Amino Acids

In the PROTECTION trial (Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery), intravenous amino acids decreased the occurrence of acute kidney injury in cardiac surgery patients with cardiopulmonary bypass. Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease have diminished renal functional reserve, and amino acids may be less protective in such patients. Thus, a separate investigation of such patients is warranted.

For this study chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml · min−1 · 1.73 m−2, and patients with estimated glomerular filtration rates greater than or equal to 60 ml · min−1 · 1.73 m−2 served as controls. The primary outcome was the occurrence of acute kidney injury. Secondary outcomes included severity of acute kidney injury, need for and duration of renal replacement therapy, and all-cause mortality.

Among chronic kidney disease patients (n = 812), compared with placebo, amino acids significantly decreased the rate of acute kidney injury (43.1% vs 50.3%; relative risk, 0.86; 95% CI, 0.74 to 0.99; P = 0.041; number needed to treat = 14) with a median percentage increase in estimated glomerular filtration rate from baseline to postoperative day 3 of 12.7% versus 6.5% (P = 0.002). In estimated glomerular filtration rate–based chronic kidney disease subgroups (30 to 39, 40 to 49, and 50 to 59 ml · min−1 · 1.73 m−2), the amino acid effect was similar (interaction P = 0.50). Finally, amino acid infusion decreased the occurrence of severe (stage 3) acute kidney injury (2.7% vs. 5.6%; relative risk 0.48; 95% CI, 0.24 to 0.98; P = 0.038).

Amino acid infusion protected chronic kidney disease patients undergoing cardiopulmonary bypass from developing acute kidney injury, with an absolute risk reduction of 7% and a number needed to treat of 14 in a cohort with a greater than 45% rate of acute kidney injury. Moreover, it delivered a greater than 50% relative risk reduction in severe acute kidney injury.

Acute Kidney Injury (AKI) is a common complication after cardiac surgery affecting up to 40% leading to increased morbidity and mortality. To date, there is no specific treatment for AKI, thus, clinical research efforts are focused on preventive measures. The only pharmacological preventive intervention that has demonstrated a beneficial effect on AKI in a high-quality, double-blind, randomized controlled trial is a short perioperative infusion of a balanced mixture of amino acid solution. Amino acid infusion reduced the incidence of AKI by recruiting renal functional reserve and, therefore, increasing the glomerular filtration rate. The beneficial effect of amino acids was further confirmed for severe AKI and applied to patients with chronic kidney disease. Among non-pharmacological interventions, international guidelines on AKI suggest the implementation of a bundle of good clinical practice measures to reduce the incidence of perioperative AKI or to improve renal function whenever AKI occurs. The Kidney Disease Improving Global Outcomes (KDIGO) bundle includes the discontinuation of nephrotoxic agents, volume status and perfusion pressure assessment, renal functional hemodynamic monitoring, serum creatine, and urine output monitoring, and the avoidance of hyperglycemia and radiocontrast procedures. However, pooled data from a meta-analysis did not find a significant reduction in AKI. The aim of this review is to delineate the most appropriate evidence-based approach to prevent AKI in cardiac surgery patients.