Efficacy of perioperative recombinant human brain natriuretic peptide for preventing acute kidney injury after cardiac surgery: Rationale, design, and study protocol for a multicenter, double-blind, randomized controlled trial (PROTECT-CS).

BACKGROUND: Acute kidney injury (AKI) is one of the most common and consequential complications after cardiac surgery. Despite improvements in perioperative care, no pharmacological intervention has been definitively shown to prevent AKI following cardiac surgery. Recombinant human brain natriuretic peptide (rhBNP) shares structural and biological activity with endogenous brain natriuretic peptide and has demonstrated favorable natriuretic, diuretic, and renal hemodynamic effects in prior studies. However, robust randomized evidence on whether perioperative rhBNP can prevent AKI is lacking. DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group trial comparing perioperative rhBNP with placebo in high-risk patients undergoing elective on-pump cardiac surgery. A total of 694 participants will be randomized 1:1 to receive a continuous intravenous infusion of rhBNP (0.01 µg/kg/min) or matched normal-saline placebo, initiated between anesthesia induction and the onset of cardiopulmonary bypass and continued for 48 ± 2 hours. The primary efficacy endpoint is the incidence of AKI within 7 postoperative days defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints include AKI severity and duration, renal replacement therapy during the index hospitalization, major adverse kidney events at 30 and 90 days (MAKE-30, MAKE-90), 30-day all-cause mortality, intensive care unit and total length of stay. CONCLUSIONS: To our knowledge, PROTECT-CS is the first adequately powered, multicenter, double-blind randomized trial designed to evaluate whether perioperative rhBNP prevents AKI after high-risk cardiac surgery. The study is intended to provide high-quality evidence to inform clinical practice and future guideline recommendations on pharmacological renal protection in cardiac surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT07617675.