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.

OBJECTIVES: In cardiac surgery patients, acute kidney injury (AKI) frequently occurs in the setting of haemodynamic instability and treatment with temporary mechanical circulatory support (tMCS). Recent evidence suggests amino acids (AA) infusion may reduce AKI rate. However, the effect of AA infusion in patients requiring tMCS may be less effective. METHODS: We performed a secondary analysis of the PROTECTION multicentre randomized controlled trial including all patients treated with tMCS. Patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive 2 g/kg ideal body weight/day of intravenous AA to a maximum of 100 g/day or matching placebo from operating room admission until up to 3 days, receipt of renal-replacement therapy, discharge from ICU or death. The primary outcome of the PROTECTION study was the rate of AKI, as in this secondary analysis. A total of 3511 patients were randomized in the study. RESULTS: We studied 232 patients who received tMCS, 112 randomized to AA infusion and 120 to placebo. The median preoperative serum creatinine value was significantly higher among AA group patients (AA: 1.08, interquartile range 0.90–1.26; placebo: 0.98, interquartile range 0.85–1.15; P = 0.02). The rate of AKI, however, was lower in patients randomized to AA (44.6% vs 60.8%; relative risk 0.73; 95% confidence interval (0.57–0.94); P = 0.01; number needed to treat = 6). We found no significant differences in secondary outcomes. CONCLUSIONS: Short-term AA infusion appears to reduce rate of AKI among patients requiring tMCS. Use of AA in this population at high-risk for renal failure appears justified. Clinical trial registration number: ClinicalTrials.gov NCT03709264.

Objectives: The impact of acute kidney injury (AKI) on long-term outcomes of hospital survivors is controversial. We conducted a systematic review and meta-analysis of all studies reporting such outcomes in patients with AKI and including a control population. Data Sources: We included original studies published in peer-reviewed journals that compared long-term outcomes (survival, need for dialysis, chronic kidney disease [CKD]) among hospitalized patients with vs. without AKI. Study Selection: Pertinent articles enrolled patients who experienced and survived a defined episode of AKI, included a control group without AKI, and reported at least one long-term outcome (mortality, dialysis, or CKD), with a minimum follow-up of 1 year. Data Extraction: Two independent investigators extracted data on study characteristics, patient populations, follow-up duration, and long-term outcomes. Discrepancies were resolved by consensus. Data Synthesis: We identified 14 studies for a total of 1,058,109 overall matched patients with a median duration of follow-up of 3 years. Patients who experienced an episode of AKI and survived hospital discharge had a significant increase in long-term mortality at the longest follow-up available for each study (137,506/519,672 [26.4%] vs. 93,702/530,663 [17.6%]; relative risk [RR], 1.42; 95% CI, 1.13–1.78; p = 0.002), compared with controls. They also had a greater risk of receiving dialysis (1,928/42,529 [4.5%] vs. 854/42,529 [2.0%]; RR, 2.48; 95% CI, 1.79–3.43; p < 0.001), and of developing CKD (2,956/5,739 [51.5%] vs. 2,902/7,781 [37.3%]; RR, 1.71; 95% CI, 1.33–2.19; p < 0.001). Conclusions: Compared with controls, patients who experienced an episode of AKI and survived to hospital discharge have an increased risk of death, dialysis, and CKD.