A Randomized Trial of Intravenous Amino Acids for Kidney Protection

23 February 2025
Dr Fahd Al Qureshah
دور الأحماض الأمينية الوريدية لحماية الكلى

Amino Acids for Kidney Protection

Background

Acute kidney injury (AKI) is a prevalent and severe complication of cardiac surgery, often resulting from reduced kidney perfusion. Patients with AKI have an increased risk of chronic kidney disease, higher hospitalization costs, and elevated mortality rates. Currently, there is no single intervention that effectively prevents AKI in cardiac surgery patients beyond general supportive measures. Previous research has indicated that intravenous amino acid infusions may improve kidney perfusion and recruit renal functional reserve, but their effectiveness in reducing AKI after cardiac surgery remains uncertain. This study aimed to determine whether amino acid infusion reduces the incidence of AKI in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods

The PROTECTION trial was a multinational, double-blind, randomized, placebo-controlled study conducted at 22 centers in three countries. A total of 3,511 adult patients scheduled for cardiac surgery were randomized into two groups:

  • The amino acid group (n = 1,759) received a balanced mixture of amino acids at a dose of 2 g/kg of ideal body weight per day for up to three days.
  • The placebo group (n = 1,752) received Ringer’s solution as an infusion following the same protocol.

The primary outcome was the incidence of AKI, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. Secondary outcomes included AKI severity, the need for kidney replacement therapy (KRT), and 30-day all-cause mortality.

Blinding was ensured throughout the study, with patients, physicians, investigators, and data collectors unaware of group assignments. Statistical analyses followed an intention-to-treat approach, with subgroup and sensitivity analyses conducted.

Results

  • AKI occurred in 474 patients (26.9%) in the amino acid group and 555 patients (31.7%) in the placebo group (Relative Risk [RR], 0.85; 95% Confidence Interval [CI], 0.77–0.94; P = 0.002).
  • Stage 3 AKI (the most severe form) occurred in 29 patients (1.6%) in the amino acid group and 52 patients (3.0%) in the placebo group (RR, 0.56; 95% CI, 0.35–0.87).
  • Kidney replacement therapy (KRT) was required in 24 patients (1.4%) in the amino acid group and 33 patients (1.9%) in the placebo group (RR, 0.73; 95% CI, 0.43–1.22).
  • No significant differences were observed in 30-day mortality (2.8% in both groups), length of ICU stay, duration of mechanical ventilation, or total hospital stay.
  • Adverse events were similar between both groups, with no safety concerns related to amino acid infusion.

Discussion

The study provides strong evidence that intravenous amino acid infusion significantly reduces the incidence and severity of AKI in cardiac surgery patients without increasing adverse events. The risk of AKI was reduced by 15%, and the risk of severe (stage 3) AKI was reduced by 44% in the amino acid group.

Several mechanisms may explain these findings:

  1. Increased renal perfusion: Amino acids stimulate kidney blood flow by reducing afferent arteriolar resistance and enhancing nitric oxide synthesis, leading to better renal oxygenation and filtration.
  2. Recruitment of renal functional reserve: This improves the kidneys' ability to handle metabolic stress following surgery.
  3. Improved glomerular filtration rate (GFR): Consistent with findings from previous animal and human studies.

Despite these benefits, amino acid infusion did not significantly impact kidney replacement therapy rates, mortality, or ICU stay, suggesting that while it prevents AKI, it does not necessarily improve overall patient survival or long-term kidney function.

Limitations

  • The study only included high-income countries, limiting its applicability to low- and middle-income regions where healthcare access differs.
  • The diagnosis of AKI was based only on serum creatinine levels, not including biomarkers of kidney injury, which could have provided additional insights.
  • While renal biopsies could have clarified the underlying mechanisms, they were not ethically feasible in a surgical population.
  • The trial did not mandate a standardized AKI prevention protocol, which may have introduced variability in patient management.

Conclusions

Among adult patients undergoing cardiac surgery, intravenous amino acid infusion significantly reduced the occurrence of AKI, particularly in severe cases, without increasing adverse events. Given the high incidence of AKI after cardiac surgery, amino acid infusion may represent a simple, low-risk, and effective intervention for kidney protection. Further studies are needed to assess its long-term impact on chronic kidney disease progression and survival.

Key Statistics

  • Total patients enrolled: 3,511
  • AKI incidence: 26.9% (amino acid group) vs. 31.7% (placebo group), P = 0.002
  • Stage 3 AKI: 1.6% vs. 3.0%, P = 0.01
  • Kidney replacement therapy: 1.4% vs. 1.9%, P = 0.16
  • 30-day mortality: 2.8% vs. 2.8%, P = 0.98
  • Relative risk reduction of AKI: 15%

This trial supports amino acid infusion as a preventive strategy for AKI in cardiac surgery patients and encourages future research on its long-term benefits.

For full details, refer to the original article: https://pubmed.ncbi.nlm.nih.gov/38865168/