Developing a Novel Therapy for Rhabdomyolysis
Abstract
Purpose: The purpose of this project is to determine the optimal dose and timing of cilastatin therapy to determine strategies to mitigate Acute Kidney Injury (AKI) and to determine whether or not the pragmatic administration of cilastatin prevents rhabdomyolysis induced AKI (rhAKI), hyperkalemia, and mortality caused by a combat-relevant model of severe musculoskeletal trauma. Scope: To determine the optimal dose and timing of cilastatin administration and strategies to mitigate rhAKI, we will use the glycerol injection mouse model of rhabdomyolysis to determine the dose response relationship and assess cilastatins protective effect. We will test glomerular filtration rate (GFR) as the primary outcome of renal function in addition to rigorous documentation of rhabdomyolysis severity, renal inflammation, and renal histologic injury. Major Findings: Inducible proximal tubule-specific deletion of megalin is highly protective in a mouse model of induced rhAKI. Findings indicate that urine output and glomerular filtration rate were not altered by cilastatin administration. Further, cilastatin dependent protection from rhabdomyolysis-induced AKI is absent in mice without proximal tubule megalin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1149797
Entities
People
- Michael P. Hutchens
Organizations
- Oregon Health & Science University