Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review

Abstract

Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms “marker *” OR biomarker * AND “renal disease” OR “kidney disease” AND “proteome *” OR “peptid *” AND “urin *”. English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers.

Value of Urinary Transferrin, Urinary Ceruloplasmin and Urinary Neutrophil Gelatinase Associated Lipocalin as biomarkers in Pediatric Lupus Nephritis

“…TF, CP and NGAL were isolated in the urine of pediatric patients with active LN, using proteomics studies. 7,16 Unlike other sample sources (serum or tissue), obtaining urine is not an invasive procedure, and it can be easily collected, allowing for sequential sampling. In the case of LN, the urine is physically close to the site of activity of the disease, being an interesting sample for monitoring of patients with LN.…”

Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications

“…NS has a complex pathogenesis with multiple case types, and there are no accepted biomarkers. In this regard, numerous studies have identified urine protein biomarkers, which show promise in the diagnosis of NS, including vitamin D binding protein, neutrophil gelatinase-associated lipocalin, CD80, , but most of these studies were conducted in children and did not yield consistent results. There is a lack of systematic research on searching for biomarkers in blood system, and the assay based on circulating markers may detect NS at early stage, particularly in conjunction with urine-based biomarker test.…”

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology

“…T he increasing burden of chronic diseases indicates the need for noninvasive, easily accessible, stable, and cost-effective biomarkers. The field of urinary proteomics/peptidomics has developed extensively and consistently over the past two decades, with a focus on kidney and cardiovascular diseases [1][2][3][4][5][6]. Thousands of proteins present in the human body are ultimately degraded by ubiquitous proteolytic enzymes, resulting in the generation of protein fragments, that is, peptides.…”