Effect of Dose

The first variable to be thoroughly analyzed to account for poor outcomes was dose.  The initial work concentrated on identification of the best solute marker of uremia.  These efforts produced the square meter-hour hypothesis1, based on the notion that toxins of middle molecular weight were mostly responsible for the uremic syndrome and was followed by the more prevalent discipline of urea kinetic modeling, based on urea removal2,3.  Urea is not a recognized uremic toxin, but has been shown to be both a good surrogate for protein intake and a convenient index of dialysis performance.

The mechanistic analysis of the National Cooperative Dialysis Study (NCDS) suggested that while dose was important in improving outcomes, no additional benefits were obtained after a certain level in the range of Kt/V ~ 0.9 to 1.44.  Many years later, the HEMO Study mostly confirmed this finding in a large, controlled and randomized trial with good separation of the treatment arms5.  The dose achieved during the study was eKt/V 1.16 and 1.53 for the two arms, respectively; however, no difference in survival was observed between the two groups, except among women who had a lower mortality associated with the high dose6.


  1. Babb AL, Popovich RP, Christopher TG, Scribner BH.  The genesis of the square meter-hour hypothesis.  Trans Am Soc Artif Intern Organs 17:81-91, 1971
  2. Gotch FA. Kinetic modeling in hemodialysis. In: Nissenson AR, Fine RN, Gentile DE  (Eds).  Clinical Dialysis, 3rd ed.  East Norwalk, CT: Appleton & Lang, 1995;156-188
  3. Gotch FA, Sargent JA, Keen ML.  Wither goest Kt/V? Kidney Int 58 (Suppl 76):S3-S18, 2000
  4. Gotch F, Sargent JA.  A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 28:526-534, 1985
  5. Eknoyan G, Beck GJ, Cheung AK, Daugirdas J, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto RHSG.  Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347:2010-2019, 2002
  6. Depner T, Daugirdas J, Greene T, Allon M, Beck G, Chumlea C, Delmez J, Gotch F, Kusek J, Levin N, Macon E, Milford E, Owen W, Star R, Toto R, Eknoyan G. Dialysis dose and the effect of gender and body size on outcome in the HEMO Study. Kidney Int 65:1386-1394, 2004