The Spectrum of Minimal Change Disease/Focal Segmental Glomerulosclerosis: From Pathogenesis to Proteomic Biomarker...

Area of Science:

• Nephrology
• Proteomics
• Biomarker Discovery

Background:

• Podocyte injury is central to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), with diverse, overlapping, and poorly understood pathogenic mechanisms.
• Current kidney biopsy methods do not fully capture these underlying pathologies, leading to variable treatment responses.
• Personalized management strategies are needed, guided by specific pathogenic pathways.

Purpose of the Study:

• To review the main mechanisms of podocyte injury in podocytopathies.
• To critically evaluate recent proteomic biomarker studies in the context of podocytopathies.
• To propose a sequential approach for developing diagnostic and prognostic biomarkers.

Main Methods:

• Comprehensive review of literature on podocyte injury mechanisms.
• Systematic review of proteomic studies investigating biomarkers in biofluids and kidney tissue for podocytopathies.
• Proposal of a sequential biomarker development strategy integrating tissue and biofluid proteomics.

Main Results:

• Most existing proteomic studies for podocytopathies have focused on biofluids (urine, plasma).
• Tissue proteomic studies in podocytopathies remain limited but are crucial for initial discovery.
• A gap exists in linking specific pathogenic pathways to non-invasive biomarkers.

Conclusions:

• Proteomics offers a valuable tool to elucidate podocyte injury mechanisms and identify novel biomarkers.
• A sequential approach, starting with tissue proteomics to identify candidate proteins, followed by biofluid validation, is proposed.
• This strategy could lead to a more accurate, biomarker-based diagnostic and prognostic approach for FSGS and MCD.