Properties of Uremic Solutes That Allow Their Effective Control by Hemodialysis.

Abstract

Background: If the GFR falls far enough, uremic symptoms such as anorexia and nausea prompt the initiation of dialysis. Thrice weekly hemodialysis can prevent recurrence of these symptoms even when patients become anuric. To accomplish this it must maintain the plasma levels of the uremic solutes which cause these symptoms lower than they were when dialysis was initiated. This study examined kinetic properties that solutes must possess for hemodialysis to accomplish this. We also sought to identify uremic solutes that possess these properties.

Methods: Mathematical modeling analyzed how a solute's kinetic properties would determine the relation of its level in an anuric dialysis patients to its level when uremic symptoms prompt dialysis initiation. The previously unstudied solute methylurea was assayed by liquid chromatography tandem mass spectrometry (LC/MS/MS) in 13 participants on hemodialysis, 9 participants with advanced CKD, and 10 participants without kidney disease.

Results: Mathematical modeling showed that conventional dialysis can effectively control the plasma levels better than the failing native kidneys only of solutes which have a high dialytic clearance relative to their native kidney clearance and a large volume of distribution. LC/MS/MS measurements showed that methylurea has these properties. The dialytic clearance of methylurea was 255 ± 32 ml/min and its volume of distribution was 1.09 ± 0.25 times the body water volume in hemodialysis patients. The methylurea clearance was lower than the GFR in patients without kidney disease (fractional clearance 0.44 ± 0.19) and patients with advanced CKD (fractional clearance 0.53 ± 0.10). Literature review revealed that urea was the only solute previously known to possess these properties.

Conclusions: A further search for solutes whose properties include a high dialytic clearance, a relatively low native kidney clearance, and a high volume of distribution could help identify solutes that contribute to uremic symptoms.