Does empagliflozin intervention have a protective effect in the rhabdomyolysis model? Analysis of functional parameters and renal structures.

Abstract

Rhabdomyolysis (RB) is characterized by rapid injury to the striated muscle with rupture and/or necrosis of muscle fibers, associated with trauma events. Such rupture results in the release of nephrotoxic products into the bloodstream that obstruct the proximal convoluted tubules, causing a sudden decline in renal function and, consequently, leading to acute kidney injury (AKI). However, despite the knowledge of its pathophysiology, treatments for RB are still incipient. Recent evidence has suggested that empagliflozin, a sodium-glucose-2 co-transporter (iSGLT2) inhibitor, has a protective factor for microalbuminuria, reducing the progression of chronic kidney disease (CKD) as well as improving mitochondrial biogenesis, increasing angiogenesis and important parameters for the resumption of renal function (reduction of creatine and urea, indicating an improvement in the glomerular filtration rate). However, these results come from cardiovascular studies, and studies focusing on AKI are needed. Thus, the objective of this project is to study the feasibility of iSGLT2 in accelerating the recovery of kidney tissue after the RB process or even mitigating the effects of kidney injury. To do so, we will use the following approaches: quantify the pool of renal c-Kit+ cells, to visualize the recovery power of renal tissue after the insult; to evaluate the CPK, NGAL, KIM-1, BUN and creatinine markers, allowing us to assess the renal function of our animal model; and, finally, we will proceed with the evaluation of mRNA, protein necroptosis markers (RIP1-RIP3-MKL), oxidative stress (4-HNE) in order to elucidate tissue stress processes in a global way. From such procedures, the aim is to verify the safety and efficacy of the intervention for the adoption of a future treatment for rhabdomyolysis and AKI.