Project title
低強度脈衝式超音波運用於腎臟疾病治療之作用及機轉探討
Internal ID
MOST105-2314-B002-106-MY3
Principal Investigator
Start Date
August 1, 2018
End Date
July 12, 2019
Investigators
Organizations
Partner Organizations
Therapeutic Effects and Possible Mechanisms of Low-Intensity Pulsed Ultrasound on Kidney Diseases = 低強度脈衝式超音波運用於腎臟疾病治療之作用及機轉探討
Keywords
低強度脈衝式超音波
腎絲球腎炎
急性腎損傷
慢性腎臟病
low-intensity pulsed ultrasound
glomerulonephritis
acute kidney injury
chronic kidney disease
Description
Taiwan is currently the world's highest incidence of end-stage renal disease (ESRD), as well as the world's second highest prevalence. Glomerulonephritis (GN) is still the most common cause of ESRD. GN is an immune-related inflammatory disease of glomeruli characterized by inflammatory cell infiltration, excess glomerular cell proliferation, and mesangial matrix deposition in response to phlogistic stimulation. Moreover, there are a lot of poisons or drugs through a variety of mechanisms to induce renal toxicity and cause acute kidney injury (AKI), including acute renal tubular cell injury and necrosis or acute renal interstitial nephritis. Chronic kidney disease (CKD) is a worldwide public health problem. There is an increasing incidence and prevalence of patients with kidney failure requiring replacement therapy, with poor outcomes and high cost. Tubulointerstitial fibrosis, regardless of the initial renal insults, is a common pathological presentation of CKD. The most important feature of ESRD is renal interstitial fibrosis, which is characterized by normal renal structure replaced by abnormal accumulation of extracellular matrix proteins, tubular atrophy, tubular expansion and glomerular sclerosis. The methods for ESRD treatment include hemodialysis, peritoneal dialysis, and kidney transplantation, which are costly and can only kidney transplant patients return to approximately normal renal function. On the other hand, ultrasound is widely used for diagnostic medical imaging, and is a safe and effective modality to visualize pathological lesions in human body. In recent years, ultrasound has also been found to be used as a method for treating a disease, its main application has two aspects, one is a high intensity focused ultrasound formula (HIFU), and the other is a low-intensity pulsed ultrasound (LIPUS). HIFU can lead to thermal effects style, with good penetration in human tissues, energy can be transferred to the deep tissue, the focus area can cause the temperature rises, burning causing damage to proteins or cell injury/apoptosis within tissues. Accumulation of such large energy can be applied to the thermal cautery treatment of tumor cells. However, the HIFU method using high-temperature heat treatment usually might damage the surrounding normal cells or tissues. LIPUS, as compared to HIFU, is less likely to cause harm and can be restored, so the range of applications can be more extensive, for example, LIPUS effectively alleviated bone disease. However, the therapeutic effects of LIPUS on kidney diseases are still unclear. The aims of this research project are to investigate the preventive and therapeutic effects of LIPUS on kidney diseases using cell and animal models. The results of our preliminary experiments can support the ideas of this project. This is a three-year project. First year: To investigate the preventive and therapeutic effects and possible mechanisms of LIPUS on cytokines/lipopolysaccharide-treated mesangial cell model and anti-thy-1 rat model of GN. Second year: To investigate the preventive and therapeutic effects and possible mechanisms of LIPUS on hypoxia/reperfusion-exposed renal tubule cell model and ischemia/reperfusion-exposed mouse mnodel of AKI. Third year: To investigate the preventive and therapeutic effects and possible mechanisms of LIPUS on TGF-pi-treated renal tubule cell model and unilateral ureteral obstruction (UUO) rat model of CKD. This project is a new concept. The non-invasive LIPUS, which intensity is in the range of diagnostic ultrasound, will be used to test its effects on acute and chronic renal injury. If these cell and animal model experiments can prove that this method is work for the preventive or treatment of kidney diseases, the clinical trials or even used in clinical preventive or treatment will be expected or anticipated in the future.