Exploring the reverse J-shaped curve between urea reduction ratio and mortality (original) (raw)
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American Journal of Kidney Diseases, 1998
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. 1998 by the National Kidney Foundation, Inc.
Separating the Effects of Hemodialysis Dose and Nutrition: In Search of the Optimal Dialysis Dose
Seminars in Dialysis, 2002
The renal community owes Dr. Frank Gotch a great debt for the contributions that he has made to clarify the relationship between urea clearance and the dose of dialysis. With John Sargent he developed the mathematical approach to hemodialysis (1). In his seminal publication he re-analyzed data of the National Cooperative Dialysis Study to establish the association between the theoretically derived Kt/V for urea and clinical outcomes . Although diffusion equations are well understood and are used in many fields of science, Dr. Gotch's persistent and tireless efforts to identify and quantitate the specific aspects of this process in dialysis through formal kinetic modeling, yielding additionally the protein catabolic rate (
Nephrology Dialysis Transplantation, 2012
Background. The recommended parameter of dialysis dose differs between K-DOQI and the European Best Practice Guidelines. It is not well known to what extent an agreement exists between the different parameters, nor if target and delivered dialysis dose are prescribed according to the urea reduction rate (URR), single-pool Kt/V (spKt/V) or equilibrated double-pool Kt/V (eKt/V) and which parameter is most strongly related to mortality. Methods. In 830 haemodialysis patients from the NECO-SAD cohort URR, spKt/V and eKt/V were calculated and compared according to a classification regarding the recommended treatment targets (70%, 1.4 and 1.2, respectively) as well as minimum delivered dialysis dose (65%, 1.2 and 1.05, respectively). Moreover, the relation between treatment dose and survival was assessed using Cox regression analysis. Results. A spKt/V of !1.4 and URR !70% corresponded with eKt/V !1.20 (as reference method) in, respectively, 98.0 and 90.6% of patients. spKt/V of !1.2 and URR !65% corresponded with eKt/V !1.05 in, respectively, 95.5 and 91.2% of patients. Deviations from the reference method were significantly related to differences in urea distribution volume (spKt/V), treatment time (URR) and ultrafiltration volume (URR). The adjusted HR (95% CI) was 0.98 (0.96, 0.99) for URR, 0.51 (0.31, 0.84) for spKt/V and 0.46 (0.30, 0.80) for the eKt/V. Conclusion. The use of URR leads to larger disagreement with the reference method (eKt/V) treatment target as compared to spKt/V. Low urea distribution volume, short treatment time and low ultrafiltration volumes are predictive parameters for overestimation of dialysis dose when utilizing the alternative methods spKt/V and URR instead of eKt/ V. Delivered eKt/V, spKt/V and URR were all positively related to survival.
Reduction in urea distribution volume over time in clinically stable dialysis patients
Kidney International, 2006
We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and K t /V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0713.5 years) completed the study. Baseline end-dialysis body weight (62.4713.7 kg) showed a non-significant 1% reduction during follow-up (À0.672.8 kg; P ¼ 0.175), whereas V significantly decreased from 29.076.8 to 27.476.0 l (À1.673.0 l or 4.5%; P ¼ 0.002). The reduction in V was greater when baseline albumin was lower (P ¼ 0.001) and baseline V was higher (P ¼ 0.005). The single-pool K t /V calculated using baseline V underestimated the actual value by 0.0770.16 (P ¼ 0.008). The slight underestimate of K t /V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.
American Journal of Kidney Diseases, 2000
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 5urea clearance ؋ time6 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.
Relationship between the target dose for hemodialysis adequacy and nutritional assessment
BACKGROUND: Some studies have shown an increased relative risk of death for patients with higher levels of Kt/V, which may be associated with marked malnutrition. OBJECTIVE: The aim of this study was to investigate the relationship between the target dose for hemodialysis adequacy, as measured by Kt/V, and various nutritional parameters in hemodialysis patients. DESIGN: Cross-sectional. SETTINGS: Sakarya University Faculty of Medicine, Turkey between February 2014 and March 2014. PATIENTS AND METHODS: For consecutive patients who met criteria, the following were recorded: nutritional status, dialysis malnutrition score (DMS), the geriatric nutritional risk index (GNRI), serum albumin level, anthropometric measurements, and bioelectrical impedance analysis. Patients were classified into two groups according to the target hemodialysis dose for single-pool Kt/V: patients with spKt/V ≥1.4 and patients with spKt/V <1.4. MAIN OUTCOME MEASURE(S): Association of hemodialysis adequacy by nutritional assessment. RESULTS: The prevalence of malnutrition in 286 patients with target dose hemodialysis (spKt/V ≥ 1.4) was significantly higher according to body mass index (BMI), DMS, and GNRI (P=.001, P=.006, and P=.004, respectively) compared with patients with a lower target dose (spKt/V < 1.4). BMI, biceps skinfolds, mid-arm circumference, calf circumference, fat free mass, and total body water were statistically significantly lower in patients at a higher target dose (spKt/V ≥ 1.4) (P<.001, P=.034, P=.010, P<.001, P<.001, and P<.001 respectively). CONCLUSIONS: Malnutrition was more frequent in chronic hemodialysis patients who received the target hemodialysis. Evaluation of nutritional status in patients at the target hemodialysis dose should be considered. LIMITATIONS: Data collected from a single region; small sample size; cross-sectional design is disadvantageous.
