Amino Acid Infusion for Kidney Protection in Cardiac Surgery Patients with Chronic Kidney Disease: A Secondary Analysis of the PROTECTION Trial

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Background: In the PROTECTION trial, intravenous amino acids (AA) decreased the occurrence of acute kidney injury (AKI) in cardiac surgery patients with cardiopulmonary bypass (CPB). Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease (CKD) have diminished renal functional reserve, and AA may be less protective in such patients. Thus, a separate investigation of such patients is warranted. Methods: We defined CKD as an estimated glomerular filtration rate (eGFR)<60 mL·min-1·1.73 m-2 and patients with eGFR≥60 mL·min-1·1.73 m-2 served as controls. The primary outcome was the occurrence of AKI. Secondary outcomes included severity of AKI, need for and duration of renal replacement therapy, and all-cause mortality. Results: Among CKD patients (n=812), compared with placebo, AA significantly decreased the rate of AKI (43.1% vs 50.3%; RR, 0.86; 95%CI, 0.74 to 0.99; p=0.041; number needed to treat [NNT]=14) with a median percentage increase in eGFR from baseline to postoperative day three of 12.7% vs. 6.5% (p=0.002). In eGFR-based CKD subgroups (30 to 39, 40 to 49, and 50 to 59 mL·min-1·1.73 m-2) the AA effect was similar (interaction p=0.50). Finally, AA infusion decreased the occurrence of severe (stage 3) AKI (2.7% vs. 5.6%; RR 0.48; 95%CI, 0.24 to 0.98; p=0.038). Conclusions: AA infusion protected CKD patients undergoing CPB from developing AKI, with an absolute risk reduction of 7% and a NNT of 14 in a cohort with a >45% rate of AKI. Moreover, it delivered a >50% relative risk reduction in severe AKI.