Spectral characteristics of urine from patients with end-stage kidney disease analyzed using Raman Chemometric Urinalysis (Rametrix).

Ryan S Senger,Susan Guelich,Pang Du,Emily Baker,Devasmita Dev,Varun Kavuru,Giuseppe Orlando,Austin Gouldin,Lampros Karageorge,Hana Coogan,Tommy Vu,Gabrielle Martinez,John L Robertson,William Carswell,Kristen Merrifield,Ben Agnor,Meaghan Sullivan,Stephanie Lundgren,Caitlin Steen,James L Pirkle ,Allan H Sklar

doi:10.1371/journal.pone.0227281

Ryan S Senger, Susan Guelich + Show 19 more

Open Access

https://doi.org/10.1371/journal.pone.0227281

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Abstract

Raman Chemometric Urinalysis (RametrixTM) was used to discern differences in Raman spectra from (i) 362 urine specimens from patients receiving peritoneal dialysis (PD) therapy for end-stage kidney disease (ESKD), (ii) 395 spent dialysate specimens from those PD therapies, and (iii) 235 urine specimens from healthy human volunteers. RametrixTM analysis includes spectral processing (e.g., truncation, baselining, and vector normalization); principal component analysis (PCA); statistical analyses (ANOVA and pairwise comparisons); discriminant analysis of principal components (DAPC); and testing DAPC models using a leave-one-out build/test validation procedure. Results showed distinct and statistically significant differences between the three types of specimens mentioned above. Further, when introducing “unknown” specimens, RametrixTM was able to identify the type of specimen (as PD patient urine or spent dialysate) with better than 98% accuracy, sensitivity, and specificity. RametrixTM was able to identify “unknown” urine specimens as from PD patients or healthy human volunteers with better than 96% accuracy (with better than 97% sensitivity and 94% specificity). This demonstrates that an entire Raman spectrum of a urine or spent dialysate specimen can be used to determine its identity or the presence of ESKD by the donor.

Highlights

The chemical composition, physical characteristics, and types/amounts of suspended materials in urine change when kidney disease is present [1,2,3,4]
Raman Chemometric Urinalysis (RametrixTM) [5,6,7,8] was used to determine if differences in molecular spectra could be detected in the following specimen types: (i) urine from healthy human volunteers, (ii) urine from patients undergoing peritoneal dialysis (PD) therapy for end-stage kidney disease (ESKD) and (iii) spent dialysate from these patients receiving PD therapy
RametrixTM relies on Raman spectroscopy and a biological region of the spectrum (400–1,800 cm-1) that is composed of spectral signatures of the thousands of molecules known to the urine metabolome [9,10]

Summary

Introduction

The chemical composition, physical characteristics, and types/amounts of suspended materials in urine change when kidney (and systemic) disease is present [1,2,3,4]. Raman Chemometric Urinalysis (RametrixTM) [5,6,7,8] was used to determine if differences in molecular spectra could be detected in the following specimen types: (i) urine from healthy human volunteers, (ii) urine from patients undergoing peritoneal dialysis (PD) therapy for end-stage kidney disease (ESKD) and (iii) spent dialysate from these patients receiving PD therapy. In the past, sophisticated analyses, including mass spectrometry, liquid/gas chromatography, and kinetic nephelometry have been used to detect analytes (i.e., “biomarkers”) in urine associated with metabolism or disease [3,12,13,14,15]. Urine contains byproducts of therapeutics that help clinicians monitor and adjust therapies [16,17] and can indicate environmental and occupational toxin exposure [18]

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