Proteomic biomarkers in kidney disease: issues in development and implementation

Abstract

Proteomic biomarkers offer the hope of improving the management of patients with kidney diseases by enabling more accurate and earlier detection of renal pathology than is possible with currently available biomarkers, serum creatinine and urinary albumin. In addition, proteomic biomarkers could also be useful to define the most suitable therapeutic targets in a given patient or disease setting. This Review describes the current status of proteomic and protein biomarkers in the context of kidney diseases. The valuable lessons learned from early clinical studies of potential proteomic biomarkers in kidney disease are presented to give context to the newly identified biomarkers, which have potential for actual clinical implementation. This article also includes an overview of protein-based biomarker candidates that are undergoing development for use in nephrology, focusing on those with the greatest potential for clinical implementation. Relevant issues and problems associated with the discovery, validation and clinical application of proteomic biomarkers are discussed, along with suggestions for solutions that might help to guide the design of future proteomic studies. These improvements might remove some of the current obstacles to the utilization of proteomic biomarkers, with potentially beneficial results.

Urinary peptidomics provides a noninvasive humanized readout of diabetic nephropathy in mice

“…We and others have shown that urine is a rich and non-invasive source of biomarkers of disease in humans [17][18][19] . Mass spectrometry-based analysis of the endogenous urinary peptidome (i.e., 5 not generated by trypsin digestion) allows the assessment of thousands of urinary peptides at once.…”

“…Mass spectrometry-based analysis of the endogenous urinary peptidome (i.e., 5 not generated by trypsin digestion) allows the assessment of thousands of urinary peptides at once. Combined in multi-molecular classifiers of tens to hundreds of peptides, these urinary peptides have proven their ability to faithfully describe complex diseases including kidney disease 17,20 , cardiovascular disease 21 , graft-versus-host disease 22 , and cholangiocarcinoma 23 .…”

Urinary Protein Biomarkers in Chronic Kidney Disease

“…Those are the main reasons why the urine is widely used for proteomic biomarkers discovery [17,23,24]. Single-protein biomarkers are not effective and suitable to reflect complex diseases, such as CKD and therefore combination and simultaneous use of multiple biomarkers should improve the diagnostic performance [4,17,25]. Combination of multiple biomarkers in high-dimensional classifiers, substantially outperform linear combination of biomarkers [26].…”

“…Currently used diagnostic and staging tools are mostly based on non-invasive analysis of serum creatinine and/ or urinary albumin and estimation of glomerular filtration rate (eGFR). These biomarkers although widely accepted, frequently fail to identify patients at higher risk of progression or death [3,4]. They are also not reliable parameters for early diagnosis, as rising of serum creatinine levels above normal is only evident after substantial loss of renal function and its level may be affected by additional factors, such as the loss of muscle mass [5].…”

“…Additionally, there is a lack of understanding why some of the CKD patients progress to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT), while others die prematurely due to cardiovascular diseases (CVD) instead of progressing to ESRD [3,[14][15][16][17]. Ultimately, it is important to identify additional noninvasive diagnostic biomarkers for early detection of renal diseases and possible timely therapeutical interventions and prognostics biomarkers as reliable predictors of progression towards ESRD and/or death outcomes [3,4,11,[18][19][20].…”