GFR Measurement Using Transdermal Detection Methodology.

Abstract

Transdermal fluorescence detection of GFR measurement at the point of care with the fluorescent GFR tracer agent relmapirazin was evaluated. Measurement over the entire range of clinically meaningful GFR and the entire range of human skin tones was demonstrated. A linear regression of transdermally derived GFR to plasma-derived GFR yielded an <i>r</i>² of 0.90 and P30 of 91.9%. The well-known accuracy limitations of eGFR currently used in clinical practice present barriers to optimal care for patients with, or at risk of, decreased kidney function. A point-of-care GFR measurement methodology has the potential to address these limitations. We prospectively assessed transdermal detection of the novel fluorescent GFR tracer agent relmapirazin in participants having normal or impaired kidney function across all human skin colors on the Fitzpatrick Skin Scale (FSS). A multicenter study comprising 74 participants with eGFR from normal to stage 4 CKD was performed. Forty-six participants were FSS types 1–3, and 28 were FSS types 4–6. A module containing a light-emitting diode and photodetector to activate and collect transdermal relmapirazin fluorescence was attached adhesively to the upper chest of each participant. Relmapirazin (1.5 mg/kg) was administered by intravenous push, and fluorescence emission was acquired for 12 hours. A two-compartment pharmacokinetic model fit the fluorescent intensity versus time data, and fluorescence clearance rate (FCR) was extracted from the second (terminal) compartment. Plasma relmapirazin concentrations were measured contemporaneously, and the corresponding plasma GFR for each participant was determined. Linear regression analysis was used to compare the FCR with the indexed plasma GFR. Participant age range was 23–80 years, with 59% female. The two-compartment pharmacokinetic behavior was observed in the fluorescence intensity versus time data, and a FCR was successfully deduced for every participant completing the 12-hour study. The FCR versus indexed plasma GFR yielded an excellent correlation over the range of GFR measured and for all skin colors with a <i>r</i>² of 0.90 (95% confidence interval, 0.85 to 0.94). No severe adverse events were reported. Point-of-care transdermal detection of the fluorescent GFR tracer agent relmapirazin was feasible in patients with normal to impaired kidney function and for a range of skin color types. ClinicalTrials.gov, NCT02772276.