International Perfusion Association

Kidney Injury Under Diminished Pulsatile Flow Induced by V-A ECMO in Sheep

Extracorporeal membrane oxygenation (ECMO) is a lifesaving intervention used for critically ill patients, yet it is frequently associated with high incidences of kidney injury. This study, published in the International Journal of Medical Sciences, aimed to assess the effects of diminished pulsatile blood flow induced by veno-arterial ECMO (V-A ECMO) on kidney function compared to normal pulsatile flow under veno-venous ECMO (V-V ECMO).

The Experiment:

Ten healthy sheep were divided into two groups: five underwent V-A ECMO, and five underwent V-V ECMO. Over seven days, vital signs were monitored every six hours, while renal biomarkers were assessed every 24 hours. The study focused on key renal function indicators such as blood urea nitrogen (BUN), creatinine (Cr), and cystatin C (CyC), alongside endothelial markers like CD31 and renin expression.

Key Findings:

• Blood Flow Characteristics: In the V-A ECMO group, pulse pressure (PP) was reduced to around 20 mmHg, whereas in the V-V ECMO group, it remained higher at approximately 30 mmHg. The pulsatility index (PI) was significantly lower in the V-A ECMO group (<0.25), indicating diminished pulsatile flow.

  • Renal Function Markers: BUN and Cr levels remained similar across both groups. However, cystatin C (CyC) was significantly elevated in the diminished pulsatile flow group, indicating early kidney dysfunction despite normal conventional biomarkers.
  • Endothelial Cell Markers: The expression of CD31, a marker of endothelial health, was significantly lower in the V-A ECMO group. Additionally, renin-positive glomeruli ratios were reduced, suggesting an impaired renin-angiotensin system response.
  • Tissue Analysis: Both groups exhibited signs of early-stage kidney injury, such as protein accumulation in renal sacs and mild tubule hypoxia. The presence of hypoxia-inducible factor-1α (HIF-1α) in renal tubules indicated that hypoxia was occurring in both groups, regardless of ECMO type.

Clinical Implications:

These findings suggest that diminished pulsatile flow under V-A ECMO leads to early-stage kidney injury, even when traditional renal function markers appear normal. While serum BUN and Cr levels remained stable, elevated CyC levels and decreased CD31 expression indicated a decline in renal health at the cellular level. This underscores the importance of maintaining adequate pulsatile flow during ECMO therapy to preserve renal function.

Future Research Directions:

Given that ECMO is widely used in critical care settings, further research is needed to determine optimal pulsatility levels for renal protection. Additionally, exploring energy-related formulas for pulsatility measurement and assessing long-term kidney function post-ECMO could provide valuable insights. Understanding the reversibility of early kidney injuries observed in this study would also be crucial for improving patient outcomes.

This research highlights the necessity of re-evaluating ECMO management strategies to mitigate kidney injury risks. Clinicians should consider pulsatility as a key factor in optimizing ECMO support and preventing long-term renal complications.

Study Ranking: 4 (High Quality)  The study employs a well-structured experimental design using an animal model, provides detailed physiological measurements, and presents clinically relevant findings, though further human studies are needed for direct clinical application.