Delayed Remote Ischemic Preconditioning Reduces Contrast-Associated Acute Kidney Injury After Coronary Angiography and PCI: Insights from a Randomized Trial

Highlight

• Delayed remote ischemic preconditioning (RIPC) 24 hours before coronary angiography or PCI significantly reduces contrast-associated acute kidney injury (CA-AKI) incidence in at-risk patients.
• RIPC delivers four cycles of 5-minute ischemia via upper arm cuff inflation, offering a non-invasive kidney-protective strategy.
• No significant differences were observed in secondary outcomes such as renal replacement therapy and mortality, warranting larger studies.
• This approach could alter pre-procedural preventive strategies for patients at risk of CA-AKI.

Study Background and Disease Burden

Contrast-associated acute kidney injury (CA-AKI) is a common and serious complication following coronary angiography (CAG) and percutaneous coronary intervention (PCI), both widely performed interventions for coronary artery disease. CA-AKI not only increases short-term morbidity and hospitalization length but also contributes to long-term adverse outcomes, including increased mortality risk. Currently, effective preventive measures against CA-AKI are limited, and there remains an unmet clinical need for safe, practical, and effective kidney-protective interventions in this setting.

Remote ischemic preconditioning (RIPC) is a non-invasive procedure that induces transient ischemia in distant tissues (typically a limb) to confer organ protection, potentially through release of circulating protective factors and modulation of inflammatory pathways. Although previous research has suggested benefits when RIPC is applied shortly before angiographic contrast exposure, the efficacy of delayed RIPC—performed hours to a day prior—has remained unclear. Understanding whether delayed RIPC reduces CA-AKI could expand the utility and feasibility of this prophylactic intervention in clinical practice.

Study Design

This multicenter, randomized, controlled trial enrolled 501 patients at increased risk for CA-AKI undergoing elective CAG or PCI. Patients were randomized to receive either “delayed RIPC”—consisting of four cycles of 5-minute inflation-induced ischemia applied to one upper arm 24 hours before their procedure—or a sham control procedure without actual cuff inflation.

The primary endpoint was the incidence of AKI within the post-procedural period, defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, which consider relative serum creatinine changes and urine output measures. Key secondary endpoints included the need for renal replacement therapy (dialysis) during hospitalization, changes in urinary biomarkers indicative of kidney injury, and clinical outcomes by 90 days post-procedure such as non-fatal myocardial infarction, stroke, rehospitalization, and all-cause mortality.

Key Findings

Of the 501 randomized patients (median age 74 years), 467 (93.2%) completed 90-day follow-up. In the delayed RIPC group, the incidence of CA-AKI was 3.2%, compared to 7.6% in the sham group, representing a statistically significant reduction (odds ratio 0.4; 95% confidence interval 0.17–0.94; P = .03).

While these findings suggest nearly a 60% relative risk reduction in CA-AKI with delayed RIPC, the trial was underpowered for secondary outcomes, showing no significant differences in renal replacement therapy use, urinary biomarker changes, or 90-day major adverse cardiovascular events and mortality.

The intervention was well tolerated with no reported adverse events directly attributable to the RIPC procedure. Patient characteristics, comorbidities, and procedural details were well balanced between groups, minimizing bias.

Expert Commentary

This study adds important evidence supporting a potentially practical and feasible approach to CA-AKI prevention through delayed RIPC. The 24-hour pre-procedural timeframe broadens flexibility for clinical application, as interventions could be scheduled in advance rather than exclusively immediately before contrast exposure.

The biological plausibility of RIPC’s protective effects includes promotion of systemic anti-inflammatory pathways, enhancement of endogenous antioxidant defenses, and potential endothelial conditioning that reduces ischemia-reperfusion injury. The limb ischemic stimulus may release circulating mediators that condition the kidneys and heart at a distance.

Nevertheless, limitations include the modest overall event rate, limiting statistical power for secondary outcomes and long-term clinical benefits. The trial’s single blinded design and reliance on a sham procedure might introduce some placebo effect, although the objective biochemical endpoints lessen this concern. Additionally, the studied population was relatively elderly and at elevated baseline risk, so generalizability to younger or lower-risk cohorts requires further study.

Current guidelines recognize the need for effective preventive strategies for CA-AKI but have not yet incorporated delayed RIPC due to limited evidence. This trial supports further large-scale randomized studies to validate findings and explore impact on patient-centered outcomes, healthcare utilization, and cost-effectiveness.

Conclusion

Delayed remote ischemic preconditioning performed 24 hours before elective coronary angiography or PCI significantly lowers the incidence of contrast-associated acute kidney injury in patients at risk. This non-invasive, low-cost strategy has promising clinical implications as an adjunctive prophylactic intervention.

Further trials with larger sample sizes and longer follow-up are warranted to confirm the benefits, evaluate effects on cardiovascular and renal outcomes, and integrate RIPC optimally into clinical pathways to reduce CA-AKI burden and improve patient prognosis.

References

Jia P, Zhao G, Huang Y, Zou Z, Zeng Q, Chen W, Ren T, Li Y, Wang X, Kang T, Liu Z, Ma M, Yu J, Wu Q, Deng B, Yan X, Wan X, Chen X, Cao C, Ge J, Ding X. Remote ischaemic pre-conditioning, kidney injury, and outcomes after coronary angiography and intervention: a randomized trial. Eur Heart J. 2025 Jun 9;46(22):2066-2075. doi: 10.1093/eurheartj/ehaf135. PMID: 40067773.