Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis

Background: More intensive hemodialysis (HD) regimens (short daily and long thrice-weekly HD) provide potential opportunities for improved patient outcome. An adequate dialysis dose for these regimens cannot be established from the existing literature. Methods: Using computer simulation, we compared conventional HD with short daily HD and long thrice-weekly HD using two dose measures of solute clearance: equivalent renal clearance (EKR) and a generalized standard Kt/V (stdKt/V) for urea, creatinine, vitamin 1312, inulin, and beta(2)-microglobulin. Solute kinetics were simulated using a variable-volume two-compartment mathematical model. Results: Calculated EKR values were greater during short daily HD compared with those during conventional HD by 16.9%, 15.5%, 16.1%, 5.2%, and 2.5% for urea, creatinine, vitamin 1312, inulin, and beta(2)-microglobulin, respectively. Calculated stdKt/V values predicted more substantial increases in dose for all solutes. Increasing the time of dialysis from 4 to 8 hours three times weekly resulted in substantially greater stdKt/V and EKR values compared with both conventional and short daily HD. Solute clearances during short daily HD could be enhanced to approach those during long HD if treatment time was increased or very high surface area dialyzers were used with very high blood flow rates. Conclusion: Dose measures for all molecules larger than urea increase with either increased frequency or, even more so, increased duration of dialysis. Prediction results of these models require confirmation in clinical studies. Furthermore, the relationship between increased dialysis dose and long-term clinical outcome during more intensive HD regimens requires examination in clinical trials.