Mild Electrical Stimulation and Heat Shock Promotes Recovery from AKI in Mice

Background: AKI had been considered as a “curable disease”, but recent epidemiological studies and meta-analysis have revealed that AKI is a risk factor for CKD. Therefore, establishing a treatment that can promote recovery from AKI to control the AKI to CKD transition is needed. We previously showed that mild electrical stimulation (MES) and heat shock (HS) suppressed albuminuria and proteinuria in adriamycin-induced nephrotic syndrome in mice. We also showed that MES+HS is renal protective in an Alport syndrome mouse model and type 2 diabetes patients. Here, we investigated whether MES+HS promotes the recovery from AKI and suppresses the AKI to CKD transition. Methods: We used a mouse model of bilateral ischemia-reperfusion injury (Bi-IRI) to investigate the effects of MES+HS on renal pathologies associated with AKI. The mice were treated with MES (55 pps, 12 V) + HS (42 °C) for 10 minutes twice a week from day 1 to day 14 after Bi-IRI. Results: The renal function of the Bi-IRI mouse model rapidly decreased and then recovered over time by day 14 after Bi-IRI. However, tubular damage, inflammation, and fibrosis were observed even after recovery of renal function on day 14 after Bi-IRI. MES+HS promoted the recovery of renal function in these mice. Moreover, MES+HS significantly suppressed tubular damage, inflammation, and fibrosis on day 14 after Bi-IRI. Expression of oxidative stress markers was significantly reduced by MES+HS after 7 days of treatment. It has been reported that a subpopulation of failed-repair proximal tubular cells (FR-PTC) emerges after AKI and is involved in the development of chronic disorders. We found that MES+HS reduced the number of Vcam1-positive tubular cells, a marker of FR-PTC, suggesting that MES+HS promotes normal tubular repair. Conclusion: MES+HS can suppress AKI to CKD transition by modulating inflammation, fibrosis, oxidative stress and the emergence of FR-PTC.