Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?

Abstract

BackgroundPatients with chronic kidney disease (CKD) need regular monitoring, usually by blood urea and creatinine measurements, needing venepuncture, frequent attendances and a healthcare professional, with significant inconvenience. Noninvasive monitoring will potentially simplify and improve monitoring. We tested the potential of transdermal reverse iontophoresis of urea in patients with CKD and healthy controls.MethodsUsing a MIC 2® Iontophoresis Controller, reverse iontophoresis was applied on the forearm of five healthy subjects (controls) and 18 patients with CKD for 3–5 h. Urea extracted at the cathode was measured and compared with plasma urea.ResultsReverse iontophoresis at 250 μA was entirely safe for the duration. Cathodal buffer urea linearly correlated with plasma urea after 2 h (r = 0·82, P < 0·0001), to 3·5 h current application (r = 0·89, P = 0·007). The linear equations y = 0·24x + 1 and y = 0·21x + 4·63 predicted plasma urea (y) from cathodal urea after 2 and 3 h, respectively. Cathodal urea concentration in controls was significantly lower than in patients with CKD after a minimum current application of 2 h (P < 0·0001), with the separation between the two groups becoming more apparent with longer application (P = 0·003). A cathodal urea cut-off of 30 μM gave a sensitivity of 83·3% and positive predictive value of 87% CKD. During haemodialysis, the fall in cathodal urea was able to track that of blood urea.ConclusionReverse iontophoresis is safe, can potentially discriminate patients with CKD and healthy subjects and is able to track blood urea changes on dialysis. Further development of the technology for routine use can lead to an exciting opportunity for its use in diagnostics and monitoring.

Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers

“…Upon application of an electric field in iontophoresis, three contributions to the total flux of the target compound are possible [29]: (i) electromigration, whereby charged species are electrostatically repelled from an electrode of like polarity and attracted to one of the opposite charge [28]; (ii) electroosmosis, which is a net flow of solvent across the skin in the anode-to-cathode direction and results when the electric field is applied across the net negatively-charged skin (pI ~4.0 to 4.5) [28]; and (iii) passive diffusion, which for amino acids is significantly lower relative to electromigration and electroosmosis [30]. This minimally invasive technique has been shown effective for the monitoring of drugs [31], the constituents of natural moisturizing factor (NMF) [32][33][34][35], glucose [36,37], phenylalanine (to diagnose phenylketonuria [38], urea (as a biomarker of chronic kidney disease) [39], and prostaglandin E2 (a molecule associated with cutaneous inflammation) [40]. As most amino acids are zwitterionic at pH 7.4, electroosmosis towards the cathode on the skin surface is the primary mechanism by which they are extracted transdermally in reverse iontophoresis [28,32,34,41].…”

Dermal-fluid-enabled detection platforms for non-invasive ambulatory monitoring

“…This implies that non-invasive urea detection is useful not only for CKD diagnosis but also for assessing dialysis efficiency. 197 The potential of RI for ISF urea detection was explored using a screen-printed potentiometric sensor wherein urease was immobilized on a micro-structured polypyrene (PPy) matrix that displayed excellent linearity in the range of 10–5000 mM with stable performance for up to 40 days. 198 However, calibration was required, and a few subjects experienced tingling sensations and erythema.…”

An overview of non-invasive methods for transcutaneous measurements of glomerular filtration

“…Later, iohexol also proved as a successful transcutaneous marker for RI measurement. Intravenous (IV) bolus injection of iohexol is monitored over 6 hours, and the sample, which is collected by the transdermal patch, is analyzed using UV-HPLC [8,9]. Nevertheless, these methods remain time-consuming and call for a much rapid detection method.…”