Reducing ischemic kidney injury through application of a synchronization modulation electric field to maintain Na+/K+-ATPase functions.

Renal ischemia-reperfusion injury is an important contributor to the development of delayed graft function after transplantation, which is associated with higher rejection rates and poorer long-term outcomes. One of the earliest impairments during ischemia is Na⁺/K⁺-ATPase (Na/K pump) dysfunction due to insufficient ATP supply, resulting in subsequent cellular damage. Therefore, strategies that preserve ATP or maintain Na/K pump function may limit the extent of renal injury during ischemia-reperfusion. Here, we applied a synchronization modulation electric field to activate Na/K pumps, thereby maintaining cellular functions under ATP-insufficient conditions. We tested the effectiveness of this technique in two models of ischemic renal injury: an in situ renal ischemia-reperfusion injury model (predominantly warm ischemia) and a kidney transplantation model (predominantly cold ischemia). Application of the synchronization modulation electric field to a renal ischemia-reperfusion injury mouse model preserved Na/K pump activity, thereby reducing kidney injury, as reflected by 40% lower plasma creatinine (1.17 ± 0.03 mg/dl) in the electric field–treated group as compared to the untreated control group (1.89 ± 0.06 mg/dl). In a mouse kidney transplantation model, renal graft function was improved by more than 50% with the application of the synchronization modulation electric field according to glomerular filtration rate measurements (85.40 ± 12.18 μl/min in the untreated group versus 142.80 ± 11.65 μl/min in the electric field–treated group). This technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury but also for other diseases associated with Na/K pump dysfunction due to inadequate ATP supply. Electrically inhibiting ischemic damage: Organ ischemia can lead to insufficient ATP supplies, resulting in Na⁺/K⁺-ATPase dysfunction and cell damage. Here, Chen and colleagues applied a synchronization modulation electric field to rodent kidneys to maintain Na⁺/K⁺-ATPase function during ischemia. The technique first synchronizes the Na⁺/K⁺-ATPases and then applies electric energy to run the pumps, producing an ATP molecule with each pumping cycle. The pumping rates can be modulated either up or down and then maintained at the target rate. In mouse models of warm and cold ischemia, the technique decreased kidney injury and improved function, and application of the technique to human kidneys during cold storage decreased histological evidence of injury, suggesting that the approach might be useful in minimizing allograft dysfunction. [ABSTRACT FROM AUTHOR]