Perioperative Role Of Vascular Endothelial Growth Factor In Cardiac Surgery-associated Acute Kidney Injury (PROVE-AKI)

The goal of this prospective observational study is to find out whether the protein vascular endothelial growth factor (VEGF) measured in blood and urine can predict which patients will develop acute kidney injury (AKI) after heart-type surgery that uses a heart-lung machine (cardiopulmonary bypass).

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Kidney Injury; Cardiac Surgery Associated - Acute Kidney Injury

Detailed Description

Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a common and serious complication affecting 20-30% of patients undergoing cardiac surgery, with significant implications for short- and long-term morbidity and mortality. The pathophysiology of CSA-AKI is multifactorial and incompletely understood. It involves hypoperfusion, ischemia-reperfusion injury, inflammation, and oxidative stress. Emerging evidence suggests that vascular endothelial dysfunction and microvascular injury play central roles in the development and progression of CSA-AKI. Vascular endothelial growth factor (VEGF) is a key regulator of endothelial cell survival, vascular permeability, inflammation, and angiogenesis. VEGF appears to play a critical role in maintaining renal microvascular homeostasis. While renal VEGF expression in vitro is induced by hypoxia, its renal expression and protein plasma levels have been shown to drop significantly following ischemia-reperfusion injury in a mouse model. These observations have been supported by an observational study that found an approximately 2-fold decrease in plasma concentrations of VEGF by 6 hours in patients that had underwent cardiac surgery with cardiopulmonary bypass (CPB). Conversely, higher early postoperative VEGF plasma concentrations have been independently associated with significantly reduced risk of AKI, shorter AKI duration and improved survival, suggesting a protective role for VEGF in the acute phase of CSA-AKI. However, while VEGF appears to be nephroprotective in the acute phase after cardiac surgery, it potentially contributes to chronic kidney disease (CKD) progression due to fibrosis and is associated with higher risk for progression to end stage kidney disease in patients with diabetic nephropathy. Despite these insights, the reliance of the only clinical study by Mansour et al. on plasma VEGF measurements may limit the precision with which renal VEGF dynamics can be characterized. Plasma VEGF reflects contributions from multiple non-renal sources, including platelets, leukocytes, vascular endothelium, and other tissues, all of which are substantially perturbed in the context of cardiac surgery. The resulting hemodilution, platelet activation and systemic inflammatory response inherent to extracorporeal circulation represent important confounders of circulating VEGF levels that are unrelated to renal pathophysiology. Consequently, the observed 2-fold decrease in plasma VEGF following cardiac surgery³ likely represents an attenuated and partially masked signal of what preclinical data suggest to be a far more pronounced local renal VEGF suppression. In contrast, urinary VEGF may provide a more specific representation of intrarenal VEGF (predominantly produced by glomerular podocytes) that is less susceptible to systemic confounders. Given the magnitude of renal VEGF suppression documented in the IRI model, urinary VEGF concentrations would be expected to demonstrate a substantially larger and more consistent signal in patients developing CSA-AKI compared to plasma-based measurements. The precise role of VEGF in the pathophysiology of CSA-AKI thus remains unclear. To date, urinary VEGF has not been systematically evaluated as a biomarker in the context of CSA-AKI, and direct comparative data with plasma VEGF in this setting are lacking. The temporal changes of VEGF expression, its relationship to specific injury mechanisms such as ischemia-reperfusion injury, oxidative stress, and inflammation and its potential utility as a predictive biomarker in the plasma/urine or therapeutic target require further investigation. The objective of this study is to comprehensively evaluate the role of VEGF in CSA-AKI by examining its urine and plasma concentration over time in relation to clinical outcomes. First, we aim to determine whether perioperative VEGF levels can serve as a predictive biomarker for CSA- AKI development, severity, and duration. Second, we aim to elucidate the mechanistic pathways through which VEGF influences AKI and recovery in the cardiac surgery setting. Understanding the significance of VEGF in CSA-AKI may identify novel opportunities for risk stratification and possibly therapeutic interventions to improve kidney outcomes in this high-risk patient population.

• Study Type: Observational
• Enrollment (Estimated): 220

Contacts and Locations

• Study Contact: Name: Alexander Zarbock, MD; Phone Number: +49251-8347255; Email: zarbock@uni-muenster.de
• Study Contact Backup: Name: Moritz Mertes, MD; Phone Number: +49251-8347283; Email: moritz.mertes@ukmuenster.de

Study Locations

• Germany
  • Münster, Germany, 48149
    • University Muenster, University Hospital Muenster, Department of Anesthesiology, Intensive Care and Pain Medicineperative
    • Contact: Alexander Zarbock, MD; Phone Number: +49251-8347255; Email: zarbock@uni-muenster.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing elective cardiac surgery with use of cardiopulmonary bypass

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Elective cardiac surgery using cardiopulmonary bypass
3. Written informed consent

Exclusion Criteria:

1. Pre-existing chronic kidney disease with an eGFR <20 ml/min/1,73m2
2. Usage of VEGF-inhibitors
3. Patients with pre-existing AKI within the last 30 days

4. Patients undergoing one of the following surgeries:

   1. Emergency surgery
   2. LVAD-implantation
5. Patients after cardiac arrest requiring cardiopulmonary resuscitation within the last 6 months
6. Patients on vasopressors, inotropes or mechanical circulatory support before surgery

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Elective cardiac surgical patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Association of vascular endothelial growth factor (VEGF) levels with postoperative acute kidney injury	From baseline to postoperative day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in VEGF levels between patients with and without chronic kidney disease		From Baseline to postoperative day 3
Difference in VEGF levels between patients with transient and persistent acute kidney injury (AKI) after cardiac surgery	Comparison of VEGF levels between patients with transient AKI (resolving within 48 hours of onset) and persistent AKI (lasting more than 48 hours), among patients who develop AKI within the first 3 postoperative days following cardiac surgery.	Up to 30 days postoperatively
Association of VEGF levels with length of ICU-stay	Association between perioperative VEGF levels and the duration of index intensive care unit (ICU) stay following cardiac surgery.	Up to 30 days postoperatively
Association of VEGF levels with length of hospital stay	Association between perioperative VEGF levels and the duration of index hospital stay following cardiac surgery.	Up to 30 days postoperatively
Association of VEGF levels with 30-day all-cause mortality		From enrolment to postoperative day 30
Association of VEGF levels with Major Adverse Kidney Events up to day 30 (MAKE30)		From enrolment to postoperative day 30
Association of VEGF plasma to urine ratio with postoperative AKI		From Baseline to postoperative day 3

Collaborators and Investigators

• Sponsor: Universität Münster

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: August 27, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: vascular endothelial growth factor; vegf
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: AnIt26-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this study, after deidentification (text, tables, figures, and appendices)
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication

IPD Sharing Access Criteria

With whom? Researchers who provide a methodologically sound proposal

By what mechanism will data be made available? Proposals should be directed to zarbock@uni-muenster.de. To gain access, data requestors will need to sign a data access agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No