Rate of creatinine equilibration in whole blood

The classic assumption that a large fraction of blood creatinine remains sequestered within erythrocytes when blood is dialyzed has been challenged by recent observations where approximately 60% of erythrocyte water appeared accessible to diffusive creatinine transport during a dialyzer transit. This discrepancy provided the motivation to revisit and reanalyze the equilibration of creatinine across the erythrocyte membrane in a series of in vitro studies with normal human blood under erythrocyte loading and unloading conditions at 37 degrees C. The time course of plasma creatinine concentrations measured by a kinetic picric acid assay was analyzed using a 2-compartment model. In 7 experiments, the equilibration constant was 0.052 +/- 0.013/min, corresponding to a mean half-life of 13.8 +/- 2.8 minutes, and comparable for erythrocyte loading and unloading. With these values and with mean dialyzer transit times in the range of 20 seconds the fraction of erythrocyte water accessible to diffusive clearance is in the range of 2%. These results are comparable to what has been measured with radiolabeled markers almost half a century ago. Therefore, when dialyzer outlet concentrations are sampled without equilibration the effective diffusion volume flow rate for creatinine is close to plasma water flow and does not include sizeable fractions of erythrocyte water flow.