Infrared vibrational spectroscopy: a rapid and novel diagnostic and monitoring tool for cystinuria

Abstract

Cystinuria is the commonest inherited cause of nephrolithiasis (~1% in adults; ~6% in children) and is the result of impaired cystine reabsorption in the renal proximal tubule. Cystine is poorly soluble in urine with a solubility of ~1 mM and can readily form microcrystals that lead to cystine stone formation, especially at low urine pH. Diagnosis of cystinuria is made typically by ion-exchange chromatography (IEC) detection and quantitation, which is slow, laboursome and costly. More rapid and frequent monitoring of urinary cystine concentration would significantly improve the diagnosis and clinical management of cystinuria. We used attenuated total reflection - Fourier transform infrared spectroscopy (ATR-FTIR) to detect and quantitate insoluble cystine in 22 cystinuric and 5 healthy control urine samples. Creatinine concentration was also determined by ATR-FTIR to adjust for urinary concentration/dilution. Urine was centrifuged, the insoluble fraction re-suspended in 5 μL water and dried on the ATR prism. Cystine was quantitated using its 1296 cm−1 absorption band and levels matched with parallel measurements made using IEC. ATR-FTIR afforded a rapid and inexpensive method of detecting and quantitating insoluble urinary cystine. This proof-of-concept study provides a basis for developing a high-throughput, cost-effective diagnostic method for cystinuria, and for point-of-care clinical monitoring

Label free detection of sensitive mid-infrared biomarkers of glomerulonephritis in urine using Fourier transform infrared spectroscopy

“…Several studies have reported the application of FTIR to routine clinical chemistry analyses and disease diagnostics in fluids, cells and tissues 24,[29][30][31][32][33] . Along with existing applications in various types of cancer, bone and neurodegenerative diseases [34][35][36] , there are ongoing initiatives to encourage work on infrared based technologies and their wider application to clinical medicine 37 (https://clirspec.org/uk-network/).…”

Label-free molecular imaging of the kidney

“…Oliver et al . 169 developed a novel tool for diagnosis and monitorization based on an IRMS technique called attenuated total reflection FTIR. To quantify cystine in urine samples of patients, the authors had to first quantify creatinine levels in the urine samples, and the levels were then matched with parallel measurements performed using ion exchange chromatography.…”

“…Attenuated total reflection FTIR was shown to be a rapid and inexpensive method for detecting and quantifying insoluble urinary cystine with a view to early diagnosis. 169 …”

Fiber attenuated total reflection infrared spectroscopy of kidney tissue during live surgery

“…IR absorption spectra of biological tissue are rather complex and difficult to analyze; nevertheless, during the last decades, there are many successful attempts to apply IR spectroscopy for detection of tumorous tissue areas [5][6][7][8], for elucidating structure of kidney, bladder or gall stones [9][10][11][12], for analysis of sediments in various bodily fluids [13][14][15]. Main drawback of this method is that sample for the studies has to be transferred from the patient to the instrument.…”