Comparison of Surface-Enhanced Raman Scattering Properties of Serum and Urine for the Detection of Chronic Kidney Disease in Patients

Abstract

Chronic kidney disease (CKD) affects more than 10% of population around the world and is associated with significant morbidity and mortality. In most cases, this disease is developed silently, and it can progress to the end stage renal failure, therefore, early diagnosis becomes critical for initiating effective interventions. Routine diagnosis of CKD requires both blood tests and urinalyses in a clinical laboratory, which are time-consuming with low sensitivity and specificity. Surface-enhanced Raman scattering (SERS) is an emerging method for rapidly assessing kidney function or injury. This study was designed to compare the differences between the SERS properties of serum and urine for easy-and-simple detection of CKD. There were 126 CKD patients (stage 2-5) and 97 healthy individuals enrolled in this study. SERS spectra of both serum and urine samples were acquired by a Raman spectrometer (785 nm excitation). The correlation of chemical parameters of kidney function with the spectra was examined using principal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squares (PLS) analysis. CKD was discriminated from non-CKD controls by PCA-LDA with a sensitivity of 74.6% and a specificity of 93.8% by serum spectra, and 78.0% and 86.0 % by urine spectra, respectively. The integration area under the receiver operating characteristic curve was 0.937 ± 0.015 (p < 0.0001) for the serum and 0.886 ± 0.025 (p < 0.0001) for the urine. The different stages of CKD were separated with the accuracy of 78.0% and 75.4% by serum and urine spectra, respectively. PLS prediction (R2) of serum spectra was 0.8540 for the serum urea (p < 0.001), 0.8536 for the serum creatinine (p < 0.001), and 0.7500 for the eGFR (p < 0.001), whereas the prediction (R2) of urine spectra was 0.7335 for the urine urea (p < 0.001), 0.7901 for the urine creatinine (p < 0.001), 0.4644 for the eGFR (p < 0.001) and 0.6579 for the urine microalbumin (p < 0.001). In conclusion, the accuracy of SERS evaluation of serum and urine samples compared to clinical biochemical variables of CKD diagnosis in this limited number of patients is similar, suggesting that SERS may be used as a rapid and easy-to-use method for early screening of CKD. This finding requires further evaluation in a large cohort study.

The Potential Applications of Raman Spectroscopy in Kidney Diseases

“…Research in the last decades has published several methods based on RS and SERS for the detection of urinary renal biomarkers, including urea peaks at 1004 cm −1 (symmetrical CN stretch) and 1161 cm −1 (attributed to NH 2 modes), creatinine peaks at 608 cm −1 (NCH 3 stretching, CO deformation and ring vibrations), 680 cm −1 (CNH 2 and CO stretching, ring vibrations), 846 cm −1 (CNH 2 deformation and ring vibrations), and 910 cm −1 (C–C–N stretching), glucose peak at 1128 cm −1 (C–O stretching), and protein peaks at 600, 850, 1060, and 1470 cm −1 (disulfide bonds, tyrosine, C–N bonds, and CH 2 and CH 3 angle bending) [ 23 , 24 , 25 , 26 ]. An overview of the most important findings of these studies is presented in Table 1 [ 11 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The applications of RS for the identification of uropathogens, urine crystals, and kidney stones are not included in this review.…”

“…A Chinese study with 126 CKD patients (CKD stages 2–5) and 97 healthy subjects compared the differences in SERS properties of urine [ 37 ]. Three Raman peaks at 640–680, 1006, and 1625–1655 cm −1 were also reported by others [ 39 , 45 ], while the missing peak at 1026/1028 cm −1 was probably too close to the strong peak at 1006 cm −1 .…”

In situ Raman investigation of the phase transition of NaVO2F2 under variable temperature conditions

“…[8][9][10] Furthermore, Raman spectroscopy is also used in medical systems to detect cancer, diseases related to the human nervous system and other diseases. [11][12][13][14][15] However, in situ Raman spectroscopy can more accurately characterize the transformation law of the structural characteristics of the objects. Numerous scholars have used the in situ Raman method to investigate the phase transition process of ceramics, crystals and methane hydrates under different environmental conditions.…”

Raman Spectral Characterization of Urine for Rapid Diagnosis of Acute Kidney Injury

“…There was also a sharp peak of porphyrin (1621 cm ) in the AKI urine samples, which was possibly due to the effect of a metabolic disorder that causes an enzyme deficiency [ 24 ]. The nitrogenous compounds, which were mostly observed as ethanolamine bands at 880 and 1079 cm , were most likely created by the urea cycle’s amino acid metabolism, and higher concentrations were found in the urine of chronic kidney disease patients [ 25 ].…”