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Proteinuria in urine cup

Differentiating Primary and Secondary FSGS Using Non‑Invasive Urine Biomarkers

Journal article
Published on December 4, 2023

Topics: Nephrology FSGS Review Publication Summary

Contributors:
Catanese L, Siwy J, Wendt R et al.
Name of Journal:
Clinical Kidney Journal


View Publication
DOI:
10.1093/ckj/sfad296
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Home » Publications » FSGS Urine Biomarkers

Summary

Urinary biomarkers may help distinguish between primary and secondary focal segmental glomerulosclerosis (FSGS)1


Background

Primary and secondary focal segmental glomerulosclerosis (FSGS) are podocytopathies characterized by a histologic lesion of the glomeruli that lead to proteinuria and accounts for a significant proportion of nephrotic syndrome in both adults and children.1,2,3 Both forms of FSGS differ in pathogenesis, clinical presentation, response to therapy, and recurrence risk post-transplant, making accurate diagnosis essential.1,4,5


Aim

This aim of this study was to identify a non-invasive FSGS urinary biomarker classifier capable of distinguishing primary FSGS (pFSGS) from secondary FSGS (sFSGS).1


Approach

Urine samples from 63 patients were collected from biopsy-proven FSGS patients (pFSGS, n=19; sFSGS, n=44) and analyzed using capillary electrophoresis-coupled mass spectrometry.1

For biomarker definition, datasets from age- and sex-matched normal controls (NC) and patients with other chronic kidney disease (CKD) etiologies were retrieved from a urinary proteome database.1


Findings

Potential biomarker identification

Initially, 1,179 potential candidates were identified and then narrowed to 93 through a series of analyses, forming the classifier ‘pFSGS93’.1

Performance of pFSGS93

The final classifier, pFSGS93, showed1:

  • An area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 (95% CI 0.88–1.00) in the training cohort
  • A sensitivity of 84.2% and a specificity of 100% in internal validation
  • A specificity of 95-99% in external validation against NC subjects and patients with other CKD etiologies

Biological relevance of the findings

The most significant peptides in the comparison of pFSGS versus sFSGS included upregulated collagen fragments, alpha-1-antitrypsin, E3 ubiquitin-protein ligase RNF146, complement C3, and plasminogen and decreased polymeric immunoglobulin receptor (PIGR).1

Clinical relevance of the findings

pFSGS93 could differentiate pFSGS from sFSGS in cases where biopsy or clinical data are inconclusive, or where biopsy is contraindicated, with 84% sensitivity and 100% specificity.1


Key takeaway

The urinary peptide classifier pFSGS93 offers a promising non-invasive method to distinguish between primary and secondary FSGS with high specificity.1 It could support diagnostic and therapeutic decisions, particularly in ambiguous clinical scenarios.1

Footnotes

This study was partially funded by Travere Therapeutics, Inc. Please see the publication for the full list of disclosures.

AUC, area under the receiver operating characteristic curve; CKD, chronic kidney disease; FSGS, focal segmental glomerulosclerosis; NC, normal controls, pFSGS, primary FSGS; sFSGS, secondary FSGS; PIGR, polymeric immunoglobulin receptor; ROC, receiver operating characteristic.

  1. Catanese L et al. Clin Kidney J. 2024;17(2):sfad296.
  2. Rosenberg AZ, Kopp JB. Clin J Am Soc Nephrol. 2017;12:502–517.
  3. McGrogan A et al. Nephrol Dial Transplant. 2011;26(2):414–430
  4. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100(4S):S1–S276.
  5. Uffing A et al. Clin J Am Soc Nephrol. 2020;15:247–256.

MA-DS-25-0060 | July 2025