The implementation of a nephroprotective prevention care strategy significantly reduced the risk for acute kidney injury (AKI) following major surgery among high-risk patients, according to a new randomized trial.

“Compared with usual care, in major surgery patients at high risk for AKI, a KDIGO-recommended preventive care strategy significantly decreased the occurrence of moderate or severe AKI within 72 hours of surgery,” the authors concluded in research published in The Lancet.

AKI is a common complication after major surgery, often caused by hemodynamic changes and exposure to nephrotoxic agents. It is associated with increased risk for morbidity and mortality, as well chronic kidney disease (CKD).

Although clinical guidelines recommend AKI preventive strategies, including bundled care approaches, adherence is often difficult due to time and resource constraints, among other hindrances.

BigpAK-2: A Multi-National Trial

Given the heightened risk among vulnerable patients, the investigators sought to evaluate the potential benefits of a preventive care intervention based on guideline recommendations from Kidney Disease: Improving Global Outcomes (KDIGO).

The BigpAK-2 multicenter trial was conducted at 34 hospitals in Europe. Researchers included 1176 patients undergoing major surgery and identified as being at high risk for AKI based on clinical risk factors and assessment of biomarkers including urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein.

The patients (approximately 33% women) were randomized prior to surgery from November 2020 to June 2024 to receive either usual care (n = 591) or the KDIGO-recommended preventive care strategy (n = 589).

The KDIGO preventive strategy consisted of advanced hemodynamic monitoring, optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs and radiocontrast agents, and prevention of hyperglycemia.

The two groups were well-balanced for baseline characteristics, ICU admission variables, surgical interventions, and intraoperative management.

KDIGO’s Significant Impact

The primary endpoint, moderate or severe AKI within 72 hours of surgery, occurred significantly less often in the prevention strategy group compared with the usual care group (14.4% vs 22.3%; odds ratio [OR], 0.57; P = .0002), corresponding to a number needed to treat of 12.

Rates of AKI of any stage were also lower in the prevention group (36.7% vs 40.9%; OR, 0.78). Persistent moderate or severe AKI occurred in 39.0% of the prevention group and 44.5% of usual care group (OR, 0.71), with the effects consistent in intention-to-treat, per-protocol, and as-treated analyses.

Multivariate analysis showed that the strongest contributors to reduced risk for moderate-to-severe AKI were the prevention of hypotension (OR, 0.19; P = .001) and discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (OR, 0.36; P = .002).

There were no significant differences between the groups in other secondary outcomes, and no differences in terms of adverse events.

The most common adverse events were atrial fibrillation (8.8% in the intervention group vs 9.7% in the usual care group), hemodynamically relevant arrhythmias (7.2% vs 8.6%), significant bleeding or hemorrhage (6.0% vs 5.3%), and unplanned return to the operating room (5.1% vs 6.5%).

Implementation and Clinical Implications

All components of the KDIGO-recommended nephroprotective strategy were implemented in 46.9% of patients, increasing to 62.7% after tight glycemic control was excluded. Co-author John A. Kellum, MD, noted this level of adherence is “much higher than other studies examining care bundles.”

“The study did not mandate the use but rather recommended that each step [in the prevention strategy] be considered,” Kellum, a distinguished professor and director of the Center for Critical Care Nephrology at University of Pittsburgh, Pittsburgh, told Medscape Medical News. “Physicians were free to use their judgement for individual cases.”

Kellum added that this is the first large multi-center study of its kind to evaluate AKI prevention in high-risk surgical patients, including both cardiac and noncardiac surgery.

Biomarker-Enabled Strategy Is Key

The authors emphasized the importance of using a biomarker-based strategy to identify high-risk patients most likely to benefit from prevention and allowing for targeted treatment algorithms.

“For clinical practice, this approach avoids exposing patients to interventions that they cannot benefit from and improves cost-effectiveness,” they wrote. “The combination of such biomarkers with clinical risk factors further improves such enrichment strategies.”

Patients with CKD stage IV to V were excluded due to a lower likelihood that their risk could be modified, representing a key limitation.

Nevertheless, Kellum noted that the findings still provide a clear takeaway message for clinicians.

“AKI can be prevented by providing the KDIGO bundle,” he said. “The efficacy is quite good when applied to high-risk patients as identified by the biomarkers.”

Study ‘Reaffirms’ Benefits of Detail-Oriented Protocols

Commenting on the study for Medscape Medical News, Sergio D. Bergese, MD, professor of anesthesiology and neurological surgery and director of Outcomes and Clinical Research in Perioperative Medicine at Stony Brook University, New York City, noted that “this type of data reaffirms the importance of attention to details in perioperative medicine and how a well-designed protocol, and protocols in general, can help our patients.”

Although the preventive strategy used reflects a standard approach, Bergese noted that the results provide a compelling argument that can be used to strengthen practice recommendations going forward.

“The big finding is how effective the study was in controlling all of the parameters,” he said. “Further research is required to investigate implementation of preventive strategies in different settings as well as to see if all of the strategies are needed, but the findings at the end of the day are not unexpected.”

Kellum reported having had royalty, stock, patent and/or honoraria relationships with CytoSorbents, Klotho, bioMérieux, J3RM, Spectral Medical, AstraZeneca, Bayer, Novartis, Mitsubishi Tenabe, and Chugai Pharma. Bergese had no disclosures to report.