The Ratio of Plasma and Urinary 8-oxo-Gsn Could Be a Novel Evaluation Index for Patients with Chronic Kidney Disease

Received Sep 5, 2017; Accepted Oct 19, 2017

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1. Introduction

Reactive oxygen species (ROS) are persistently generated by living cells under normal physiological conditions as a consequence of cellular metabolism and external environmental factors, such as smoke and ultraviolet radiation. Previous studies have suggested that ROS can damage nucleic acids, lipids, and proteins. DNA and RNA precursor nucleotides are also subjected to oxidative damage. Among the various types of oxidized purine and pyrimidine bases thus produced, guanine has the lowest oxidation potential; it is most readily oxidized to form 8-oxo-7,8-dihydro-2${}^{\prime }$-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn). The damaged nucleosides are produced in the cells, then circulated in the blood, and finally excreted in the urine. Oxidative damage of nucleic acids is a potential mechanism for the development of numerous diseases [1]. Rarely are oxidative products of nucleic acids studied in the field of renal disease, although they have been discussed in regard to diabetic nephropathy [2] or dialysis [3]. Patients in the predialysis group exhibited higher levels of nucleic acid oxidation, while oxidative levels were reduced after dialysis [3]. This revealed the important role of nucleic acid oxidation in renal disease. The study investigated the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD.

CKD, defined by the presence of kidney damage (resulting in proteinuria) or reduced kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²) [4], has become a serious, high-incidence disease that affects human health. According to epidemiology research, approximately 10 to 15% of the entire adult population worldwide have been diagnosed with CKD and it is estimated that CKD will increase to about 33% by 2020 [5–8]. Eventually, most patients will inevitably develop end-stage renal disease (ESRD). It is therefore urgent to find a promising diagnostic method for this disease.

In our research, we applied an accurate method based on isotope dilution ultra high-performance liquid chromatography triple-quadrupole mass spectrometry (UHPLC-MS/MS) to simultaneously assay the concentrations of 8-oxo-dGsn and 8-oxo-Gsn in the plasma and urine of 146 patients with CKD. Our data revealed the relevance of nucleic acid oxidative products in CKD diagnosis and could present...