The Influence of Dose, Time and Frequency

The frequency, length and dose of HD have empirically evolved during the past four decades.  The relationships among these variables and their influence on clinical outcomes are complex.  Despite the lack of controlled studies and the selection bias inherent to cohorts studied with enhanced or intensified HD prescriptions, this review explores the impact of frequency, length and dose of HD on clinical outcomes.  The experiences with frequent HD make a formidable case for frequent therapies.  The data show that quotidian regimens are associated with the best biochemical profiles, volume and hypertension control and nutritional status, but do not provide the evidence for superior survival when compared to long nocturnal thrice weekly or every other day conventional HD.  The correlation between frequency and clinical outcomes seems evident, but not likely to be linear.  Perhaps the greatest benefits are achieved from the simple avoidance of 48 hours without dialysis.  Considering the additional cost and patient involvement with daily dialysis compared to every other day dialysis, it is logical to include the latter in future controlled studies on the benefits of frequent HD.  In the meantime the clinical use of HD seems justified in order to achieve more physiological therapy, at a reasonable cost with minimal alteration of the patient’s lifestyle.

The HD prescription has gradually evolved during the past half century, reflecting the balance between clinical outcomes, cost and patient acceptance. HD was initially used once weekly with definite improvement in uremic symptoms1.  However, uremic symptoms became more severe 24-36 hours before the next dialysis.  These symptoms, the accumulation of significant extravascular volume and the development of peripheral neuropathy forced a change to a twice weekly schedule2-4.  Further increase in the frequency of dialysis to thrice weekly occurred because of the persistence of neuropathy and a gout-like syndrome5. Thrice weekly HD was eventually accepted and has remained the standard for more than four decades5,6.  Survival has varied widely between countries and even among different groups in the same country or geographic location while frequency remains essentially unchanged.  The poor outcomes with conventional thrice weekly HD have stimulated interest in more frequent sessions and the role of dose, session duration and frequency in determining outcomes7.


  1. Hegstrom RM, Murray JS, Pendras JP, Burnell JM, Scribner BH. Hemodialysis in the treatment of chronic uremia. Trans Am Soc Artif Intern Organs 7:136-152, 1961
  2. Hegstrom RM, Murray JS, Pendras JP, Burnell JM, Scribner BH.  Two year’s experience with periodic hemodialysis in the treatment of chronic uremia.  Trans Am Soc Artif Intern Organs 8:266-277, 1962
  3. Curtis FK, Cole JJ, Fellows BJ, Tyler LL, Scribner BH.  Hemodialysis in the home. Trans Am Soc Artif Intern Organs 11:7-10, 1965
  4. DePalma JR.  Daily hemodialysis: A very old concept. Semin Dial 12:406-409, 1999
  5. Schribner BH, Cole JJ, Ahmad S, Blagg CR.  Why thrice weekly dialysis?  Hemodial Int 8:188-192, 2004
  6. Eschbach JW, Wilson WE, Peoples RW, Wakefield AW, Babb AL, Scribner BH.  Unattended overnight home hemodialysis.  Trans Am Soc Artif Intern Organs 12:346-359, 1966
  7. Diaz-Buxo JA: Beyond thrice-weekly hemodialysis. Hemodial Int 9:309-313, 2005