Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.
BACKGROUND
Although patients with renal failure retain a large variety of solutes, urea is virtually the only currently applied marker for adequacy of dialysis. Only a limited number of other compounds have up until now been investigated regarding their intradialytic kinetics. Scant data suggest that large solutes show a kinetic behavior that is different from urea. The question investigated in this study was whether other small water-soluble solutes, such as some guanidino compounds, show a kinetic behavior comparable or dissimilar to that of urea.


METHODS
This study included 7 stable conventional hemodialysis patients without native kidney function undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet bloodlines immediately before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two-pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V(1)), the total distribution volume (V(tot)), and the intercompartmental clearance (K(12)); solute generation and overall ultrafiltration were determined independently.


RESULTS
No significant differences were observed between V(1) and K(12) for urea (6.4 +/- 3.3 L and 822 +/- 345 mL/min, respectively) and for the guanidino compounds. However, with respect to V(tot), GSA was distributed in a smaller volume (30.6 +/- 4.2 L) compared to urea (42.7 +/- 6.0L) (P < 0.001), while CTN, CT, GAA, G, and MG showed significantly higher volumes (54.0 +/- 5.9 L, 98.0 +/- 52.3 L, 123.8 +/- 66.9 L, 89.7 +/- 21.4 L, 102.6 +/- 33.9 L, respectively; P= 0.004, = 0.033, = 0.003, < 0.001, = 0.001, respectively). These differences resulted in divergent effective solute removal: 67% (urea), 58% (CTN), 42% (CT), 76% (GSA), 37% (GAA), 43% (G), and 42% (MG).


CONCLUSIONS
The kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water-soluble like urea.
Eloot
Sunny
S
Institute Biomedical Technology, Hydraulics Laboratory, Ghent University, Belgium. Sunny.Eloot@UGent.be
Torremans
An
A
De Smet
Rita
R
Marescau
Bart
B
De Wachter
Dirk
D
De Deyn
Peter Paul
PP
Lameire
Norbert
N
Verdonck
Pascal
P
Vanholder
Raymond
R
D000368:Aged; D003404:Creatinine / Q000097:blood; D005260:Female; D006146:Guanidines / Q000032:analysis* / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012995:Solubility; D014508:Urea / Q000032:analysis* / Q000097:blood
D006146:Guanidines; D014508:Urea; D003404:Creatinine