Urinary proteomics for the study of genetic kidney diseases

ABSTRACT

Despite their low prevalence, genetic kidney diseases (GKD) still represent a serious health problem. They often lead to kidney failure and to the consequent need of dialysis or kidney transplant. To date, reliable diagnosis requires laborious genetic tests and/or a renal biopsy. Moreover, only scant and non-specific markers exist for prognostic purposes. Biomarkers assayed in an easily available and low-cost sample, such as urine, would be highly valuable. Urinary proteomics can provide clues related to their development through the identification of differentially expressed proteins codified by the affected genes, or other dis-regulated species, in total or fractionated urine, providing novel mechanistic insights. In this review, the authors summarize and discuss the results of the main proteomic investigations on GKD urine samples and in urinary extracellular vesicles.

KEYWORDS:

• urine
• extracellular vesicles
• biomarkers
• exosomes
• kidney
• genetic diseases

Acknowledgements

The authors wish to thank Dr. Andrew Smith for English revision.

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Most genetic kidney diseases are very rare and neglected pathologies, but as a whole, they represent a significant burden on the health-care systems.

• Their diagnosis relies on expensive and laborious genetic tests and/or tissue biopsy.

• Robust biochemical markers and prognostic elements are lacking.

• Proteomic studies performed on urine, a cheap and highly accessible sample, in direct contact with defective cells, are providing new indicators of disease presence and progression.

• The small case records available for most genetic kidney diseases (GKDs) dictate the preference for highly standardized studies performed by robust and possibly integrated proteomic technologies.

• Both total and fractionated urine (urinary extracellular vesicles) are potential sources of differential proteins.

• Research should focus on the soundest differential proteins, demonstrating their specificity and explaining their qualitative and quantitative correlation with the primary genetic defect.

• The knowledge of the full differential urinary proteome in each GKD can also provide clues related to the understanding of their pathophysiology and potentially facilitate major improvements of the current state of the art.