Soluble urokinase receptor is a kidney-specific vasoconstrictor.

Summary

Integrating a matched cardiac surgery cohort with porcine perfusion and intravital mouse imaging, the authors show that suPAR acts as a kidney-specific vasoconstrictor that reduces renal blood flow and glomerular perfusion. This mechanistic link between innate immune activation and renal hemodynamics provides a plausible causal pathway for perioperative AKI risk.

Key Findings

• Higher suPAR levels were inversely associated with baseline eGFR in a propensity-score–matched cardiac surgery cohort.
• Ex vivo porcine kidney perfusion with suPAR reduced renal blood flow and increased renal vascular resistance.
• Intravital multiphoton imaging showed suPAR-induced afferent arteriolar constriction and reduced glomerular perfusion.
• suPAR is characterized as a predominantly kidney-specific vasoconstrictor with implications for perioperative AKI.

Clinical Implications

Preoperative suPAR measurement may refine AKI risk prediction in cardiac and high-risk surgery; strategies to lower suPAR or blunt its vasoconstrictive signaling could prevent AKI. Anesthesiologists should consider suPAR when evaluating renal hemodynamic vulnerability.

Limitations

• Exact clinical sample size and interventional suPAR-lowering trials are not reported.
• Generalizability beyond cardiac surgery and species translation requires further validation.

Future Directions

Test suPAR-guided perioperative pathways and evaluate therapies that reduce suPAR levels or block downstream vasoconstrictive signaling to prevent AKI.