients by URR. To determine the URR value above which no further improvement in mortality was seen ("threshold"), spline functions were tested in logistic regression models, both unadjusted and adjusted for case mix measures. The strength of fit for URR, defined by a range of candidate thresholds from 55 to 75%, was evaluated in increments of 1% for each year using spline functions. RESULTS: The median URR was 63.2, 65.4, 67.4, and 68.1% for 1994 through 1997, respectively. The median length of hemodialysis treatments increased only six minutes from the beginning to the end of the period of analysis. Using spline functions, the threshold URR values were 61.1, 65.0, 68.0, and 71.0% for 1994 through 1997 in models adjusted for case mix. The ratio of median URR to URR threshold decreased from 1.03 in 1994 to 0.97 in 1997. CONCLUSIONS: From 1994 to 1997, the median URR and the URR threshold for mortality benefit increased. Although an increased need in the amount of hemodialysis may be a consequence of changes in patients' demographic characteristics, the likely explanation(s) is a change in the dialysis procedure and/or blood sampling favoring higher URR values without changing the amount of dialysis provided. The recommended minimum URR of 65% appears to be too low to confer an optimal mortality benefit in the context of current practices.

Predicting hemodialysis access failure with color flow Doppler ultrasound.

Color flow doppler ultrasound examination of the hemodialysis access was conducted in 2,792 hemodialysis patients to evaluate its value in predicting hemodialysis access failure. After baseline assessment of vascular access function with clinical and laboratory tests including color flow doppler evaluation these patients were followed for a minimal of 6 months or until graft failure occurred (defined as surgery or angioplasty intervention, or graft loss). The patient demographics and vascular accesses were typical of a standard hemodialysis patient population. On the day of the color flow doppler examination systolic and diastolic blood pressure, hematocrit, urea reduction ratio, dialysis blood flow, venous line pressure at a dialysis blood flow of 250 ml/min, and access recirculation rate were measured. At the conclusion of the study 23.5% of the patients had access failure. Case mix predictors for access failure were determined using the Cox Model. Case mix predictors of access failure were race, non-white was higher than white (p < 0.005), younger accesses had a higher risk than older accesses (p < 0.025), accesses with prior thrombosis had a higher risk of failure (p=0.042), polytetrafluoroethylene (PTFE) grafts had a higher risk than native vein fistulae (p < 0.05), loop PTFE grafts had a higher risk than straight PTFE grafts (p < 0.025), and upper arm accesses had a higher risk than forearm accesses (p=0.033). Most significant, however, was decreased access blood flow as measured by color flow doppler (p < 0.0001). The relative risk of graft failure increased 40% when the blood flow in the graft decreased to less than 500 ml/min and the relative risk doubled when the blood flow was less than 300 ml/min. This study has shown that color flow doppler evaluation, quantifying blood flow in a prosthetic graft, can identify those grafts at risk for failure. In contrast, color doppler volume flow in native AV fistulae could not predict fistula survival. This technique is noninvasive, painless, portable, and reproducible. We believe that preemptory repair of an anatomical abnormality in vascular access grafts with decreased blood flow may decrease patient inconvenience, associated morbidity, and associated costs.

The urea [clearance x dialysis time] product (Kt) as an outcome-based measure of hemodialysis dose.

BACKGROUND: The normalized treatment ratio [Kt/V = the ratio of the urea clearance x time product to total body water] and the urea reduction ratio (URR) have become widely accepted measures of dialysis dose. Both are related to and derived from pharmacokinetic models of blood urea concentration during the dialysis cycle. Theoretical reconsideration of the models revealed that the premise about V on which they rest (that is, that V is a passive diluent with no survival-associated properties of its own) is flawed if the intended use of the models is for profiling clinical outcome (for example, mortality) rather than estimating urea concentration. As a proxy for body mass, V has survival-associated properties of its own. Thus, indexing clearance x time to body size could create an offsetting combination whereby one measure favorably associated with survival (Kt) is divided by another (for example, V). Observed clinical paradoxes support that interpretation. For example, patients with a low body mass have both higher URR and higher mortality than heavier patients. Increasing mortality is often observed at high URR, suggesting the possibility of "over-dialysis." Black patients tend to be treated at lower URR than whites but enjoy better survival on dialysis. Therefore, clearance x time was evaluated as an outcome-based measure of dialysis dose, not indexed to V, and various body size estimates were evaluated as separate and distinct measures. METHODS: The retrospective sample included 17,141 black and white hemodialysis patients treated three times per week. Logistic regression analysis was used to evaluate death odds in age-, gender-, race-, and diabetes-adjusted models. Kt and five body size estimates (total body water or V, body weight, body weight adjusted for height, body surface area, and body mass index) were evaluated using two analytical strategies. First, all of the measures were treated as continuous variables to explore different statistical models. Second, Kt and the body size measures were divided into groups to construct risk profiles. RESULTS: All evaluations revealed improving death odds with increasing Kt (whether adjusted for the body size estimates or not) and also with increasing body size (whether adjusted for Kt or not) for each estimate of size. Significant statistical interactions of Kt with gender, but not Kt with race, were observed in all models. There were no statistical interactions, suggesting that higher Kt was routinely required with increasing body size. Separate risk profiles for males and females suggested a higher Kt threshold for males. CONCLUSIONS: The urea clearance x time is a valid outcome-based measure of dialysis dose and is not confounded by indexing it to an estimate of body size, which has outcome-associated properties of its own. Dialysis prescriptions for males and females should be regarded separately, but there appears no need to make a distinction between the races.

Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance.

The current report describes the distributions of selected demographic and biochemical parameters, clearance, and other transport values among patients undergoing peritoneal dialysis (PD) and evaluates the associates of mortality using those values, with and without clearance and peritoneal equilibration test (PET) data. All patients receiving PD on January 1, 1994 were selected (n = 2,686). Patients who switched to another form of dialysis during the study period were removed from the study at the time of therapy change. Working files were constructed from the clinical database to include demographic, laboratory, and outcome data. Laboratory data were available in only 1,603 patients and were used to evaluate the biochemical associates of mortality after merging the biochemical, demographic, and outcome data. Patients with clearance data or PET studies underwent a second analysis to assess the effects of peritoneal and renal clearance on survival. The analysis of demographic and laboratory data confirmed the importance of age and serum albumin concentration as predictors of death. Residual renal function (RRF) was strongly correlated with survival, but peritoneal clearance was not. Several possible explanations for the lack of correlation between peritoneal clearance and survival are discussed. The data suggest that RRF and peritoneal clearance may be separate and not equivalent quantities. Substantial work is required to confirm or refute these findings, because the information is essential to establish the adequate dose of PD in patients with various degrees of RRF.

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 x 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.