Identification of biomarkers of chronic kidney disease among kidney-derived proteins

Abstract

Background Chronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state. Methods To identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual. Results Proteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate. Conclusion Overall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.

Proteogenomics in Nephrology: A New Frontier in Nephrological Research

“…Proteogenomics has indeed identified several specific protein biomarkers in CKD. Among the most notable is Complement C1q: this protein was identified as a kidney-derived protein that could serve as a potential biomarker for CKD [28]. The researchers measured the amount of C1q in renal influx and efflux blood samples from seven individuals.…”

“…ADMA, by reflecting nitric oxide synthesis inhibition, offers insights into endothelial dysfunction, a common complication in CKD [38][39][40] • Furthermore, the role of microRNAs in CKD is explored, emphasizing their potential as non-invasive biomarkers for disease detection and monitoring. Changes in microRNA profiles have been correlated with CKD progression and response to treatment, illustrating the dynamic nature of gene expression regulation in kidney disease pathogenesis [27,28,30].…”

Stage II of Chronic Kidney Disease—A Tipping Point in Disease Progression?

“…Romanova et al proposed that serum alpha-1-antitrypsin and HSP90B2 are associated with ESRD and might be potential disease biomarkers [ 8 ]. To add, some authors focused their research on advanced CKD kidney derived proteins and proposed several proteins to be used as early plasma biomarkers of CKD, while others aimed to detect pro angiogenic and inflammatory biomarkers [ 9 , 10 , 11 ]. However, these results require verification, since the protein expression changes dramatically over the course of the disease stages, and it could therefore be misleading to estimate early biomarkers according to proteins expressed in ESRD.…”

Linker-Preserved Iron Metal–Organic Framework-Based Lateral Flow Assay for Sensitive Transglutaminase 2 Detection in Urine Through Machine Learning-Assisted Colorimetric Analysis

“…From the practical testing point of view, point-of-care (POC) biomarkers-based tests would aid in reducing the global burden of CKD . Thus, various urinary CKD biomarkers, such as albuminuria, liver-type fatty acid-binding protein, pentraxin-3, and complement component 1q, have been investigated. , Among them, transglutaminase 2 (TGM2) emerged as a valuable CKD biomarker, showing average concentrations of 0.094 ng/mL (0.001 nM) and 3.35 ng/mL (0.042 nM) in the urine samples of healthy individuals and CKD patients, respectively . Given the extremely low abundance of TGM2 in urine, the discovery and development of detection methods capable of measuring this concentration are crucial countermeasures for early-stage CKD screening, especially under resource-limited settings …”