Urine peptides enable non-invasive differential diagnosis of nodular diabetic nephropathy
Kondyli M, Siwy J, Jaimes Campos MA, Amann KU, Beige J, Keller F, Mischak H, Frantzi M, Wendt R, Rossing P, Rupprecht H, Catanese L, Jankowski V (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 238
Article Number: 113396
DOI: 10.1016/j.diabres.2026.113396
Abstract
Aims: Risk stratification in diabetic kidney disease is challenging. Identifying nodular diabetic nephropathy (NDN), the most specific histological feature of diabetic nephropathy (DN), associated with poor prognosis, currently requires kidney biopsy. We aimed to identify urinary peptide biomarkers distinguishing NDN from other chronic kidney disease etiologies in diabetes (nNDN). Methods: In this case-control study, urinary peptide profiles from biopsy-proven DN patients (43 NDN, 38 nNDN) were analyzed using capillary electrophoresis-mass spectrometry. Real patient data were combined with synthetic datasets generated using a Gaussian copula approach and divided into discovery and validation cohorts. Differential peptides were identified by Wilcoxon testing with Benjamini-Hochberg correction, and combined into a support vector machine model. Results: In the discovery cohort, 207 peptides were significantly altered. NDN was characterized by reduced collagen fragments and increased fibrinogen, apolipoprotein A-IV, and α1-antitrypsin peptides. The 99-peptide classifier (NDN99) discriminated NDN from nNDN with an AUC of 0.87 (combined validation) and 0.79 (real-patient validation). NDN99 predicted major adverse kidney events (MAKE; death, kidney failure, or 40% eGFR loss), and outperformed histology (HR = 2.9, p = 0.0006 vs HR = 1.9, p = 0.04). Conclusions: Urinary peptide signatures enable non-invasive discrimination of NDN and predict MAKE, potentially complementing kidney biopsy for subtype identification and risk stratification in DN.
Authors with CRIS profile
Involved external institutions
mosaiques diagnostics and therapeutics AG
Germany (DE)
Klinikum St. Georg
Germany (DE)
Medizinische Universität Innsbruck
Austria (AT)
Steno Diabetes Center
Denmark (DK)
Klinikum Bayreuth
Germany (DE)
Universitätsklinikum Aachen (UKA)
Germany (DE)
Germany (DE)
Klinikum St. Georg
Germany (DE)
Medizinische Universität Innsbruck
Austria (AT)
Steno Diabetes Center
Denmark (DK)
Klinikum Bayreuth
Germany (DE)
Universitätsklinikum Aachen (UKA)
Germany (DE)
How to cite
APA:
Kondyli, M., Siwy, J., Jaimes Campos, M.A., Amann, K.U., Beige, J., Keller, F.,... Jankowski, V. (2026). Urine peptides enable non-invasive differential diagnosis of nodular diabetic nephropathy. Diabetes Research and Clinical Practice, 238. https://doi.org/10.1016/j.diabres.2026.113396
MLA:
Kondyli, Margarita, et al. "Urine peptides enable non-invasive differential diagnosis of nodular diabetic nephropathy." Diabetes Research and Clinical Practice 238 (2026).
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