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Association of Urinary Complement Peptides with Kidney Function and Progression of Kidney Disease.

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Title: Association of Urinary Complement Peptides with Kidney Function and Progression of Kidney Disease.
Authors: Nguyen, Thi Minh Nghia, Kondyli, Margarita, Mischak, Harald, Keller, Felix, Beige, Joachim, Latosinska, Agnieszka, Siwy, Justyna
Source: International Journal of Molecular Sciences; Feb2026, Vol. 27 Issue 4, p1982, 16p
Subject Terms: COMPLEMENT (Immunology), DISEASE progression, PROGNOSTIC models, CHRONIC kidney failure, KIDNEY physiology, GLOMERULAR filtration rate
Abstract: Complement activation has been implicated in many kidney diseases, but it remains unclear whether urinary complement-derived peptides reflect kidney function beyond albuminuria and predict disease progression. We analyzed mass spectrometry-based urinary peptidomics data from 10,939 individuals with chronic kidney disease and healthy controls. Fifty-eight complement-derived peptides were identified, predominantly from complement factor B (CFB) and C3. Of these, fifty-two were significantly related to estimated glomerular filtration rate (eGFR) independently of albuminuria, mostly inversely. Several C3- and CFB-derived peptides were also associated with specific kidney disease etiologies. In a longitudinal analysis of 3964 individuals (median follow-up 2.91 years), 18 of these peptides were significantly related to a major adverse kidney event (MAKE, defined as ≥40% eGFR decline, end-stage kidney disease or death) after adjustment for clinical covariates, indicating prognostic information beyond traditional risk markers. In the independent test cohort, combining these peptides in a machine learning-based model and adding the resulting risk score to clinical parameters significantly improved MAKE prediction (AUC 0.801 vs. 0.778, p = 0.031). Thus, urinary complement-derived peptides provide independent and clinically relevant information on kidney function and disease progression, supporting their potential value in the identification of high-risk patients and guiding more personalized therapy. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
Description
Abstract:Complement activation has been implicated in many kidney diseases, but it remains unclear whether urinary complement-derived peptides reflect kidney function beyond albuminuria and predict disease progression. We analyzed mass spectrometry-based urinary peptidomics data from 10,939 individuals with chronic kidney disease and healthy controls. Fifty-eight complement-derived peptides were identified, predominantly from complement factor B (CFB) and C3. Of these, fifty-two were significantly related to estimated glomerular filtration rate (eGFR) independently of albuminuria, mostly inversely. Several C3- and CFB-derived peptides were also associated with specific kidney disease etiologies. In a longitudinal analysis of 3964 individuals (median follow-up 2.91 years), 18 of these peptides were significantly related to a major adverse kidney event (MAKE, defined as ≥40% eGFR decline, end-stage kidney disease or death) after adjustment for clinical covariates, indicating prognostic information beyond traditional risk markers. In the independent test cohort, combining these peptides in a machine learning-based model and adding the resulting risk score to clinical parameters significantly improved MAKE prediction (AUC 0.801 vs. 0.778, p = 0.031). Thus, urinary complement-derived peptides provide independent and clinically relevant information on kidney function and disease progression, supporting their potential value in the identification of high-risk patients and guiding more personalized therapy. [ABSTRACT FROM AUTHOR]
ISSN:16616596
DOI:10.3390/ijms27041982