1. Publication
- Title: A preventive care strategy to reduce moderate or severe acute kidney injury after major surgery (BigpAK-2): a multinational, randomised clinical trial
- Acronym: BigpAK-2
- Year & Journal: The Lancet, epublished November 13, 2025 (print: 2025;406(10521):2782-2791)
- Citation: Zarbock A, Ostermann M, Forni L, et al; BigpAK-2 study group. Lancet. 2025;406(10521):2782-2791. doi:10.1016/S0140-6736(25)01717-9
2. Context & Rationale
Background: AKI is a common complication of major surgery, but recommended KDIGO preventive care is rarely actually administered, despite prior smaller trials (BigpAK, PrevAKI-multicenter) suggesting biomarker-guided implementation reduces AKI.
Research Question/Hypothesis: In adults at high risk of AKI (identified via urinary biomarkers) undergoing major surgery, does a KDIGO-based preventive care strategy reduce moderate-or-severe AKI within 72 hours compared with usual care?
Why This Matters: Tests, at larger multinational scale, whether biomarker-guided implementation of already-known but underused preventive measures reduces a common, morbid perioperative complication.
3. Design & Methods
- Study Type: Multinational, multicenter, randomized clinical trial
- Setting & Centers: 34 hospitals, Europe
- Population: Adults undergoing major surgery, high-risk for AKI via urinary biomarkers
- Intervention: KDIGO-guideline-based preventive care bundle (supportive measures, nephrotoxin avoidance), 72h post-surgery
- Comparator: Usual care
- Randomization: 1176 patients total
- Blinding: Not detailed (likely open-label care-bundle intervention)
- Statistical Power & Follow-Up: Primary outcome: moderate/severe AKI within 72h. Adaptive design with interim sample-size recalculation.
4. Key Results
Outcome | Preventive Care | Usual Care | p-value | Notes |
Moderate/severe AKI within 72h (primary) | 14.4% | 22.3% | 0.0002 | Significant reduction |
Adverse events | No significant increase | — | — | Safety maintained |
5. Internal Validity Assessment
- Randomization & Allocation: Multinational randomization across 34 hospitals; concealment mechanics not detailed.
- Protocol Adherence & Separation: Biomarker-guided risk stratification plus protocolized bundle implementation.
- Blinding & Detection Bias: Likely open-label; AKI is a relatively objective endpoint (creatinine/urine-output criteria).
- Overall Internal Validity Conclusion: Strong — large, statistically robust (P=0.0002), no safety penalty; builds on positive predecessor trials.
6. External Validity Assessment
- Population Representativeness: Broad, multinational European surgical population, biomarker-selected high-risk.
- Practice Context: Requires urinary biomarker testing capability.
- Overall External Validity Conclusion: Good for major-surgery populations in health systems with biomarker-testing capability.
7. Strengths & Limitations
Strengths: Large, multinational, highly significant result; builds on BigpAK/PrevAKI-multicenter; no adverse-event increase; addresses documented implementation gap.
Limitations: Requires biomarker infrastructure; likely open-label; Europe-only generalizability.
8. Interpretation & Practice Impact
- Clinical Implications: Supports biomarker-guided KDIGO bundle implementation in high-risk surgical patients.
- Mechanistic Coherence: Actually implementing known-good practices (not just recommending them) produces measurable benefit.
- Systems-Level Takeaway: Supports investment in biomarker testing and structured perioperative bundle programs.
9. Controversies & Subsequent Evidence
Builds directly on the same group's BigpAK (2018) and PrevAKI-multicenter (2021) trials — a cumulative evidence program. Directly operationalizes existing KDIGO guidelines.
10. Summary & Executive Takeaway
Summary: BigpAK-2 randomized 1176 high-AKI-risk surgical patients across 34 European hospitals to a KDIGO-based preventive bundle or usual care. Moderate/severe AKI within 72h fell from 22.3% to 14.4% (P=0.0002), no safety penalty.
Overall Takeaway: Biomarker-guided KDIGO bundle implementation significantly reduces postoperative AKI without safety cost — a practical, actionable perioperative quality-improvement target confirmed at multinational scale.
11. Bibliography
- Meersch M, Schäfer ST, Weiss R, et al. BigpAK. Ann Surg. 2018;267:1013-1020.
- Zarbock A, Küllmar M, Ostermann M, et al. PrevAKI-multicenter. Anesth Analg. 2021;133:292-302.