Abstract: FR-PO0376
Plasma-Derived Fetuin-A Repletion Attenuates Renal Ischemia-Reperfusion Injury and Maladaptive Repair
Session Information
- AKI: Mechanisms - Metabolism and Repair
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Rudloff, Stefan, Inselspital Universitatsspital Bern, Bern, BE, Switzerland
- Correia, Miguel, Universitat Bern Medizinische Fakultat, Bern, BE, Switzerland
- Jahnen-Dechent, Willi, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, NRW, Germany
- Huynh-Do, Uyen, Inselspital Universitatsspital Bern, Bern, BE, Switzerland
Background
Ischemia-reperfusion injury (IRI) drives acute kidney injury (AKI) through necrosis, inflammation, and disturbed calcium-phosphate (CaP) mineral homeostasis, creating a self-amplifying pathway that exacerbates renal injury, promotes maladaptive repair and fibrotic remodeling, and ultimately contributes to chronic kidney disease (CKD). Fetuin-A (FA) is an abundant plasma glycoprotein that neutralizes nascent CaP minerals and prevents the formation of cytotoxic calciprotein particles (CPPs). Here, we tested whether human plasma-derived fetuin-A (hpFA) supplementation can blunt renal IRI and downstream remodeling.
Methods
hpFA activity was characterized using calcification propensity assays (T50), and its pharmacokinetics were determined in mice. Endogenous FA kinetics were examined in mice subjected to unilateral renal IRI (uIRI) or sham surgery, in porcine limb IRI, and in human cohorts undergoing ischemic surgery or presenting with acute inflammatory disease. In mice, hpFA was administered prophylactically before or therapeutically after uIRI, followed by assessment of tubular injury, inflammatory activation, and fibrotic remodeling. Fluorescent FA was used as a probe to visualize CPPs in tissue sections.
Results
In mice, endogenous FA decreased within minutes after surgery and redistributed to injured tissues, including sites of surgical trauma. Fluorescent FA staining revealed increased renal CPPs after uIRI but also sham surgery, with even higher abundance in kidneys of unoperated FA-deficient mice. In uIRI, hpFA supplementation dose-dependently reduced tissue CPP burden, blunted early tubular stress and inflammatory signaling, and attenuated later fibrotic remodeling. Systemic FA levels also declined after porcine limb IRI and in human patients undergoing cardiovascular surgery. In kidney transplant recipients and patients with severe inflammatory disease, lower FA levels were associated with adverse clinical outcomes.
Conclusion
FA depletion is an immediate, conserved response to acute injury that may expose the kidney to CaP mineral-driven inflammatory cascades. Repletion with exogenous hpFA can interrupt this self-reinforcing injury response and limit maladaptive repair. These findings support FA as both a risk-stratification biomarker and a potential therapeutic candidate to prevent AKI and its transition to CKD.
Funding
- Commercial Support – CSL Behring