Quantitation of Dialysis: Historical Perspective
Authors: Shinaberger James H. 
Published: March 2003

This article is an attempt to provide a historical perspective to the ongoing attempts to quantify dialysis therapy. It is immediately apparent that motivated chemists, physicists, engineers, mathematicians, and other scientists from all over the world have greatly aided this effort. Dialysis, described by Graham in 1861, was furthered by Abel et al. and Hass before World War I. Willem Kolff attempted to evaluate mass removed and Alwall used a solute extraction ratio. However, the concept of “clearance” and “dialysance” awaited the studies of Wolf et al. in 1951. This classic work describes most of the information concerning actual dialyzer performance known today. A. S. Michaels provided the equations leading to the KoA/Ro/A concept in 1966 which only very recently required updating. The interaction of diffusion and convection is complex and was studied by Villarroel in 1977 and recently by Jaffrin. L. W. Henderson studied and described hemofiltration and hemodiafiltration from 1967–1975.

Efforts to relate the patient's outcome to the dialyzer's performance have been difficult and ongoing since 1971; the Babb‐Scribner Square meter‐hour (which included the expression “Kt/V”); the Kopp et al. Liter‐Kilogram concept; 1972 Kjellstrand clearance * time/kg or Liter. A NIH sponsored conference on the Adequacy of Dialysis in Monterey, California in March of 1974 was focused somewhat on the “middle molecule” theory of uremic toxicity, but contained a presentation by Sargent and Gotch on the possibilities of urea kinetic modeling. They developed iterative computer programs to obtain the best estimates of the required variables. At about this same time, Teschan, Ginn et al. published a series of neurofunctional tests and EEG power spectra analyses which most convincingly showed that dialysis two times a week was inadequate, and that dialysis delivered three times a week at urea clearance equal to body water volume was required to normalize these abnormalities: a major contribution!

The National Cooperative Dialysis Study reported in Kidney International, 1983, was either misunderstood or ignored by most practitioners. The mechanistic analysis of the study by Gotch and Sargent appeared in 1985 and indicated that at adequate protein intake a Kt/V >0.8 yielded better patient survival. In 1982 Malchesky reported the Direct Dialysis Quantification (DDQ) based on calculations from the total mass removed in the dialysate. Although cumbersome, it avoids many errors including the effect of hematocrit and other factors on dialyzer clearance and many consider it to be “the gold standard.”

The 1990s were characterized by the development of many simple logarithmic equations to estimateKt/VandeKt/Vsuitable for spreadsheets which could be used for CQI by individual units. These are primarily by J. T. Daugirdas and coworkers, Smye and Tattersall. In 1991 the Urea Reduction Ratio (URR) was introduced by Lowrie, who in 1999 suggested that Kt and V (as indicator of lean body mass) were independent predictors of survival.

Peritoneal dialysis: Although performed before and immediately after World War II, almost all of the basic quantification mechanistics and data are found in the publications of S. T. Boen (1964). New quantifiers, the Mass Transport Area Coefficient (MTAC) or Pyle‐Popovich model, the Henderson‐Nolph, and Garred models, were compared by Waniewski. Gotch announced a PD modeling program which suggested that a weekly PKt/V at 2.1 was needed to supply the same urea removal as a Kt/V of 3.6, but warned that both were sensitive to decreased time.