Rate of creatinine equilibration in whole blood

Abstract

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.

Mechanism of Prominent Trimethylamine Oxide (TMAO) Accumulation in Hemodialysis Patients

“…TMAO like creatinine displayed a dialytic clearance less than that of urea. In the case of creatinine it is well known that creatinine unlike urea does not exit the red cell in the 15 seconds that the blood transits the dialyzer [ 8 ]. Indeed, red cells are less permeable to urea and uric acid than to urea and uremic ones are even less permeable to creatinine and uric acid than those from normal subjects thereby further limiting their dialytic removal [ 9 , 10 ].…”

Investigating Interferences of a Whole-Blood Point-of-Care Creatinine Analyzer: Comparison to Plasma Enzymatic and Definitive Creatinine Methods in an Acute-Care Setting

“…The RW fraction represents intracellular water volume not occupied by hemoglobin, and it is possible that RW is associated with the volume of intracellular fluid containing metabolites that interfere with the creatinine reagent strips. Alternatively, the reagent strip could osmotically promote movement of water out of red blood cells, leading to dilution of plasma creatinine because zwitterionic creatinine diffuses more slowly than water across red blood cell membranes (26 ). Through either mechanism, a negative interference with the StatSensor creatinine results was observed as the RW fraction increased (see Fig.…”

A swan song for Kt/Vurea

“…In contrast, this resistance is substantial for most other toxins . Even kinetic pattern of solutes with seemingly similar physical characteristics such as creatinine or other guanidines is markedly different from that of urea, and, less surprisingly, the same has been described for several protein‐bound uremic toxins and for the middle molecules, such as β 2 ‐microglobulin . No correlation could be found at multivariate analysis between Kt/V and predialysis concentration of several protein‐bound uremic toxins and β 2 ‐microglobulin, in sharp contrast to the significant correlation of several toxins with residual renal function and/or dietary protein intake …”