Comparison of alternative methods for scaling dialysis dose
Nephrology Dialysis Transplantation, 2010
Background. Kt/Vurea was established as an index of haemodialysis (HD) adequacy. The use of Vurea as a normalizing factor has been questioned, and alternative parameters such as body weight 0.67 (W 0.67 ), body surface area (BSA), resting energy expenditure (REE), high metabolic rate organ (HMRO) mass, liver size (LV) and more recently, bioelectrical resistance (R), an independent and directly measurable biological parameter, were proposed as alternative methods for scaling dialysis dose. Methods. The present study aimed to prospectively evaluate the predictive power of some demographic, anthropometric, bioelectrical (BIA) and biochemical parameters, of seven scaling parameters, namely Vurea, as derived from the Watson et al. formulae, W 0.67 , BSA, REE, HMRO, LV and R and of eight HD adequacy indices [single-pool variable-volume Kt/Vurea, computed using the Daugirdas equation, its rescaled equivalents (Kt/W 0.67 , Kt/BSA, Kt/ REE, Kt/HMRO, Kt/LV and Kt/R) and Kt] on long-term survival of a cohort of 328 incident white HD patients. All individuals underwent periodical (every 3 months) biochemical evaluations and single-frequency BIA measurements, injecting 800 μA at 50 kHz alternating sinusoidal current with a standard tetrapolar technique. Results. A first Cox regression analysis, testing the predictive power of some demographic, anthropometric, BIA and biochemical parameters, and of the eight HD adequacy indices on long-term survival of the patients, showed that only higher serum creatinine (Scr) levels (P < 0.0001) and lower Kt/R values (P < 0.04) were significant outcome predictors. As Kt was shown not to be an outcome predictor, a second Cox regression analysis, testing the predictive power of the same demographic, anthropometric, BIA and biochemical parameters, and of the seven scaling parameters on longterm survival of the patients, was built. It showed that only higher Scr levels (P < 0.0001) and higher R values (P < 0.04) were significant outcome predictors. Kaplan-Meier survival analyses of the patients stratified into two groups, respectively, according to the first quartile of R values (0.0-467.8 Ohm), the fourth quartile of Kt/R values (98-106 ml/Ohm) and the first quartile of Scr levels (0.0-11.6 mg/dl) showed a significantly higher long-term survival in the groups of patients having R values above the first quartile (P < 0.04), Kt/R values below the fourth quartile (P < 0.03) and Scr levels above the first quartile (P < 0.0001). Conclusions. Kt/R, R and Scr were independent significant predictors of long-term-survival in incident HD patients: R is related to the fluid status, whereas Scr, which reflects the lean body mass, seems to suggest that body composition is more important than body weight and/or body mass index. Further work is required to develop these concepts and to translate them into rigorous outcomebased adequacy targets suitable for clinical usage.
Relationship of dose of hemodialysis and cause-specific mortality
Kidney International, 1996
Relationship of dose of hemodialysis and cause-specific mortality. A number of studies have found a relationship of lower all-cause mortality risk for ESRD patients treated with increasing dose of dialysis. The objective of this study was to determine the relationship of delivered dose of dialysis with cause-specific mortality. Data from the USRDS Case Mix Adequacy Study, which includes a national random sample of hemodialysis patients, were utilized. To minimize the contribution of unmeasured residual renal function, the sample used in this analysis (N = 2479) included only patients on dialysis for one year or more. Cox proportional hazards models, stratified for diabetes, were used to analyze the effect of delivered dose of dialysis (measured and reported by both Kt/V and URR) on major causes of death and withdrawal from dialysis, adjusting for other covariates including demographics, comorbid diseases present at start of study, functional status, laboratory values and other dialysis parameters. Patient follow-up for mortality was censored at the earliest of time of transplantation, 60 days after a switch to peritoneal dialysis or at the time of data abstraction. For each 0.1 higher Kt/V, the adjusted relative risk of death due to coronary artery disease was 9% lower (RR = 0.91, P < 0.05), due to other cardiac causes was 12% lower (RR = 0.88, P < 0.01), due to cerebrovascular disease (CVD) was 14% lower (RR = 0.86, P < 0.05), due to infection was 9% lower (RR 0.91, P = 0.05), and due to other known causes was 6% lower (RR = 0.94, P < 0.05). There was no statistically significant relationship of KtIV and risk of death among patients who died of malignancy(RR = 0.84, P 0.10) or among patients whose death cause was missing (RR = 0.95, P = 0.41). The risk of withdrawal from dialysis prior to death due to any cause was 9% lower (RR = 0.91, P < 0.05) for each 0.1 higher KtIV. The relationships of delivered dose of dialysis, as measured by URR, and cause-specific mortality were essentially similar in relative magnitude and statistical significance as the relationships observed using Kt/V as the measurement of dialysis dose, with the exception that the relationship was less significant for cerebrovascular disease and withdrawal from dialysis. The relationship of dialysis dose with risk of death due to each cause of death category except other cardiac causes and "other" causes appeared to be of greater magnitude and of greater statistical significance among diabetics than non-diabetics. These results indicate that low dose of dialysis is not associated with mortality due to just one isolated cause of death, but rather is due to a number of the major causes of death in this population. This study is consistent with hypotheses that low doses of dialysis may promote atherogenesis, infection, malnutrition and failure to thrive through a variety of pathophysiologic mechanisms. Further study is necessary to confirm these results and to test hypotheses that are developed.