Properties of Uremic Solutes That Allow Their Effective Control by Hemodialysis

Key Points Hemodialysis can relieve uremic symptoms only by lowering the plasma levels of causative solutes below what they were at dialysis initiation. This can happen only when the ratio of a solute's dialytic clearance to the clearance of the failing kidney is very high. Background If 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 to be 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 patient on dialysis to its level when uremic symptoms prompt dialysis initiation. The previously unstudied solute methylurea (MU) was assayed by liquid chromatography tandem mass spectrometry in 13 participants on hemodialysis, nine participants with advanced CKD, and ten 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. Liquid chromatography tandem mass spectrometry measurements showed that MU has these properties. The dialytic clearance of MU was 255±32 ml/min, and its volume of distribution was 1.09±0.25 times the body water volume in patients on hemodialysis. The MU 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). A 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.