Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products

Silvia Giovanella,Giulia Ligabue,Frank Simonis,Jeroen C. Vollenbroek,Paul J. Besseling,Gianni Cappelli,Karin G. F. Gerritsen,Maria A. Bajo Rubio,Marianne C. Verhaar,Jaap A. Joles,Babette H. Lentferink,Maaike K. Gelder,Diënty H. M. Hazenbrink

doi:10.1111/aor.14040

Abstract

A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO‐based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3‐deoxyglucosone) were measured in EO‐ and non‐EO‐treated fluids. Glyoxal and methylglyoxal concentrations increased 26‐ and 11‐fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209‐ and 353‐fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.

Highlights

The availability of a wearable artificial kidney (WAK) for patients with end-stage kidney disease (ESKD) has been long-awaited
Several miniature artificial kidney devices for HD and peritoneal dialysis (PD) are under development which is based on enzymatic hydrolysis of urea by urease or urea adsorption by activated carbon (AC).[6]
Our study shows that electrochemical dialysate regeneration with the current setup using graphite electrodes combined with AC is not safe due to the formation of glucose degradation products (GDPs) which are not biocompatible

Summary

Introduction

The availability of a wearable artificial kidney (WAK) for patients with end-stage kidney disease (ESKD) has been long-awaited. ELECTROOXIDATION FOR A WEARABLE ARTIFICIAL KIDNEY is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production (240- 470 mmol/d3,4) and is difficult to adsorb.[5] Currently, no efficient urea removal strategy is available that allows for the realization of a WAK 5 kg including the daily amount of sorbents and dialysate) and do not allow for further miniaturization. Electrooxidation (EO) is being explored as an alternative strategy to efficiently remove urea from dialysate.[2]

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