title: Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?
abstract: BACKGROUND
  Patients 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.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  Reverse 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.
  
  
  CONCLUSIONS
  Reverse 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.
authors.affiliation: Department of Renal Medicine and Renal Research, Manchester Royal Infirmary, Manchester, UK. leonard.ebah@doctors.org.uk
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Ebah
authors.forename: Ian
authors.initials: I
authors.lastname: Read
authors.forename: Andrew
authors.initials: A
authors.lastname: Sayce
authors.forename: Jane
authors.initials: J
authors.lastname: Morgan
authors.forename: Christopher
authors.initials: C
authors.lastname: Chaloner
authors.forename: Paul
authors.initials: P
authors.lastname: Brenchley
authors.forename: Sandip
authors.initials: S
authors.lastname: Mitra
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood*; D005260:Female; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D006435:Renal Dialysis / Q000379:methods; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis*; D014508:Urea / Q000097:blood*
chemical_list: D015415:Biomarkers; D014508:Urea; D003404:Creatinine