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Background: Consensus processes using the clinical literature as the primary source for information generally drive projects to draft clinical practice guidelines (CPGs). Most such literature citations describe special projects that are not part of an organized quality management initiative, and the publication/review/consensus process tends to be long. This project describes an initiative to develop and explore a flexible and dedicated data-driven paradigm for deciding new CPGs that could be rapidly responsive to changing medical knowledge and practice. Methods: Candidate Clinical Practice Monitoring Measures (CPMM) were selected using a large, national database according to the natures and strengths of their associations with mortality risk among patients during 1994. Thresholds above or below which risk of death increased were evaluated for each CPMM using risk profile charts and spline functions. The fractions of patients outside of those thresholds in each dialysis unit (the %Var) were determined for the years 1993, 1994, and 1995. A standardized mortality ratio (SMR) was also determined for each year for each facility. The associations between the %Var and SMR were evaluated in several single-variable and multivariable statistical models. Results: Eleven CPMM were selected and evaluated based on their associations with death risk. These included the urea clearance x dialysis time product (Kt); the concentrations of albumin, potassium, phosphate, bicarbonate, hemoglobin, neutrophils, and lymphocytes in the blood; the body weight/height ratio; diastolic blood pressure; and vascular access type. Even though the CPMM were strongly associated with death risk among patients, the %Var were weakly and inconsistently associated with SMR among facilities. Conclusions: The paradigm was flexible, easy to implement, quickly executed, and potentially able to accommodate evolving medical practice assuming the availability of large database systems such as this. The primary associates of death risk were easily identified and the thresholds easily adopted. The SMR and %Var from the CPMM were only weakly associated, however, suggesting that one cannot be reliably predicted from the other. As such, quality management programs should likely monitor both the processes and outcomes of care among dialysis facilities.

Association between prevalent care process measures and facility-specific mortality rates. Background Medical communities often develop practice guidelines recommending certain care processes intended to promote better clinical outcome among patients. Conformance with those guidelines by facilities is then monitored to evaluate care quality, presuming that the process is associated with and can be used reliably to predict clinical outcome. Outcome is often monitored as a facility-specific mortality rate (SMR) standardized to the mix of patients treated, also presuming that inferior outcome implies a suboptimal process. The U.S. Health Care Financing Administration monitors three practice guidelines, called Core Indicators, in dialysis facilities to assist management of its end-stage renal disease program: ( 1 ) patients' hematocrit values should exceed 30 vol%, ( 2 ) the urea reduction ratio (URR) during dialysis should equal or exceed 65%, and ( 3 ) patients' serum albumin concentrations should equal or exceed 3.5 g/dL. Methods The associations of a facility-specific SMR were evaluated with the fractions of hemodialysis patients not conforming to (that is, at variance with) the Core Indicators during three successive years (1993 to 1995) in large numbers of facilities (394, 450, and 498) using one-variable and multivariable statistical models. Three related strategies were used. First, the association of the SMR with the fraction of patients not meeting the guideline was evaluated. Second, each facility was classified by whether its SMR exceeded the 80% confidence interval above 1.0 (worse than 1.0, Group 3), was less than the interval below 1.0 (better than 1.0, Group 1), or was within the interval (Group 2). The fraction of those patients who did not meet the Indicator guidelines was then evaluated in each group. Third, the ability of variance from Indicator guidelines to predict into which of the three SMR groups a facility would be categorized was evaluated. Results SMR was directly correlated with variance from the Indicator guidelines, but the strengths of the associations were weak particularly for the hematocrit (R 2 = 2.2%, 5.6, and 2.2 for each of the 3 years) and URR Indicators (R 2 = 2.6, 0.6, 3.3). It was stronger for the albumin Indicator (R 2 = 11.6, 20.4, 21.8). The fractions of patients falling outside of the Indicator guidelines tended to be higher in the highest SMR group. The groups were not well separated, however, particularly for the hematocrit and URR Indicators, and there was substantial overlap between them. Finally, although the likelihood that a facility would be a member of the high or low SMR group was associated with fractional variance from Core Indicator guidelines, the strengths of association were weak, and the probability that a facility would be a member of the high or low group could not be easily distinguished from the probability that it would be a member of the middle group. Conclusions While there were statistical associations between SMR and the fraction of patients in facilities who were at variance with these guidelines, they were weak and variances from the guidelines could not be used reliably to predict high or low SMR. Such findings do not imply that measures reflecting anemia, dialysis dose, or medical processes that influence serum albumin concentration are irrelevant to the quality of care. They do suggest, however, that more attention needs be paid to these and other associates and causes of mortality among dialysis patients when developing care process indicator guidelines.

