Lin, T-L; Evans, RDR; Unwin, R; Norman, JT; Rich, PR; (2021) Assessment of measurement of salivary urea by ATR-FTIR spectroscopy to screen for chronic kidney disease. Kidney360 , 2 (12) 10.34067/kid.0004362021.

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Abstract

Stages of chronic kidney disease (CKD) are currently defined by estimated glomerular filtration rates (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 labour-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 6 healthy controls and 20 CKD patients (stages 1-5) were analysed 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 analyser (Spearman's rank correlation coefficient of 0.71; p<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.

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