Standardized Hemodialysis Prescriptions Promote Inadequate Treatment in Patients with Large Body Mass

Methods

Patients

All consenting adult patients receiving hemodialysis in four outpatient hemodialysis facilities in Brooklyn, New York, were consecutively screened for eligibility.

Inclusion criteria were hemodialysis treatment three times weekly through a surgically created vascular access in the arm for at least 4 months, age 20 years or older, no more than two previous revisions of the current vascular access, absence of infection (fever or leukocytosis), current treatment with recombinant erythropoietin for at least 4 months, and informed written consent. Patients were followed for 16 weeks. The study was approved by the institutional review board of our institution.

Before the study, exclusion criteria were refusal to participate, HIV infection, blood loss at a gastrointestinal or vascular access site, blood transfusion, hospitalization, infection, or missed hemodialysis session in the 10 weeks before study enrollment. During the study, exclusion criteria were blood loss, hospitalization, infection, missed hemodialysis session, early termination of a hemodialysis session, or any change in hemodialysis prescription.

Information collected included age, sex, race, and clinically determined dry body weight at the start of the study; cause and duration of renal failure; prescribed length of hemodialysis; and hemodialyzer urea clearance as stated by the manufacturer. Hemodialysis was done with modified cellulose acetate hollow-fiber hemodialyzers or polysulfone hemodialyzers. Hemodialyzers were not reused.

Standardized Hemodialysis Prescription

We defined standardized hemodialysis prescription as the current practice of prescribing hemodialysis with insufficient attention to body weight.

Urea Reduction Ratio

The urea reduction ratio was calculated by using the following formula: 100 x ([pre-hemodialysis blood urea nitrogen level (BUN) −post-hemodialysis BUN] ÷ pre-hemodialysis BUN). Post-hemodialysis BUN was measured 1 minute after the end of hemodialysis. Urea reduction ratio was measured at the start of the study and at weeks 4, 8, and 12, and a mean value was calculated for each patient.

Statistical Analysis

The univariate association between urea reduction ratio and body weight was assessed by using Spearman correlation analysis. Patients were sorted by body weight into quartiles and coded with indicator variables from 1 to 4, in ascending order. Analysis of variance was used for between-group comparisons of mean urea reduction ratio, prescribed hemodialysis time, and hemodialyzer urea clearance. Tukey tests were used to test for differences between individual means.

Logistic regression analysis was performed with a urea reduction ratio of 65% or less as the outcome variable. Independent variables included body weight quartile, race, sex, and cause of end-stage renal disease (Table 1). Results of logistic regression include odds ratios, 95% CIs, and P values. All P values are two-tailed. Values given are the mean ±SD unless otherwise noted. Computations were done by using SPS software [9].

Results

Of the 214 patients, 118 were men and 96 were women. One hundred seventy-three were black (81%), 26 were white (12%), and 15 were Hispanic (7%). The mean age was 55.6 ± 15.5 years (range, 22 to 86 years). The renal diagnosis was hypertension in 98 patients (45%), diabetes mellitus in 67 (31%), chronic glomerulonephritis in 12 (6%), systemic lupus erythematosus in 6 (3%), autosomal dominant polycystic kidney disease in 3 (2%), obstructive nephropathy in 2 (1%), and unknown in 26 (12%). The mean duration of end-stage renal disease before the study was 52 ± 49 months (range, 4 to 248 months).

Body Weight

The mean dry body weight at the start of the study was 73 ± 20 kg (range, 40 to 196 kg). Body weight ranges were 41 to less than 59 kg in group 1 (n = 54), 59 to 68.2 kg in group 2 (n = 57), more than 68.2 to 81.8 kg in group 3 (n = 51), and more than 81.8 to 196 kg in group 4 (n = 52).

Hemodialysis Prescription

Mean prescribed hemodialysis time for the entire study group was 3.7 ± 0.42 hours (range, 3 to 4.5 hours) three times weekly, and the mean hemodialyzer urea clearance at a blood flow of 200 mL/min was 183 ± 5.8 mL/min (range, 175 to 195 mL/min).

Mean prescribed hemodialysis time differed between the groups (F probability, 0.0001). Prescribed hemodialysis time was longer in group 4 (3.88 ± 0.3 hours) than in group 1 (3.54 ± 0.43 hours) or group 2 (3.51 ± 0.46 hours) (P < 0.05). Urea clearance of the assigned hemodialyzer differed significantly among the groups (F probability, 0.0002). Group 4 (185 ± 5.9 mL/min) and group 3 (184.2 ± 5.46 mL/min) had higher mean hemodialyzer urea clearances than group 1 (181 ± 5.24 mL/min) or group 2 (181.34 ± 5.6 mL/min) (P < 0.05).

Adequacy of Hemodialysis

Inadequate hemodialysis was defined by a urea reduction ratio of 65% or less. The mean urea reduction ratio for the entire study group was 70% ± 7%. The ratio was greater than 65% in 166 patients (78%) and was 65% or less in 48 patients (22%). It was higher in women (72% ± 6%) than in men (67.6% ± 7%) (P < 0.001), although the prescribed hemodialysis time was shorter in women (3.58 ± 0.43 hours) than in men (3.73 ± 0.41 hours) (P = 0.01). Urea reduction ratio was inversely related to body weight (r = −0.47; P = 0.001) (Figure 1).

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Figure 1. Relation between urea reduction ratio and body weight.

