Kidney Week

Abstract: PUB027

Urinary Proteomics Reveals Early Injury-Associated Signatures in Mouse Rhabdomyolysis-Associated AKI

Session Information

• Publication Only

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Kukida, Masayoshi, Ehime Daigaku Igakubu Fuzoku Byoin, Toon, Ehime Prefecture, Japan

Masayoshi Kukida, MD, PhD

• Kondo, Fumikazu, Ehime Daigaku Igakubu Fuzoku Byoin, Toon, Ehime Prefecture, Japan

Fumikazu Kondo, MD

• Shichijo, Satoru, Ehime Daigaku Igakubu Fuzoku Byoin, Toon, Ehime Prefecture, Japan

Satoru Shichijo, MD

• Sakaue, Tomohisa, Ehime Daigaku Igakubu Fuzoku Byoin, Toon, Ehime Prefecture, Japan

Tomohisa Sakaue, PhD

• Sugiyama, Naoyuki, Kokuritsu Junkankibyo Kenkyu Center, Suita, Osaka Prefecture, Japan

Naoyuki Sugiyama, PhD

• Yamaguchi, Osamu, Ehime Daigaku Igakubu Fuzoku Byoin, Toon, Ehime Prefecture, Japan

Osamu Yamaguchi, MD, PhD

Background

Urinary proteomics is increasingly used to characterize acute kidney injury (AKI), but urinary protein changes can reflect multiple processes. In rhabdomyolysis-associated AKI, muscle-derived protein filtration and tubular injury occur simultaneously, making it difficult to interpret urinary proteomic findings simply as injury-derived protein leakage. We examined early urinary proteomic changes in a wild-type mouse model of rhabdomyolysis-associated AKI.

Methods

Rhabdomyolysis-associated AKI was induced in <!--StartFragment -->8–10-week-old male C57BL/6J mice. Urine samples were collected before induction and 24 hours after induction. Kidney injury was confirmed by blood chemistry and histological assessment. Urinary proteins were analyzed by using data-independent acquisition mass spectrometry (n=3), and differentially abundant proteins were classified according to known functions and related pathways.

Results

At 24 hours after rhabdomyolysis induction, mice showed biochemical kidney dysfunction and histological tubular injury. Urinary proteomic profiles were clearly altered compared with baseline. Using an FDR threshold of <0.05, 1,333 proteins were increased and 124 proteins were decreased. Increased proteins included muscle-derived proteins such as myoglobin and creatine kinase, tubular injury-associated proteins such as NGAL and KIM-1/HAVCR1, complement-related proteins, proteins related to protease regulation and coagulation, and proteins related to intracellular protein processing and stress responses.

Conclusion

In mouse rhabdomyolysis-associated AKI, urinary proteomics captured a distinct early injury-associated protein signature. These changes were not limited to myoglobinuria, but reflected tubular injury, inflammatory and complement responses, protease regulation, and intracellular protein-processing/stress responses. Because urinary proteins may reflect both filtered muscle-derived proteins and tubular responses, further studies are needed to determine how proximal tubular protein handling contributes to these urinary signatures and how these signatures relate to tubular injury.