Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice
Abstract
Rhabdomyolysis causes severe AKI and death in settings such as earthquakes and armed conflict. Specific treatment is not available and care is difficult to provide in these austere environments. Skeletal muscle myoglobin is a renal toxin that causes AKI in this syndrome. Proximal tubular megalin participates in myoglobin endocytosis and may be an AKI mediator. The authors demonstrate in a mouse model that proximal tubular megalin plays a critical role in rhabdomyolysis-induced AKI. In this model, proximal tubule–specific megalin deletion ameliorated AKI, and this effect was recapitulated by administration of cilastatin, a megalin inhibitor. This translational study thus identifies megalin as a mediator of rhabdomyolysis-induced AKI and suggests a novel mechanism by which it may be possible to ameliorate this condition.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2021
- Source ID
- 10.1681/asn.2020030263
Entities
People
- Adam C. Munhall
- James A. McCormick
- Jessica F Hebert
- Katsuyuki Matsushita
- Kiyoshi Mori
- Mahaba B. Eiwaz
- Megan N. Nickerson
- Michael P. Hutchens
- Motoko Yanagita
- Turgay Saritas
- Yoshio Funahashi
Organizations
- Japan Agency for Medical Research and Development
- Kyoto University
- National Institute of Diabetes and Digestive and Kidney Diseases
- Oregon Health & Science University
- RWTH Aachen University
- United States Department of Defense
- United States Department of Veterans Affairs
- University of Shizuoka
- Veterans Affairs Medical Center (Oregon)