Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications

Idiopathic nephrotic syndrome (NS) is a heterogeneous
group of
glomerular disorders which includes two major phenotypes: minimal
change disease (MCD) and focal segmental glomerulosclerosis (FSGS).
MCD and FSGS are classic types of primary podocytopathies. We aimed
to explore the molecular mechanisms in NS triggered by primary podocytopathies
and evaluate diagnostic value of the selected proteomic signatures
by analyzing blood proteome profiling. Totally, we recruited 90 participants
in two cohorts. The first cohort was analyzed using label-free quantitative
(LFQ) proteomics to discover differential expressed proteins and identify
enriched biological process in NS which were further studied in relation
to clinical markers of kidney injury. The second cohort was analyzed
using parallel reaction monitoring-based quantitative proteomics to
verify the data of LFQ proteomics and assess the diagnostic performance
of the selected proteins using receiver-operating characteristic curve
analysis. Several biological processes (such as immune response, cell
adhesion, and response to hypoxia) were found to be associated with
kidney injury during MCD and FSGS. Moreover, three proteins (CSF1,
APOC3, and LDLR) had over 90% sensitivity and specificity in detecting
adult NS triggered by primary podocytopathies. The identified biological
processes may play a crucial role in MCD and FSGS pathogenesis. The
three blood protein markers are promising for diagnosing adult NS
triggered by primary podocytopathies.