A preventive care strategy based on Kidney Disease: Improving Global Outcomes recommendations reduced moderate to severe acute kidney injury within 72 hours following major surgery, according to findings from the multicenter, randomized BigpAK-2 trial.
Of 7,873 patients screened, 1,180 (15%) met eligibility criteria and were randomly assigned across 34 hospitals in Europe, highlighting the targeted nature of the biomarker-guided approach.
Moderate to severe acute kidney injury (AKI) occurred in 14% of patients in the intervention group compared with 22% in the control group, corresponding to 0.57 times the odds of the outcome and a number needed to treat of 12. Although reductions were observed using both urine output and serum creatinine criteria, most AKI diagnoses were driven by urine output. Reductions in creatinine-defined AKI (6% vs 10%) were also observed.
Study Design and Intervention
Eligible patients were aged 18 years or older and had at least one clinical risk factor for AKI, including age 75 years or older, vasopressor or mechanical ventilation use, stage 3 chronic kidney disease, or intraoperative use of radiocontrast, along with a urinary TIMP-2×IGFBP7 concentration of at least 0.3 measured within 4 to 18 hours following surgery.
The preventive care strategy included hemodynamic optimization using repeated assessment of fluid responsiveness with passive leg raising performed at least every 3 hours. A positive response, defined as a cardiac output increase greater than 10%, prompted administration of a 500 to 1,000 mL balanced crystalloid bolus.
The protocol also targeted a mean arterial pressure of at least 65 mmHg and a cardiac index of at least 2.5 L/min per m² with vasopressors or inotropes as needed. Additional components included discontinuation of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, avoidance of nephrotoxic drugs, and maintenance of blood glucose concentrations between 100 mg/dL and 150 mg/dL.
Outcomes and Safety
Any-stage AKI occurred in 37% of patients in the intervention group compared with 41% in the control group.
Among patients with moderate to severe AKI, persistent AKI lasting more than 48 hours occurred in 39% of patients in the intervention group compared with 45% in the control group.
Major adverse kidney events at 90 days occurred in approximately 11% of patients in each group. Mortality at 30 days and 90 days was also similar between groups.
Rates of adverse events, including atrial fibrillation, arrhythmias, bleeding, and reoperation, did not differ between groups.
Subgroup Analyses
The preventive effect was directionally consistent across surgical, sex, chronic kidney disease, and early biomarker measurement subgroups.
Multivariable analysis showed that avoidance of hypotension and discontinuation of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers had the strongest association with the primary outcome.
Implementation and Limitations
Implementation of all components of the preventive strategy occurred in 47% of patients. When strict glycemic control was excluded, adherence increased to 63%, reflecting the difficulty of maintaining glucose targets and the mixed evidence supporting this component.
The trial was open-label, and the study population may not be generalizable to settings with different resources, geographic regions, or patient populations. Patients with advanced chronic kidney disease were not included, and outcomes in biomarker-negative patients were not assessed.
The study was not powered to detect differences in long-term outcomes. Investigators estimated that more than 8,000 patients would be required to detect a meaningful difference in major adverse kidney events at 90 days, helping to explain why these outcomes were similar between groups.
The intervention also required urinary catheters, central venous access, and cardiac index monitoring technologies, which may not be readily available in all clinical settings and could limit broader adoption.
Commentary
“[C]ompared with usual care, in major surgery patients at high risk for AKI, as identified by urinary TIMP-2×IGFBP7 together with clinical risk factors, a [Kidney Disease: Improving Global Outcomes]-recommended preventive care strategy significantly decreased the occurrence of moderate or severe AKI within 72 h of surgery,” wrote lead study researcher Alexander Zarbock, MD, of the Department of Anesthesiology of Intensive Care and Pain Medicine at the University Hospital Münster in Germany, and colleagues.
“[R]einforce that excellent supportive care, when applied to a high-risk surgical population, can reduce the risk for AKI and that improving the process of care strategies to prevent this common condition cannot be overlooked in an area in need of effective treatments,” wrote Edward D Siew, MD, of the Division of Nephrology and Hypertension at Vanderbilt University Medical Center in Tennessee, and the Tennessee Valley Healthcare System at Nashville Veterans Affairs Hospital in Tennessee, in an accompanying commentary.
Full disclosures can be found in the study and commentary.
Source: The Lancet Study, Commentary
