Abstract
BackgroundProteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria however, some patients may have slow decline of renal function despite lower level of urinary protein excretion. The different mechanical (visco-elastic) and chemical properties, as well as the proteome profiles of urinary proteins might explain their tubular toxicity mechanism. Brillouin light scattering (BLS) and surface enhanced Raman scattering (SERS) spectroscopies are non-contact, laser optical-based techniques providing visco-elastic and chemical property information of probed human biofluids. We proposed to study and compare these properties of urinary proteins using BLS and SERS spectroscopies in nephrotic patient and validate hybrid BLS-SERS spectroscopy in diagnostic of urinary proteins as well as their profiling. The project ultimately aims for the development of an optical spectroscopic sensor for rapid, non-contact monitoring of urine samples from patients in clinical settings.MethodsBLS and SERS spectroscopies will be used for non-contact assessment of urinary proteins in proteinuric patients and healthy subjects and will be cross-validated by Liquid Chromatography-Mass Spectrometry (LC-MS). Participants will be followed-up during the 1 year and all adverse events such as exacerbation of proteinuria, progression of CKD, complications of nephrotic syndrome, disease relapse rate and inefficacy of treatment regimen will be registered referencing incident dates. Associations between urinary protein profiles (obtained from BLS and SERS as well as LC-MS) and adverse outcomes will be evaluated to identify most unfavored protein profiles.DiscussionThis prospective study is focused on the development of non-contact hybrid BLS - SERS sensing tool and its clinical deployment for diagnosis and prognosis of proteinuria. We will identify the most important types of urine proteins based on their visco-elasticity, amino-acid profile and molecular weight responsible for the most severe cases of proteinuria and progressive renal function decline. We will aim for the developed hybrid BLS - SERS sensor, as a new diagnostic & prognostic tool, to be transferred to other biomedical applications.Trial registrationThe trial has been approved by ClinicalTrials.gov (Trial registration ID NCT04311684). The date of registration was March 17, 2020.
Highlights
Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality
Gaipov et al BMC Nephrology (2020) 21:229 (Continued from previous page). This prospective study is focused on the development of non-contact hybrid Brillouin light scattering (BLS) - surface enhanced Raman scattering (SERS) sensing tool and its clinical deployment for diagnosis and prognosis of proteinuria
We will identify the most important types of urine proteins based on their visco-elasticity, amino-acid profile and molecular weight responsible for the most severe cases of proteinuria and progressive renal function decline
Summary
Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria some patients may have slow decline of renal function despite lower level of urinary protein excretion. The main pathway of progressive renal scarring is caused by tubular toxicity of filtering proteins, so more, the rapid development of end-stage kidney disease (ESKD) is expected in those patients who have higher level of proteinuria [9, 10]. Despite high level of proteinuria, paradoxically, some patients may have slow decline of renal function compared to those patients with lower level of urinary protein excretion This may possibly due to their different mechanical (viscosity, elasticity and compressibility) and chemical properties, as well as the different proteomic structure of the excreting urinary proteins [11]. There is a continuing uncertainty, why severity of renal failure progression could differ between proteinuric patients?
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