R&D Areas | Nephrology | Uraemic Syndrome

Here we examine the use of capillary electrophoresis (CE) coupled to mass spectrometry (MS) to study polypeptide patterns in dialysate obtained during treatment of patients with end stage renal disease. A major complication in dialysis is the uraemic syndrome, which results in the functional failure of vital organs, attributable to the retention of compounds (“uraemic toxins”) that under normal conditions are excreted into the urine by the healthy kidneys. To reduce morbidity and mortality in dialysis the mechanisms for complete removal of uremic toxins are of great interest.

In a recent study the CE-MS method was applied for the identification of a large amount of molecules present in ultrafiltrate from uraemic and normal plasma obtained with high-flux or low-flux membranes. Between 500 and more than 1,000 polypeptides with a molecular weight ranging from 800 to 10,000 Da could be detected in individual samples and were identified via their mass and their particular migration time in capillary electrophoresis.

In ultrafiltrate from uraemic plasma 1,394 polypeptides were detected in the high-flux versus 1,046 in the low-flux samples, while in ultrafiltrate from normal plasma 544 polypeptides versus 490 were found in ultrafiltrate from normal plasma obtained from membranes with comparable cut-off. In addition polypeptides above 5 kDa were virtually only detected in the uraemic ultrafiltrate from the high-flux membrane. To demonstrate the feasibility of further characterizing the detected molecules, polypeptides present exclusively in uraemic ultrafiltrate were chosen for sequencing analyses. A 950.6 Da polypeptide was identified as a fragment of the salivary proline-rich protein. A 1,291.8 Da fragment was derived from alpha-fibrinogen.

The data presented here strongly suggest that the application of proteomic approaches such as CE-MS will result in the identification of many more uraemic solutes than those known at present. This could enable the introduction of more direct elimination strategies, since it is possible to obtain an extended appreciation of the removal capacities of particular dialyzer membranes.