Post-Marketing Study to Assess the Safety & Efficacy of RenalGuard® Therapy for Prevention CSA-AKI (KIDNEY-II)

Post-Marketing Clinical Follow Up Study to Further Assess the Safety & Efficacy of RenalGuard® Therapy in the Prevention of Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI)

The goal of this clinical trial is to assess the effect of RenalGuard Therapy in reducing the rates of Acute Kidney Injury (AKI) within 72 hours after cardiac surgery in patients at risk of developing Cardiac Surgery Associated AKI (CSA-AKI) compared to standard-of-care (SoC).

Participants will be randomized (1:1) to one of the two study groups. The Treatment study group will be managed with the RenalGuard System. The RenalGuard treatment will start after induction of anesthesiology and will run during surgery and for 6-7 hours in the Intensive Care Unit (ICU). The treatment will aim to achieve a urine rate above a predefined urine rate threshold. Patients in the control group will be managed based on the usual clinical practice in cardiac surgery centres as detailed in the recommendations for CSA-AKI prevention by accepted clinical guidelines.

For both study groups general anaesthesia, cardiopulmonary bypass (CPB) run and overall patient care will be based on SoC for cardiac surgery.

Patients will be followed up for up to 7 days post surgery or until discharge, which ever comes first.

Long-term follow up will be performed at 90 days post surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiac Surgery Associated - Acute Kidney Injury; AKI - Acute Kidney Injury
• Intervention / Treatment: Other: Standard of Care (SOC); Device: RenalGuard Therapy

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium
    • Jessa Medica Center
• Germany
  • Munich, Germany
    • TUM Klinikum Deutsches Herzzentrum
  • Münster, Germany
    • Uniklinikum Münster
• Israel
  • Haifa, Israel
    • Rambam Medical Center
  • Petah Tikva, Israel
    • Rabin Medical Center - Belinson Campus
• Spain
  • Barcelona, Spain
    • Hospital de La Santa Creu i Sant Pau
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female and >18 years of age
2. Patient able to give written consent

3. Scheduled for the following non-emergent cardiac surgery procedure requiring CPB, isolated or in combination:

   • coronary artery bypass graft (CABG)
   • aortic valve replacement or repair alone, with or without aortic root repair
   • mitral, tricuspid, or pulmonic valve replacement or repair
   • simultaneous replacement of several cardiac valves
   • CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair
   • Surgery on the aorta: aortic root and/ or ascending aorta
   • Atrial fibrillation (AF) ablation surgery if combined with other cardiac procedures.
   • Atrial septal defect (ASD) closure if combined with other cardiac procedures.
   • Excision of myxoma if combined with other cardiac procedures

4. Have at least one of the following risk factors for CSA-AKI:

   • CKD-EPI eGFR 20-59 mL/min/1.73 m²
   • Age ≥ 75 years
   • Undergoing combined surgery (e.g. CABG + Valve)
   • Logistic EuroScore of ≥5 or, Euroscore II of ≥4 or Society of Thoracic Surgeons (STS) Score ≥4
   • Left ventricular ejection fraction (LVEF) ≤ 35% by invasive or noninvasive diagnostic cardiac imaging performed within 90 days prior to surgery.
   • Insulin-requiring diabetes
   • Non-insulin-requiring diabetes with HbA1C ≥ 6.1% in the last 6 months
   • Preoperative anemia within 4 weeks of surgery

Exclusion Criteria:

1. Patient requiring emergency surgery
2. Surgery to be performed without CPB
3. Patient receiving furosemide at a dose>100 mg/day orally (or the equivalent dose of an alternative loop diuretic) in the last week
4. Patient who cannot be urethrally catheterize for any reason
5. Patients already dialysis dependent
6. Patients with CKD-EPI eGFR <20 mL/min/1.73 m²
7. Known or suspected AKI (KDIGO criteria) at the time of screening
8. Patients participating in another interventional drug or device study or have received an investigational drug or device treatment within the last 30 days
9. Pregnant patient, self-reported
10. Patients whose planned surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature < 28°Celsius (82.4° Fahrenheit)
11. Patient with suspected or confirmed bacteraemia, endocarditis, or pyelonephritis at hospital admission
12. Patients with pneumonia, aspiration, or bilateral pulmonary infiltrates from an infectious aetiology reported on chest x-ray or CT scan in the last 7 days
13. Patients in cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices (Impella Heart Pump, IABP) within 24 hours prior to surgery
14. Patients on extracorporeal membrane oxygenation (ECMO) or durable ventricular assist device (VAD) at the time of screening, or planned use within 24h prior to surgery
15. Patients currently treated with chemotherapy or radiation therapy that may have an impact on kidney function.
16. Patient underwent prior solid organ transplantation
17. Patients underwent major surgery within the last 3 months
18. Any condition which, in the judgement of the investigator, might increase the risk to the patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Standard of care	Other: Standard of Care (SOC); Standard of care
Experimental: RenalGuard Therapy	Device: RenalGuard Therapy; RenalGuard Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSA-AKI incidence between study groups	CSA-AKI is defined as when any of the following three criteria are met: An increase in serum creatinine (SCr) by ≥0.3 mg/dl (≥26.5 umol/l) within 72 hours compared to the baseline value; OR; An increase in SCr by ≥1.5 times from SCr value at baseline within 72 hours; OR; Use of Renal Replacement Therapy (RRT) within 7 days of surgery or by hospital discharge (whichever is the earliest)	Within 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite safety endpoint which includes: Significant severe clinically meaningful change in electrolytes (K+, Mg+2, Na+), New onset of postoperative atrial fibrillation, and Pulmonary edema		Within 72 hours
CSA-AKI Stage	CSA-AKI severity by stage distribution between the study groups	Within 72 hours
CSA-AKI Incidence	AKI incidence within 7 days based on the KDIGO definition described in the primary endpoint section	Within 7 days
CSA-AKI Duration	Duration of AKI within 7 days of surgery	Within 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of Major Adverse Kidney Events (MAKE)	MAKE-90 will be defined as: Death within 90 days; Any dialysis within 90 days; A decrease of 25% in Estimate glomerular filtration rate (eGFR) from baseline eGFR level at 90 days	90 days post-surgery
ICU and in-hospital length of stay		7 days
Cumulative costs of ICU stay		7 days

Collaborators and Investigators

• Sponsor: CardioRenal Systems, Inc.
• Investigators: Principal Investigator: Jacob Raphael, MD, Thomas Jefferson University Hospitals

Publications and helpful links

General Publications

• Luckraz H, Giri R, Wrigley B, Nagarajan K, Senanayake E, Sharman E, Beare L, Nevill A. Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial. Eur J Cardiothorac Surg. 2021 Apr 13;59(3):562-569. doi: 10.1093/ejcts/ezaa395.
• Luckraz H, Giri R, Wrigley B, Nagarajan K, Senanayake E, Sharman E, Beare L, Nevill A. Balanced forced-diuresis as a renal protective approach in cardiac surgery: Secondary outcomes of electrolyte changes. J Card Surg. 2021 Nov;36(11):4125-4131. doi: 10.1111/jocs.15925. Epub 2021 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: February 1, 2025
• First Posted (Actual): February 6, 2025

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Acute Kidney Injury; AKI; CSA-AKI; RenalGuard; Cardiac Surgery Associated AKI; AKI Prevention
• 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; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: RG-CSA-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No