IV Amino Acids Enter Pediatric Heart Surgery as a Kidney-Protective Strategy
A new phase 2 trial will test whether amino acid infusion can blunt acute kidney injury after high-risk pediatric cardiac surgery. The study, known as PROTEIN, is built around a straightforward but clinically important idea: the kidneys of children undergoing cardiopulmonary bypass may be vulnerable to ischemia, inflammatory stress, and perioperative hemodynamic instability, and amino acids may help preserve renal perfusion during that insult.
The trial is designed for children with congenital heart disease who require surgery with a heart-lung bypass machine. Those operations include higher-risk procedures such as STAT mortality category 3 or greater operations, single-ventricle palliation, and tetralogy of Fallot repair. In that setting, AKI is more than a laboratory abnormality. It can extend hospitalization, complicate postoperative recovery, and increase concern for later kidney disease in a child who may need multiple operations over a lifetime.
A single sentence captures the premise of the protocol: there is no proven therapy to prevent postoperative AKI in this population.
Why Renal Perfusion Has Become the Target
The biologic rationale is tied to renal blood flow and oxygen delivery. Amino acids can increase glomerular filtration and renal oxygen consumption, a response that may paradoxically improve kidney perfusion when delivered in a controlled perioperative setting. Investigators are testing whether that physiologic effect translates into less persistent kidney injury after bypass, where tubular stress often appears early and may continue for days after surgery.
Adult cardiac surgery studies have suggested benefit, but pediatric kidneys are not simply small adult kidneys. Infants and children face different congenital lesions, different surgical exposures, and a more prolonged lifetime risk of repeated renal insults. The PROTEIN trial is intended to determine whether the same physiologic strategy can move from adult plausibility to pediatric relevance.
The Trial Design Centers on Early Kidney Injury
The study will enroll about 270 participants younger than 18 years at three hospitals: Cincinnati Children’s Hospital Medical Center, UPMC Children’s Hospital of Pittsburgh, and Nationwide Children’s Hospital. Participants will be randomized to receive either TrophAmine, the amino acid solution, or Lactated Ringer’s as a volume-matched placebo comparator. Neither families nor the medical team will know which infusion a child receives, preserving a quadruple-masked design that includes participant, care provider, investigator, and outcome assessor masking.
The amino acid arm will receive 2 grams per kilogram per day, with a maximum of 100 grams per day, for up to 72 hours. Infusion begins in the operating room and continues through the immediate postoperative period. That timing is deliberate. Kidney injury after cardiopulmonary bypass often begins before the child has left the operating room and can evolve rapidly in the first postoperative days, when serum creatinine and urinary biomarkers may change before recovery or deterioration becomes obvious at the bedside.
Biomarkers Will Track Tubular Stress Before Creatinine Catches Up
The primary outcome is persistent acute kidney injury, defined by KDIGO serum creatinine criteria lasting more than 48 hours after cardiopulmonary bypass exposure. Persistence matters because a transient creatinine bump and a sustained renal insult do not carry the same physiologic meaning. A child whose kidney injury clears quickly may have experienced reversible stress, while prolonged elevation implies a more durable tubular and hemodynamic problem.
Urine biomarker measurement adds a second layer of renal surveillance. The trial will evaluate NGAL, KIM-1, and L-FABP as markers of tubular injury, with sampling before surgery, 6 to 12 hours after bypass, and on postoperative days 1 and 2. Those markers are biologically attractive because they can rise before creatinine fully reflects nephron injury. In practical terms, they may reveal whether the amino acid infusion alters the early molecular footprint of kidney damage even if serum creatinine moves more slowly.
The biomarker strategy also speaks to a common problem in pediatric AKI research: creatinine is an imperfect signal in children, especially after major surgery when fluid shifts, muscle mass, and changing volume status complicate interpretation. By pairing serum criteria with urinary injury markers, the trial is attempting to capture both the clinical syndrome and the renal tissue response behind it.
Secondary Endpoints Extend Beyond the Kidney
Beyond the primary renal endpoint, the study will assess dichotomous AKI using KDIGO criteria during the first seven postoperative days. It will also track MAKE-90, ventilator-free days at 28 days, and days alive and out of the hospital at 90 days. Those outcomes are clinically meaningful because kidney injury after cardiac surgery rarely occurs in isolation. It can prolong mechanical ventilation, slow extubation, complicate fluid management, and delay discharge.
A favorable kidney signal would need to translate into bedside gains to matter in practice. Fewer ventilator days and more days alive outside the hospital would suggest that a renal intervention may be influencing recovery in a broader sense, not just shifting a laboratory value.
Eligibility Reflects a High-Risk but Carefully Selected Cohort
The eligibility criteria narrow the study to children most likely to experience renal stress while excluding conditions that could confound the intervention. Children with known or suspected inborn errors of metabolism, weight under 5 kg, chronic kidney disease with estimated GFR below 60 mL/min/1.73 m², preoperative AKI, anuria at randomization, or recent parenteral nutrition are excluded. The protocol also excludes neonates under 28 days receiving ceftriaxone, preterm infants under 6 months of age born before 36 weeks’ gestation, and children receiving dialysis or preoperative extracorporeal support.
Those exclusions are clinically sensible. Amino acid metabolism, baseline kidney dysfunction, and concurrent nutritional support could all distort both safety and interpretation. By limiting the cohort, the study improves its ability to detect a true treatment effect in a population where the kidney insult is tied directly to surgery and bypass rather than to a separate chronic process.
The First Test of a Familiar Hospital Fluid in a New Role
The study uses an amino acid solution that is already familiar in pediatric hospitals as part of intravenous nutrition. Its repurposing here is the point. A compound that is routine in one setting is being asked to serve a very different purpose: perioperative renal protection.
That shift raises the central question for pediatric cardiac care teams. Can a standard nutrition product, given at a specific dose and time window, reduce postoperative kidney injury enough to change recovery after complex heart surgery?
The answer will depend on whether the biologic signal appears in both creatinine-defined AKI and urinary biomarkers, and whether any renal effect translates into better postoperative recovery across the 90-day follow-up window. With estimated enrollment of 270 children and completion projected for 2032, the trial is positioned to provide an important pediatric test of a strategy that has already shown adult promise but has not yet been validated in children undergoing bypass.