A Novel Technique to Reduce Kidney Injury by Maintaining Na/K Pump Functions Using Electric Energy

Abstract

Renal ischemia‐reperfusion injury is an important contributor to the development of delayed graft function, which is associated with higher rejection rates and worse long‐term outcomes of the allografts. One of the earliest impairments during ischemia is insufficient ATP supply‐induced Na/K pump dysfunction, which results in subsequent cellular damage. Consequently, strategies that preserve ATP levels or Na/K pump function may limit the extent of renal injury during ischemia‐reperfusion.In this study, we developed a novel technique that applies an oscillating electrical field to first synchronize the pump molecules, and then modulate their pumping rates. We dubbed this technique as the synchronization modulation electric field. We present this novel technique of using electric energy to substitute ATPs in fueling and activating the pumps, thereby efficiently maintaining cellular functions under ATP insufficient conditions. We tested the effectiveness of this technique in two kinds of models of ischemic renal injury: an in situ renal ischemia‐reperfusion injury model (predominantly warm ischemia) and kidney transplantation rodent and swine models (predominantly cold ischemia).Our results show that application of the specially designed electric field effectively delayed ATP depletion during ischemia and preserves Na/K pump activity, thereby alleviating kidney injury by about 45% (plasma creatinine of 1.17±0.04 and 1.97±0.06 mg/dL for electric field treated and untreated groups, respectively) and improving renal allograft function by over 50% compared with the controls.This novel technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury, but also for other diseases associated with dysfunction of Na/K pumps.