Renal interstitial permeability changes induced by microbubble-enhanced diagnostic ultrasound

Area of Science:

• Nephrology
• Biomedical Engineering
• Pharmacology

Background:

• Ultrasound-targeted microbubble destruction (UTMD) is explored for enhancing glomerular permeability for drug delivery in kidney diseases.
• The impact of UTMD on renal interstitial permeability remains less understood.

Purpose of the Study:

• To investigate the effect of UTMD on renal interstitial permeability.
• To evaluate the safety and reversibility of UTMD-induced permeability changes in the kidney.

Main Methods:

• Diagnostic ultrasound (DUS) with microbubbles (MBs) was used to insonate the left kidney of Sprague-Dawley rats.
• Renal vascular permeability was assessed using Evans blue (EB) dye.
• Kidney tissue was examined using hematoxylin and eosin (HE) staining and electron microscopy.
• Localization and retention of fluorescently labeled MBs were tracked.
• Urinalysis was performed to detect proteinuria.

Main Results:

• Both continuous and intermittent UTMD modes increased renal vascular permeability, which recovered within 24 hours.
• Intermittent UTMD caused more significant injury than continuous mode.
• Red blood cells leaked into the interstitium, but glomerular capillary hemorrhage was absent.
• Electron microscopy confirmed reversible disruption of interstitial capillary walls.
• Fluorescent MBs localized primarily in the renal interstitium and were retained for 24 hours.
• No clinical proteinuria was observed post-treatment.

Conclusions:

• Microbubble plus diagnostic ultrasound specifically and reversibly enhances renal interstitial permeability.
• This approach does not affect the glomerulus, suggesting potential for targeted drug delivery to specific kidney compartments.
• UTMD offers a potential therapeutic strategy for localized drug delivery in treating kidney diseases.