Transcellular urea gradients cause minimal depletion of extracellular volume during hemodialysis

Concern exists that increasingly high-efficiency dialysis will result in large urea gradients between intracellular and extracellular compartments (VI, VE) leading to large amounts of extracellular volume depletion (delta VE) and hemodynamic instability induced by rapid water flow from VE to VI. The authors investigated this question with a two-compartment model that provided estimates of VI, VE, and osmotically active intracellular and extracellular urea and nonurea concentrations during hemodialysis. The authors found that the urea gradient-induced transcellular water shift is only a very small fraction of VE, even with high urea clearance and short hemodialysis time. The net water shift was small because the urea and nonurea transcellular osmolar gradients were of similar magnitudes but in offsetting directions.