OBJECTIVES: I. Evaluate whether hemodialysis providing a 2-pool, variable volume urea kinetic
modelling value of 1.05 versus 1.45 reduces mortality and morbidity in patients with end
stage renal disease.
II. Compare the efficacy of high versus low flux dialyzer membranes.
PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified by center,
age, and diabetes prior to dialysis initiation.
Patients are randomly assigned to 1 of 4 groups: moderate dose dialysis, low flux membrane;
high dose dialysis, low flux membrane; moderate dose dialysis, high flux membrane; or high
dose dialysis, high flux membrane. Moderate dose is a target eKt/V of 1.05 and high dose is
1.45. The dose and delivery of dialysis are measured monthly by the equilibrated fractional
clearance of urea (eKt/V) calculated with double pool kinetics.
Patients are dialyzed 3 times a week in the shortest possible time (minimum 2.5 hours),
adjusted for adequate fluid removal. General medical care, protein and calorie intake, and
dialyzer reuse and other aspects of dialysis therapy are standardized. The protocol document
lists approved dialyzers; no unsubstituted cellulosic membranes are permitted.
The intervention phase of this study is 5 years. Patients are followed for survival.
PROTOCOL ENTRY CRITERIA:
- End stage renal disease that requires in-center hemodialysis 3 times/week On
hemodialysis for at least 3 months (6 months following renal transplant)
- No scheduled renal transplant from living donor
- No concurrent intervention studies unless ancillary to this protocol No concurrent
- Hepatic: Albumin at least 2.6 g/dL by nephelometry No cirrhosis with encephalopathy or
- Renal: Urea clearance (interdialytic) no greater than 1.5 mL/min per 35 liters total
- Cardiovascular: No New York Heart Association class IV congestive heart failure
despite maximal therapy No unstable angina No new onset angina No recent exacerbation
of frequency, duration, or severity of angina
- Pulmonary: No chronic pulmonary disease requiring supplemental oxygen
- Other: Not hospitalized in acute or long term care facility at entry No active
malignancy requiring chemotherapy or radiotherapy No AIDS No active systemic
infection, e.g., tuberculosis or fungal infection No mental incompetence or other
contraindication to protocol therapy Not pregnant Geographically available for
treatment at participating institution No more than 20 missed treatments/year