TRANSPORT KINETICS OF PSEUDOURIDINE DURING HEMODIALYSIS AND CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

It has been found that the concentrations of pseudouridine in serum of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are higher than those in patients undergoing hemodialysis. We analyzed whether this could be caused by a lower rate of transport in CAPD when compared with hemodialysis. Mass transfer area coefficients (MTCs) for urea, creatinine, uric acid, and pseudouridine were determined in nine patients undergoing hemodialysis as dialyzer clearances and in 14 patients undergoing CAPD during a 4-hour dwell with 2 L dialysate with glucose, 70 mmol/L. The theoretical MTC of pseudouridine (TPSI), calculated by extrapolation to its molecular weight by use of the MTC of urea, creatinine, and uric acid, was higher than the observed MTC of pseudouridine, both in hemodialysis (136 vs 112 ml/min, p < 0.025) and in CAPD (6.9 vs 3.4 ml/min, p < 0.001). The pseudouridine/TPSI MTC ratio was lower during CAPD than during hemodialysis (0.47 vs 0.83, p < 0.0005), indicating a lower level of transport during CAPD. In vitro experiments with nuclear magnetic resonance spectroscopy supported the hypothesis of glucose induced molecular association of pseudouridine. Therefore, dialysate containing 10 mmol/L glucose was compared with that containing 70 mmol/L glucose in eight patients undergoing CAPD. The MTC of pseudouridine was higher during the experiments with dialysate containing 10 mmol/L glucose (3.5 +/- 2.0 ml/min vs 2.7 +/- 1.9 ml/min, p < 0.05). This was also found for the pseudouridine/TPSI MTC ratio (0.61 vs 0.41, p < 0.02) and the pseudouridine/ creatinine MTC ratio (0.33 vs 0.25, p < 0.02), favoring glucose-induced decrease of MTC-pseudouridine. In conclusion, the transport of pseudouridine for hemodialyzer and peritoneum is less than expected on the basis of its molecular weight. The higher serum concentrations of pseudouridine during CAPD con be explained by the lower transport rate when compared with that of hemodialysis. Our findings support the hypothesis of inhibition of pseudouridine transport to the peritoneal cavity by glucose-induced molecular association in the membrane.