Differentiating primary and secondary FSGS using non-invasive urine biomarkers.
Catanese L, Siwy J, Wendt R, Amann KU, Beige J, Hendry B, Mischak H, Mullen W, Paterson I, Schiffer M, Wolf M, Rupprecht H (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 17
Journal Issue: 2
DOI: 10.1093/ckj/sfad296
Abstract
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is divided into genetic, primary (p), uncertain cause, and secondary (s) forms. The subclasses differ in management and prognosis with differentiation often being challenging. We aimed to identify specific urine proteins/peptides discriminating between clinical and biopsy-proven pFSGS and sFSGS. METHODS: Sixty-three urine samples were collected in two different centers (19 pFSGS and 44 sFSGS) prior to biopsy. Samples were analysed using capillary electrophoresis-coupled mass spectrometry. For biomarker definition, datasets of age-/sex-matched normal controls (NC, n = 98) and patients with other chronic kidney diseases (CKDs, n = 100) were extracted from the urinary proteome database. Independent specificity assessment was performed in additional data of NC (n = 110) and CKD (n = 170). RESULTS: Proteomics data from patients with pFSGS were first compared to NC (n = 98). This resulted in 1179 biomarker (P < 0.05) candidates. Then, the pFSGS group was compared to sFSGS, and in a third step, pFSGS data were compared to data from different CKD etiologies (n = 100). Finally, 93 biomarkers were identified and combined in a classifier, pFSGS93. Total cross-validation of this classifier resulted in an area under the receiving operating curve of 0.95. The specificity investigated in an independent set of NC and CKD of other etiologies was 99.1% for NC and 94.7% for CKD, respectively. The defined biomarkers are largely fragments of different collagens (49%). CONCLUSION: A urine peptide-based classifier that selectively detects pFSGS could be developed. Specificity of 95%-99% could be assessed in independent samples. Sensitivity must be confirmed in independent cohorts before routine clinical application.
Authors with CRIS profile
Involved external institutions
Klinikum Bayreuth
Germany (DE)
mosaiques diagnostics and therapeutics AG
Germany (DE)
Klinikum St. Georg
Germany (DE)
KfH Kuratorium für Dialyse und Nierentransplantation e.V.
Germany (DE)
Travere Therapeutics, Inc.
United States (USA) (US)
University of Glasgow
United Kingdom (GB)
Germany (DE)
mosaiques diagnostics and therapeutics AG
Germany (DE)
Klinikum St. Georg
Germany (DE)
KfH Kuratorium für Dialyse und Nierentransplantation e.V.
Germany (DE)
Travere Therapeutics, Inc.
United States (USA) (US)
University of Glasgow
United Kingdom (GB)
How to cite
APA:
Catanese, L., Siwy, J., Wendt, R., Amann, K.U., Beige, J., Hendry, B.,... Rupprecht, H. (2024). Differentiating primary and secondary FSGS using non-invasive urine biomarkers. Clinical Kidney Journal, 17(2). https://doi.org/10.1093/ckj/sfad296
MLA:
Catanese, Lorenzo, et al. "Differentiating primary and secondary FSGS using non-invasive urine biomarkers." Clinical Kidney Journal 17.2 (2024).
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