Cardiac arrest and sudden death in dialysis units. Background For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented. Methods To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort openface> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities. Results The cardiac arrest rate was 400 out of 5,744,708, corresponding to a rate of 7 per 100,000 hemodialysis sessions. Cardiac arrest was more frequent during Monday dialysis sessions than on other days of the week. Case patients were nearly twice as likely to have been dialyzed against a 0 or 1.0 mEq/L potassium dialysate on the day of cardiac arrest (17.1 vs. 8.8%). Patients who suffered a cardiac arrest were on average older (66.3 ± 12.9 vs. 60.2 ± 15.4 years), more likely to have diabetes (61.8 vs. 46.8%), and more likely to use a catheter for vascular access (34.1 vs. 27.8%) than the general hemodialysis population. Sixteen percent of patients experienced a drop in systolic pressure of 30mm Hg or more prior to the arrest. Thirty-seven percent of patients who suffered cardiac arrest had been hospitalized within the past 30 days. Sixty percent of patients died within 48 hours of the arrest, including 13% while in the dialysis unit. Conclusions Cardiac arrest is a relatively infrequent but devastating complication of hemodialysis. To reduce the risk of adverse cardiac events on hemodialysis, the dialysate prescription should be evaluated and modified on an ongoing basis, especially following hospitalization in high-risk patients.

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.

Vintage, nutritional status, and survival in hemodialysis patients.BackgroundThe link between dialysis “vintage” (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintage and body composition in hemodialysis patients.MethodsWe explored the relationships among vintage, nutritional status, and survival in a 3009 patient cohort of prevalent hemodialysis patients. Body weight, total body water, body cell mass, and phase angle by bioelectrical impedance analysis were the body composition parameters of interest. We examined vintage as an explanatory variable in multiple linear regression analyses (adjusted for age, gender, race, and diabetes) using body composition parameters and biochemical indicators of nutritional status as dependent variables. Proportional hazards regression was used to evaluate the association of vintage and survival with and without adjustment for case mix and laboratory variables.ResultsDialysis vintage was 3.8 ± 3.7 (median 2.6) years. Body composition parameters tended to be lower after dialysis year 2. Linear estimates per year of vintage beyond year 2 include -0.66 kg body wt (P < 0.0001), -0.17 kg total body water (P = 0.0003), -0.14 kg body cell mass (P < 0.0001), and -0.07 degrees phase angle (P < 0.0001). In unadjusted analyses, vintage was not associated with survival, either as a linear or higher order term. The adjustment for case mix yielded a vintage term associated with an increased relative risk (RR) of death (RR 1.04 (95% CI, 1.01 to 1.07 per year). A further adjustment for laboratory data yielded a RR of 1.06 (95% CI, 1.03 to 1.09 per year).ConclusionDialysis vintage is related to nutritional status in hemodialysis patients, with vintage of more than years associated with a significant decline in all measured nutritional parameters. Cross-sectional analyses probably underestimate these effects. A year accrued on dialysis is associated with a 6% increase in the risk of death, all else equal. Longitudinal assessments of nutritional status, including body composition, are required to better understand the natural history of wasting with ESRD and its implications for long-term survival.

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.

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.

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.

Peritoneal dialysis adequacy: A model to assess feasibility with various modalities. Background The current standard of adequacy for peritoneal dialysis (PD) is to provide a weekly normalized urea clearance (Kt/V) of 2.0 or more and a creatinine clearance (C Cr ) of 60 liter/1.73m 2 or more. As native renal function is lost, it is important to determine the effectiveness of the available therapeutic modalities in achieving these goals. Methods A model to assess our ability to provide a weekly Kt/V urea of 2.0 or more and a C Cr of 60 liter/1.73m 2 or more to anuric patients undergoing continuous ambulatory PD (CAPD) and automated PD (PD Plus) was developed. The body surface area (BSA) distribution was obtained from 38,768 patients undergoing dialysis during January 1997. The distribution of peritoneal transport rates (PTRs) was obtained from 2531 peritoneal equilibration tests performed during 1996. The weekly K p t/V urea was calculated for the various PTR groups and the range of BSA with four PD prescriptions: CAPD 8 liters, CAPD 10 liters, PD Plus 12 liters, and PD Plus 15 liters, using a previously validated kinetic program (PackPD). Results The predicted percentage of patients capable of achieving the adequacy goals for Kt/V and C Cr , respectively, were 24.8 and 11.2 for CAPD 8 liters, 54.2 and 33.0 for CAPD 10 liters, 77.8 and 54.9 for PD Plus 12 liters, and 93.2 and 72.9 for PD Plus 15 liters. Conclusions Most patients can attain the current adequacy standards of therapy with automated PD, but few (less than 25%) can do so with standard CAPD in the absence of residual renal function.

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).

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.

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. Mortallities 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. ( Arch Intern Med . 1991;151:319-322)

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.

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.