Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKD

• Published in: Kidney360 Vol. 3; no. 2; pp. 357 - 363
• Main Authors: Lin, Tzu-Ling, Evans, Rhys D R, Unwin, Robert J, Norman, Jill T, Rich, Peter R
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 24.02.2022
• Subjects: Ataxia Telangiectasia Mutated Proteins - analysis; Creatinine - analysis; Humans; Innovative Technology and Methodology; Renal Insufficiency, Chronic - diagnosis; Saliva - chemistry; Spectroscopy, Fourier Transform Infrared - methods; Urea - analysis; saliva; basic science; chronic kidney disease; spectroscopy; Fourier transform infrared; biomarker; CKD; infrared spectroscopy; urea
• DOI: 10.34067/KID.0004362021
• ISSN: 2641-7650

Stages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1-5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1-2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3-5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; <0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3-5 CKD.