High-throughput microfluidic spheroid technology for early detection of colistin-induced nephrotoxicity with...

Area of Science:

• Nephrology
• Pharmacology
• Biomedical Engineering

Background:

• Colistin is vital for treating multidrug-resistant Gram-negative infections.
• Colistin causes significant nephrotoxicity, posing a clinical challenge.
• Current methods for assessing colistin nephrotoxicity are limited by drug metabolism and plasma availability.

Purpose of the Study:

• To develop a novel platform for assessing colistin-induced nephrotoxicity.
• To improve the accuracy and efficiency of predicting kidney damage from colistin treatment.
• To enable personalized medicine approaches for antibiotic therapy.

Main Methods:

• Development of the Spheroid Nephrotoxicity Assessing Platform (SNAP), a microfluidic device.
• Utilizing renal proximal tubular epithelial cell (RPTEC) spheroids.
• Detection of colistin toxicity using 200 μL of patient plasma within 48 hours.

Main Results:

• SNAP demonstrated higher expression of kidney markers (AQP1, LRP2) compared to 2D cultures.
• SNAP detected colistin toxicity at 50 μg ml^-1 with superior sensitivity and no false positives from healthy donor plasma.
• Clinical validation showed 100% accuracy in identifying patients at risk of nephrotoxicity and 75% accuracy in predicting non-occurrence.

Conclusions:

• SNAP is a precise, efficient, and non-invasive tool for assessing antibiotic-induced nephrotoxicity.
• The platform holds significant potential for personalized medicine in managing resistant bacterial infections.
• SNAP enhances the safety and efficacy of colistin treatment by enabling early risk identification.