Abstract

In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a “liquid biopsy” to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.

Highlights

  • Kidney diseases can be caused by a variety of insults such as hypertension, genetic or metabolic disorders, infections, toxins, ischemia, immunological disorders or allograft rejection

  • Siwy et al [41] found that, while no differences in estimate of the glomerular filtration rate (eGFR) were observed in the overall cohort of patients treated with linagliptin as compared to placebo, use of CKD273 classification allowed the stratification of patients into high-risk and low-risk of progression

  • 29 peptides were found in common with the CKD273 classifier, which as expected poorly identified patients with improved eGFR [45]. These results suggest that chronic kidney disease (CKD) patients with improving renal function undergo different biological and/or molecular processes compared to CKD progressors, which may lead to the identification of new molecular targets for CKD remission [45]

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Summary

Introduction

Kidney diseases can be caused by a variety of insults such as hypertension, genetic or metabolic disorders, infections, toxins, ischemia, immunological disorders or allograft rejection. Urinary proteomics has been applied extensively these last several years, with a view to identifying markers of kidney disease progression, diagnosis, or responsiveness to therapy [2,4,6,7,8] Both proteins and peptides (short aminoacid chains) are contained in urine but peptides are mainly the results of complex molecular post-translational modifications of larger polypeptide molecules. Endogenous urinary peptides are favored over urinary full-length proteins as noninvasive biomarkers of kidney disease, for several reasons [5] These include: the fact that, being filtered by the kidney and excreted under physiological conditions, urinary peptide can show changes in content before failure of the glomerular filtration barrier (in contrast to proteins); the higher stability of the urinary peptidome, which is less amenable to damage in the bladder than the urinary proteome; and the possibility of direct mass spectrometry analysis without the tryptic digestion that is required for urinary protein before analysis and that introduces additional variability [5]. After a brief section on available technologies, we review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases, covering the publication years 2005–2019

Techniques for Urinary Peptidome Analysis
Chronic Kidney Disease
Acute Kidney Injury
Kidney Transplantation
Glomerulonephritis
Findings
Conclusions
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