Kidney Week

Abstract: SA-PO581

Efficacy of Low-Intensity Pulsed Ultrasound on Renal Fibrosis and Progression of CKD in a Mouse Model

Session Information

• Glomerular Diseases: Fibrosis, Extracellular Matrix
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1601 Pathology and Lab Medicine: Basic

Authors

• Chiang, Chih-Kang, Institute of Toxicology, School of Medicine, National Taiwan University, Taipei, Taiwan

Chih-Kang Chiang,

• Liu, Shing-Hwa, Institute of Toxicology, School of Medicine, National Taiwan University, Taipei, Taiwan

Shing-Hwa Liu,

• Hung, Kuan-Yu, National Taiwan University, Medical College, Taipei, Taiwan

Kuan-Yu Hung,

Background

The prevalence of chronic kidney disease (CKD) has been increasing in recent years. Proliferation of fibroblasts and excessive deposition of extracellular matrix including collagen in renal tissues after ischemia/reperfusion injury (IRI) contribute to renal fibrosis and progression of CKD. Low intensity pulsed ultrasound (LIPUS) has been recognized to elevate bone fracture repair process and help in some soft tissues healing such as cartilage and cardiac tissues. Here, we tested the prevention of renal fibrosis and progression of CKD by LIPUS in a mouse model of unilateral IRI with contralateral nephrectomy.

Methods

Animals were randomized into the sham, IRI, and IRI+LIPUS groups. In the IRI group, the left renal artery was isolated and clamped fir 30 mins. They were sacrificed 14 days after IRI as an AKI to CKD transition model in the presence or absence of LIPUS treatment (3 MHz, intensity 0.1 W/cm², 20 min, 50% duty factor) 5 days before and 14 days after IRI. Serum biochemical measurement, including BUN, Cr and Cystatin C, Histological analysis, Immunoblotting, including GRP78, Chop, Bax, cleaved caspase-3, p21, Sirtuin-1, E-cadherin, vimentin, catalase, superoxide dismutase 1 (SOD1), Klotho, etc.., and Malondialdehyde (MDA) were examined

Results

LIPUS treatment significantly alleviated the increases in the serum levels of BUN, creatinine, and fibroblast growth factor (FGF)-23, and renal pathological changes and fibrosis (n=8, p<0.05). The development of epithelial-mesenchymal transition was alleviated by LIPUS treatment (n=8, p<0.05). LIPUS treatment could also inhibit the induction of renal senescence-related molecular signals such as p53, p21, and p16 (n=8, p<0.05). Interestingly, LIPUS significantly reversed the decreased α-Klotho protein expression in the kidneys (n=8, p<0.05). LIPUS treatment significantly reversed the decrease in renal endogenous antioxidant enzymes (n=8, p<0.05). Taken together, LIPUS treatment showed the benefits for renal protection in IRI mice.

Conclusion

These findings suggest that LIPUS therapy may be used to serve as an auxiliary tool for the management of renal fibrosis and progression of CKD.

Funding

• Government Support - Non-U.S.