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 RR 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.

Index Words: Dialysis adequacy, urea kinetic modeling, uremic toxins, erythrocyte, intracellular