The mean urea reduction ratio differed significantly among the groups (F probability, 0.0001). The mean urea reduction ratio was higher in group 1 (74% ± 5.2%) than in group 2 (70% ± 5.7%), group 3 (68% ± 5.8%), or group 4 (66% ± 8.4%) (P < 0.05). Group 2 had a higher mean urea reduction ratio than group 4 (P < 0.05).

When a urea reduction ratio of 65% or less was used as the outcome variable, logistic regression showed that the odds of receiving inadequate hemodialysis were increased 3.5-fold in men (95% CI, 1.53-fold to 8-fold; P = 0.003), 10-fold in group 3 (CI, 2.1-fold to 50.3-fold; P = 0.003), and 13-fold in group 4 (CI, 2.6 to 61.6; P = 0.001) (Table 1).

Discussion

Our key findings are that hemodialysis prescriptions given with insufficient attention to individual variation in body mass increase the likelihood of inadequate hemodialysis with increasing body mass and that risk for inadequate hemodialysis is greater in men than in women. These findings were in the context of statistically significant differences in prescribed treatment times and hemodialyzer sizes. Thus, although clinicians attempted to individualize prescriptions, their attempts were grossly inadequate. Our findings confirm and extend those of Sherman and colleagues [10], who used Kt/V (a mathematical model for quantifying hemodialysis dose) as the index of the adequacy of hemodialysis to assess the relation between body weight and adequacy of hemodialysis.

The mean duration of prescribed hemodialysis in the United States is 3.5 hours three times weekly. Less than 3% of patients receiving hemodialysis receive more than 4 hours three times weekly [11]. The economically forced limitation on prescribing longer dialysis times clearly places persons with large body mass at excess risk for underdialysis. Several investigators and a National Institutes of Health consensus conference panel have reported that for most patients receiving hemodialysis in the United States, hemodialysis is inadequate [3, 7, 12, 13].

Insufficient hemodialysis prescription has been cited as the reason for the difference between the annual mortality rate of patients receiving hemodialysis in the United States (22% to 24%) and in Japan and Europe (10% to 15%), where the average hemodialysis treatment time is 23.5% longer and bigger hemodialyzers are used [3, 12]. Inadequate hemodialysis not only shortens survival but leads to anemia [14, 15], malnutrition [16, 17], functional impairment [18], and frequent hospitalizations that increase health care costs [5, 11]. Other causes of inadequate hemodialysis include faulty vascular access, missed hemodialysis sessions, or early termination of hemodialysis treatment by the patient.

Because inadequate hemodialysis is often undetected unless it is severe and prolonged, primary care physicians involved in the care of patients receiving hemodialysis should recognize their patients' monthly urea reduction ratios: A target ratio of 70% or more is desirable. Our findings indicate that primary care physicians caring for patients with large body mass should also be attentive to the prescribed duration of hemodialysis and the size of the hemodialyzer.

Our study has several limitations. We did not exclude vascular access stenosis, and blood flow (from patient to hemodialyzer) settings or the timing of measurement of BUN concentrations after hemodialysis may vary. We measured the urea reduction ratio four times; these measurements may not reflect the hemodialysis dose during unmonitored hemodialysis sessions. Clinically determined dry body weights may be imprecise, and manufacturer-stated hemodialyzer urea clearances may not be obtained during hemodialysis. Body weight may confound the observed relation between sex and the adequacy of hemodialysis. The higher urea reduction ratio in women may partly reflect sex-based differences in total body water, muscle, and fat content. Whether an increased likelihood of inadequate hemodialysis results in a higher mortality rate for heavier patients than for smaller patients is mere conjecture at this time, but it is worth noting that the mortality rate for women receiving hemodialysis is lower than that for men.

End-stage renal disease is the only major disease for which the cost of care is funded by the government, and the acceptance criteria consist of diagnosis alone. Reimbursement from Medicare for hemodialysis has decreased while labor costs have escalated. This imbalance has been cited as the underlying reason for pervasive inadequate hemodialysis, which is the direct result of short duration of prescribed hemodialysis and use of small hemodialyzers [3]. Furthermore, in the United States, reimbursement for hemodialysis is given per session of hemodialysis. Thus, a 3-hour treatment commands the same reimbursement rate as a 4-hour treatment. This limits the provider's ability to contain costs while enhancing quality of care [19, 20]. The end-stage renal disease program may illustrate some of the potential problems with switching patients who have chronic illnesses to programs that reimburse by capitation. The well-being of some of these patients may be compromised if the actual cost of treating their illness is higher than the amount reimbursed by the third-party payer. Further research is needed to establish the role of economics in inadequate hemodialysis.

Although the National Kidney Foundation recently issued guidelines calling for an increase in prescribed hemodialysis [8], there is no indication that reimbursement for hemodialysis will soon be substantially increased or reconfigured to reflect the length of treatment sessions. Moreover, most hemodialysis in the United States is now being provided by for-profit corporations, and this trend is accelerating. Our findings underscore the need to individualize hemodialysis prescriptions so that they account for body mass as an important variable.

Ms. Mayers, Ms. Matthew, and Ms. Fowler: Department of Nursing, State University of New York Health Science Center, 450 Clarkson Avenue, Brooklyn, NY 11203.

Dr. Homel: The Scientific/Academic Computing Center, State University of New York Health Science Center, 450 Clarkson Avenue, Brooklyn, NY 11203.