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

International Journal of Molecular Sciences, vol. 27, pp. 1982

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.

Authors 7

1. Thi Minh Nghia Nguyen

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

2. Margarita Kondyli Aachen Institute for Molecular Cardiovascular Research

   Universitätsklinikum Aachen · Mosaiques Diagnostics and Therapeutics (Germany) · RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

3. Harald Mischak

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

4. Felix Keller

   Innsbruck Medical University · Universität Innsbruck

   Affiliation as printed

   Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Anich St. 35, 6020 Innsbruck, Austria

5. Joachim Beige

   Klinikum St. Georg · KfH Kuratorium für Dialyse und Nierentransplantation · Martin Luther University Halle-Wittenberg

   Affiliation as printed

   Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, 06108 Halle (Saale), Germany

   Department of Nephrology, Hospital St. Georg, 04129 Leipzig, Germany

   Kuratorium for Dialysis and Transplantation (KfH), 63263 Neu-Isenburg, Germany

6. Agnieszka Latosińska corresponding

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

7. Justyna Siwy

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany