Paradoxical clearance of hyaluronan fragments during haemodialysis and haemodiafiltration.

Background: The physiological clearance of hyaluronic acid (HA), a mortality marker in end-stage kidney disease (ESKD) patients, occurs in the liver and in the kidneys and depends on its molecular mass. The aim of this study was to examine the effect of different modes of renal replacement therapy on levels of low- and high-molecular-mass HA (LMWHA and HMWHA, respectively).

Methods: Levels of total plasma HA as well as LMWHA and HMWHA fractions were measured before and after haemodialysis (HD) and haemodiafliltration (HDF) treatments and compared with those in normal controls. Plasma β2-microglobulin was determined to be an independent inflammation marker. The isolated effect of the extracorporeal system on HMWHA fractions was investigated in a separate in vitro study.

Results: In 150 ESKD patients, LMWHA (135 ng/mL) and HMWHA fractions (386 ng/mL) were elevated (P < 0.01), compared with those in 80 healthy persons. The LMWHA fraction remained unchanged both during HD and HDF, whereas the fraction of HMWHA, which is incapable of passing through dialysis membranes, decreased by about 40% (P < 0.05). The concentration of plasma β2-microglobulin correlated with the pro-inflammatory LMWHA (P < 0.0001; r = 0.67) but not with total HA. In vitro dialysis runs suggested that this decrease was not caused by degradation or adsorption of HMWHA fragments.

Conclusions: Our data suggest that the decrease in the high-mass HA level during HD and HDF mirrors a physiological clearance initiated by HD and HDF rather than by physical elimination in the extracorporeal circulation.