Increasing the frequency of hemodialysis increases its efficiency, which causes the popular dialysis yardstick, single-pool Kt/V, to underestimate the dose just as it overestimates the dose of less frequent dialysis. The frequency dependence of hemodialysis can be explained by examining solute kinetics. Several factors, including the logarithmic fall in solute concentration and solute disequilibrium within the patient, account for the improved efficiency of both daily hemodialysis and continuous peritoneal dialysis, but to fully explain the marked difference in clinical targets for dosing peritoneal versus hemodialysis, one must go outside the realm of urea kinetics. Solutes that dialyze easily, such as urea, but diffuse less readily within the patient, require a 2-compartment model to accurately predict their concentration profiles and to measure efficiency. When applied to appropriately selected solutes, the model can account for the difference in clinical targets and can explain the failure of other indices, such as middle molecule clearance, eKt/V, and EKR, to account for the differences. A cumulative toxic effect of these relatively secluded compounds might offer a better explanation of uremic toxicity and an objective rationale for increasing dialysis frequency and time. Simplified methods for measuring the dose of dialysis fall when the patient is treated more often than 3 times per week, but 2 new and independently derived methods that include parameters to account for the improved efficiency have been developed for measuring frequent dialysis. The new expressions of dose as a weekly analog of urea clearance are similar in magnitude and independent of frequency, giving present-day clinicians a choice of methods to compare 2 to 7 treatments per week. The kinetic behavior of solutes removed by dialysis and the new expressions of dose support the subjective improvement reported by patients, many of whom have embraced a transition to more frequent and prolonged hemodialysis. (C) 2001 by the National Kidney Foundation, Inc.
