Abstract
AKI is considered as a "curable disease", but recent epidemiological studies and meta-analysis have revealed that AKI is a risk factor for CKD. Therefore, it is necessary to establish a treatment that can control the AKI to CKD transition. We have studied mild electrical stimulation (MES) and heat shock (HS; 42℃) that promotes effective biological responses. Interestingly, in adriamycin (ADR)-induced nephrotic syndrome (NS) mouse model, MES+HS significantly suppressed albuminuria and proteinuria, which are characteristics of NS. We also investigated the effects of MES+HS on AKI to CKD transition in a mouse model of bilateral ischemia reperfusion injury (Bi-IRI). The renal function of Bi-IRI mouse model was rapidly decreased and then recovered over time. However, tubular damage, inflammation and fibrosis were observed even after recovery of renal function. MES+HS promoted the recovery of renal function in this model. Moreover, MES+HS significantly suppressed tubular damage, inflammation, and fibrosis, which are indicators of AKI to CKD transition on day 14 after Bi-IRI. It has been reported that a subpopulation of failed-repair proximal tubular cell (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. Together, MES+HS can suppress AKI to CKD transition by regulating inflammation, fibrosis and also the emergence of FR-PTC involved in the chronicity of the renal disorder.
