The application of shear wave quantitative ultrasound elastography in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem, so it is particularly important to quantitatively assess and intervene in the degree of early renal damage in CKD. OBJECTIVE: The objective of the research is to establish reference values for kidney elasticity by using real-time shear wave elastography (RT-SWE) technology to quantify Young's modulus values in the renal cortex of normal adults. The intention is to provide a foundation for evaluating renal function and structural changes in patients with CKD. Furthermore, this research investigates the role of RT-SWE in the early detection of renal fibrosis in CKD, providing insights into its diagnostic value for detecting pathological changes at an early stage. METHODS: Between August 2019 and December 2021, we collected a sample of 100 healthy people (55 men with an average age of 43.5 ± 15.2 years and 45 women with an average age of 41.6 ± 19.8 years) for medical evaluations at our hospital's Department of Ultrasound Medicine. In addition, 97 individuals with CKD1-3 stage were considered. Following the removal of contraindications and relevant confounding variables, we included a final cohort of 80 individuals in the research (45 men and 35 females, with an average age of 39.1 ± 19.2 years). The RENAL mode was selected and a convex array probe S6-1 operating at a frequency of 3.5-5.5 MHz was used in the research, which made use of the French Supersonic AixPlorer ultrasonic diagnostic instrument. Renal RT-SWE elastography was performed after conventional two-dimensional and color Doppler ultrasonography. The study used RT-SWE technology to assess the mean Young's modulus of the cortex in healthy individuals (Emean), with data analysis and comparisons based on age and gender. Furthermore, the Emean values of CKD stage 1-3 patients were determined, and analyses were performed about 24-hour urine protein quantitative (24hUTP), serum creatinine concentration (SCr), and renal biopsy pathology, specifically the degree of interstitial fibrosis. RESULTS: Healthy group: a) The average kPa values of the left kidney (4.2 ± 2.3), right kidney (4.3 + 2.5) kPa, both kidneys' average kPa values (4.3 ± 2.4) kPa, and the average kPa values of the left and right kidneys do not differ statistically (p= 0.986). b) There was no difference in the kPa values of healthy male and female kidneys (4.4 + 2.1 and 4.2 + 2.6, respectively. c) There was no difference in the renal kPa values of healthy adults aged 50 (4.4 ± 2.8) kPa and renal kPa of the 50-year-old population (4.2 + 2.1) kPa (p= 0.041). Case group: a) the group of patients with CKD1-3 stage and the group did not vary in their Emean values (both p< 0.05); b) There is a difference between CKD stages 1, 2, and 3 (p< 0.05), however, there is still no difference in the pyEmean value corrected for patient age between patients in stages 1 and 2 (p> 0.05). CONCLUSION: The study reveals no significant differences in the Emean value of bilateral kidneys in normal people and no differences in the elasticity value of kidneys and gender. However, age-based differences were statistically significant. pyEmean may be useful for comparing CKD stage 1, 2, and 3 patients, and RT-SWE can assess early renal damage.

Enhancement of Tumor Perfusion and Antiangiogenic Therapy in Murine Models of Clear Cell Renal Cell Carcinoma Using Ultrasound-Stimulated Microbubbles.

OBJECTIVE: To explore the effect of ultrasound-stimulated microbubble cavitation (USMC) on enhancing antiangiogenic therapy in clear cell renal cell carcinoma. MATERIALS AND METHODS: We explored the effects of USMC with different mechanical indices (MIs) on tumor perfusion, 36 786-O tumor-bearing nude mice were randomly assigned into four groups: (i) control group, (ii) USMC0.25 group (MI = 0.25), (iii) USMC1.4 group (MI = 1.4) (iv) US1.4 group (MI = 1.4). Tumor perfusion was assessed by contrast-enhanced ultrasound (CEUS) before the USMC treatment and 30 min, 4h and 6h after the USMC treatment, respectively. Then we evaluated vascular normalization(VN) induced by low-MI (0.25) USMC treatment, 12 tumor-bearing nude mice were randomly divided into two groups: (i) control group (ii) USMC0.25 group. USMC treatment was performed, and tumor microvascular imaging and blood perfusion were analyzed by MicroFlow imaging (MFI) and CEUS 30 min after each treatment. In combination therapy, a total of 144 tumor-bearing nude mice were randomly assigned to six groups (n = 24): (i) control group, (ii) USMC1.4 group, (iii) USMC0.25 group, (iv) bevacizumab(BEV) group, (v) USMC1.4 +BEV group, (vi) USMC0.25 +BEV group. BEV was injected on the 6th, 10th, 14th, and 18th d after the tumors were inoculated, while USMC treatment was performed 24 h before and after every BEV administration. We examined the effects of the combination therapy through a series of experiments. RESULTS: Tumor blood perfusion enhanced by USMC with low MI (0.25)could last for more than 6h, inducing tumor VN and promoting drug delivery. Compared with other groups, USMC0.25+BEV combination therapy had the strongest inhibition on tumor growth, led to the longest survival time of the mice. CONCLUSION: The optimized USMC is a promising therapeutic approach that can be combined with antiangiogenic therapy to combat tumor progression.

A novel NSUN5/ENO3 pathway promotes the Warburg effect and cell growth in clear cell renal cell carcinoma by 5-methylcytosine-stabilized ENO3 mRNA.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) cells often reprogram their metabolisms. Enolase 3 (ENO3) is closely related to the Warburg effect observed in cells during tumor progression. However, the expression and function of ENO3 in ccRCC cells remain unclear. Therefore, this study investigated the expression and functional significance of ENO3 in the Warburg effect observed in ccRCC cells. METHODS: In this study, B-mode and microflow imaging ultrasound examinations were performed to evaluate patients with ccRCC. The extracellular acidification rate test and glucose uptake and lactate production assays were used to examine the Warburg effect in ccRCC cells. Western blotting, quantitative reverse transcription polymerase chain reaction, and immunochemistry were used to detect the expression of ENO3 and NOP2/Sun RNA methyltransferase 5 (NSUN5). RESULTS: ENO3 upregulation in ccRCC tumor tissues was accompanied by an increase in tumor size. Importantly, ENO3 participated in the Warburg effect observed in ccRCC cells, and high levels of ENO3 indicated a poor prognosis for patients. Loss of ENO3 reduced glucose uptake, lactate production, and extracellular acidification rate as well as inhibited ccRCC cell proliferation. Furthermore, NSUN5 was involved in the ENO3-regulated Warburg effect and ccRCC cell progression. Mechanically, NSUN5 was upregulated in ccRCC tissues, and NSUN5 upregulation mediated 5-methylcytosine modification of messenger RNA (mRNA) in ccRCC cells to promote mRNA stability and ENO3 expression. CONCLUSIONS: Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.