Complex compartmental behavior of small water-soluble uremic retention solutes: Evaluation by direct measurements in plasma and erythrocytes

Background: Although scanty data suggest that large solutes show kinetic behavior different from urea, there are virtually no data comparing the kinetics of urea with those of other small water-soluble uremic compounds, which are believed to behave similarly. Study Design: Cross-sectional study of kinetics of urea and guanidino compounds in plasma and erythrocyte compartments during a single hemodialysis session. Setting & Participants: Six stable hemodialysis patients on standard low-flux dialysis therapy. Predictors: Reduction ratios (RRs) of urea calculated from plasma and erythrocyte concentrations. Outcomes: RRs for guanidino compounds calculated from measurements of both plasma and erythrocyte concentrations. Measurements: Blood samples were collected from the dialyzer inlet and outlet at 0, 5, 15, 30, and 120 minutes and at the end of the session. Plasma and erythrocyte concentrations of urea and guanidino compounds (creatinine [CTN], guanidinosuccinic acid [GSA], guanidinoacetic acid [GAA), guanidine [G], and methylguanidine [MG]) were determined. Results: Postdialysis plasma FIR was higher for GSA (82% +/- 3%) compared with urea (77% +/- 2%; P < 0.01), whereas CTN (69% +/- 4%), GAA (49% +/- 14%), G (55% +/- 7%), and MG (55% +/- 7%) showed smaller RRs (P < 0.01). In erythrocytes, GSA (45% +/- 1%), G (10% +/- 13%), and MG (27% +/- 10%) showed markedly smaller RRs than urea (59% +/- 6%; P < 0.05). Finally, significant differences were found between plasma and erythrocyte RRs for urea, GSA, G, and MG (P < 0.01). Limitations: Discrepancies were found between the biochemical and mathematical approaches. Hence, the erythrocyte compartment does not necessarily conform to the kinetic nonperfused compartment. Conclusions: Our data indicate by means of direct estimations that the compartmental behaviors of guanidino compounds and urea are substantially different. Hence, we should consider that not all changes in concentrations in uremia and dialysis are representatively reflected by urea kinetics, even when considering other small water-soluble substances, such as the guanidino compounds. Am J Kidney Dis 50:279-288. (c) 2007 by the National Kidney Foundation, Inc.