Urinary Peptidomic Biomarkers in Kidney Diseases

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.

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

“…In clinical practice, kidney damage is generally detected by changes in serum creatinine and a creatinine-based eGFR, as well as protein excretion. A significant increase in serum creatinine concentration indicates that more than 50% of the glomerular function has been lost or dysfunctional [ 60 ]. Tubular dysfunction after kidney storage and transplantation is a source of elevated urea and potassium, but it may also be influenced by both rejection episodes and toxic effects of calcineurin inhibitors [ 61 ].…”

“…Neither marker is connected with molecular pathophysiology. Rather, each represents a consequence of substantial damage to the kidney, so there is a need for newer biomarkers, using proteomics or metabolomics, that enable an ability in the prediction of disease progression and the determination of therapeutic efficacy [ 60 ].…”

Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations

“…In current times, biomarkers of kidney damage, such as changes in serum creatinine and eGFR and/or urinary albumin/protein excretion, apply to a later stage of kidney injury after substantial kidney injury has occurred. Thus, there is the unmet need for new biomarkers enabling the timely and more accurate detection of kidney dysfunction, which may lead to an improvement in both short- and long-term outcomes [ 89 ]. Several cell-based and biomarker-based assays for predicting nephrotoxicity have been developed, and work is underway to examine whether these biomarkers prove useful in clinical drug trials and can be translated to clinical practice [ 82 ].…”

“…Several cell-based and biomarker-based assays for predicting nephrotoxicity have been developed, and work is underway to examine whether these biomarkers prove useful in clinical drug trials and can be translated to clinical practice [ 82 ]. Moreover, the analysis of urine peptide content (urinary peptidomics) may bring a significant improvement in the management of kidney diseases by supporting earlier and more accurate detection, prognostic assessment, and the prediction of treatment response [ 89 ]. Recent technical advances as well as certain current and projected ventures hold the promise of clinching the use of urinary peptidomics in the near future as a major part of kidney disease management.…”

Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease

“…[2] In part also due to the fact that urine albumin-to-creatinine ratio (ACR) is a clinically used biomarker of cardiovascular and kidney disease risk, [3] a substantial number of studies describe the investigation of peptides in urine (reviewed in ref. [4][5][6][7]). The special attention to investigate urinary peptides in these areas emerged from their origin.…”