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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.

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.

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.

The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor. (Am J Kidney Dis 1998 Dec;32(6 Suppl 4):S105-12)

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.

Proportional hazards analyses assume that the magnitude of mortality risk for a predictor variable remains proportional over time. In a time-dependent model, the explanatory variable violates this assumption, and repeat observations are required to accommodate the change in risk that occurs over time. Using a retrospective cohort design, we tested the following laboratory values for a time-by-covariate interaction: hematocrit (HCT), serum albumin (ALB), and serum creatinine (CR). A random sample of 4,083 hemodialysis patients whose specimens were analyzed in a central laboratory over a 3-year period served as the study group. Using the baseline observation, we discovered significant probability values for the interaction terms TIME*CR (P = 0.013) and TIME*ALB (P < 0.01). The beta coefficient for TIME*HCT was not significant, indicating that the proportional hazard assumption was not violated by this covariate. Based on these results, we fitted a multivariate regression model containing two time-dependent covariates (CR and ALB) using a data structure that incorporated repeat observations of these laboratory values. Patients with high ALB levels experienced the lowest mortality risk. Similarly, serum CR levels were higher in long-term survivors. This analysis verifies the clinical importance of monitoring ALB and CR levels over time and the hazard of using a single laboratory observation to make long-term projections. Additionally, the predictive values of the time-dependent covariates ALB and CR affirm the significance of nutritional approaches directed toward maintaining visceral and somatic protein content throughout renal replacement therapy.

The mortality rate for hemodialysis patients in the United States is higher than in other industrialized countries. Some attribute this to insufficient quantities of prescribed and delivered dialysis. A multicenter study in Dallas dialysis centers (Dallas Nephrology Associates) was begun in 1989 to assess the impact of increasing the delivered quantity of dialysis on mortality in subsequent years. Dialysis dose was measured by urea kinetic modeling. Kt/V, reflecting the fractional volume of body water clearance of urea during a dialysis treatment, was purposefully increased from 1.18 starting in 1989 to 1.46 in 1992. Additionally, the dialysis dose measured by the urea reduction ratio, the fractional reduction of blood urea nitrogen concentration caused by a dialysis treatment, increased from 63.0% to 69.6% between 1990 and 1992. Outcome analytical methods included both crude and standardized mortality rates and mortality ratios standardized to large end-stage renal disease databases at the United States Renal Data System and at National Medical Care, Inc. Crude mortality rates at Dallas Nephrology Associates decreased from 22.5% in 1989 to 18.1% in 1992. In comparison, between 1990 and 1992 the urea reduction ration in National Medical Care facilities increased from 57.1% to 62.5%. During that time crude mortality rates decreased from 21.8% to 19.5%. Crude mortality in the United States remained essentially unchanged in the same time period. By 1992, Dallas Nephrology Associates and National Medical Care had standardized mortality ratios of 0.77 and 0.74, respectively, compared with the US dialysis population, indicating almost 30% fewer observed deaths than expected. Monitoring dialysis dose by urea kinetic modeling or urea reduction ratio are equally effective in predicting improvement in patient survival. Improved survival is possible in the US end-stage renal disease program with greater amounts of dialysis. This strategy can save an estimated 8,000 to 16,000 lives per year.