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Kidney Week

Abstract: TH-PO953

Exploring the Therapeutic Strategy of Low-Intensity Pulsed Ultrasonography in Age-Related CKD

Session Information

Category: Geriatric Nephrology

  • 1300 Geriatric Nephrology

Authors

  • Liu, Shing-Hwa, National Taiwan University, Taipei, Taiwan
  • Chiang, Chih-Kang, National Taiwan University, Taipei, Taiwan
  • Chang, Ting-Yu, National Taiwan University, Taipei, Taiwan
  • Wu, Cheng-Tien, China Medical University, Taichung, Taiwan
Background

The global population is entering an aging stage. The prevalence of chronic kidney disease (CKD) in people ≥65 years old is much higher than that of people under 65 years old. Ultrasound has been a useful diagnostic tool for a long time. Non-invasive low-intensity pulsed ultrasound (LIPUS) has been found to be a method for treating diseases, such as neurological or bone diseases. Our team's studies also found that LIPUS could effectively alleviate the renal dysfunction in AKI and CKD mouse models. The preventive or therapeutic strategies for age-related CKD still need to be clarified or developed. Here, we evaluated the interventional potential of LIPUS on CKD progression in a naturally aging mouse model.

Methods

Male C57BL/6 mice with the age of 3 (young control), 12, and 24 months (human age equivalent: about 20, 42.5, and 69 years, respectively) were tested. LIPUS with condition of 3 MHz, 0.1 W/cm2, 20 min daily was applied to the kidney of aged mice for one month. The biochemical analysis in the serum, histological examination in the kidney, and protein expression for senescence-related signaling molecules in the kidney were determined.

Results

In naturally aged mice, the serum creatinine and cystatin C, but not BUN, levels were significantly increased in mice with 24-month-old (p<0.05, n=6), but not 12-month-old (p>0.05, n=6), compared to the young control mice (3-month-old), which could be significantly reversed by LIPUS stimulation (p<0.05, n=6). The periodic acid-Schiff stain and Masson's trichrome stain showed that there were histological changes and collagen deposition, respectively, in aged mice with 24-month-old (p<0.05, n=6), which could be significantly reversed by LIPUS stimulation (p<0.05, n=6). The protein expression levels of senescence markers including senescence-associated secretory phenotype (SASP)-related signals (p53, p21, GATA-4, NFκB, TGFβ, IGFBP3, and PAI-1) increased in the kidneys of aged mice (p<0.05, n=6). LIPUS treatment significantly prevented the increased senescence signals in the kidney of aged mice (p<0.05, n=6).

Conclusion

These findings suggest that cell senescence in the kidney may contribute to the CKD progression in naturally aged mice. LIPUS is capable of inhibiting the renal cell senescence in the aging kidney and may have potential for treating age-related CKD.

Funding

  • Government Support – Non-U.S.