@article {Ioannidis2022,
	title = {Aminoglycoside-induced lipotoxicity and its reversal in kidney on chip},
	journal = {Lab on a Chip},
	volume = {6},
	number = {6},
	year = {2022},
	note = {cited By 3},
	abstract = {Aminoglycosides are an important class of antibiotics that play a critical role in the treatment of life-threatening infections, but their use is limited by their toxicity. In fact, gentamicin causes severe nephrotoxicity in 17\% of hospitalized patients. The kidney proximal tubule is particularly vulnerable to drug-induced nephrotoxicity due to its role in drug transport. In this work, we developed a perfused vascularized model of human kidney tubuloids integrated with tissue-embedded microsensors that track the metabolic dynamics of aminoglycoside-induced renal toxicity in real time. Our model shows that gentamicin disrupts proximal tubule polarity at concentrations 20-fold below its TC50, leading to a 3.2-fold increase in glucose uptake, and reverse TCA cycle flux culminating in a 40-fold increase in lipid accumulation. Blocking glucose reabsorption using the SGLT2 inhibitor empagliflozin significantly reduced gentamicin toxicity by 10-fold. These results demonstrate the utility of sensor-integrated kidney-on-chip platforms to rapidly identify new metabolic mechanisms that may underly adverse drug reactions. The results should improve our ability to modulate the toxicity of novel aminoglycosides. {\textcopyright} 2022 The Royal Society of Chemistry.},
	doi = {10.1039/d2lc00825d},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141544098\&doi=10.1039\%2fd2lc00825d\&partnerID=40\&md5=5fd1500d95c42611af06a1bc9811c2a8},
	author = {Ioannidis, K. and Cohen, A. and Ghosheh, M. and Ehrlich, A. and Fischer, A. and Cohen, M. and Nahmias, Y.}
}
