Researchers from University of Michigan have devised a device, dubbed “kidney on a chip,” that imitates the flow of drugs through human kidneys, and also measures its effect on kidney cells. It has shown potential to improve medication dosing in intensive care units.
With almost two-thirds of patients in ICUs experiencing serious kidney injury, and medications blamed in more than 20 percent of these cases, this treatment has the potential benefit of providing more precise dosing of potentially toxic medicines.
Researchers have long relied on animal testing to measure the toxicity of drugs and to determine safe doses, but because animals process drugs more rapidly than humans, this technique can inadvertently lead them to underestimate a drug’s toxicity, according to the Michigan team.
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So, how does the “kidney on a chip” work? The technique utilizes a microfluidic chip device to deliver a precise flow of medication across cultured kidney cells.
The Michigan researchers, whose work was published in the journal Biofabrication, compared two different dosing regimens for gentamicin, an antibiotic that’s commonly used in ICUs. They developed a microfluidic device that sandwiches a thin, permeable polyester membrane and a layer of cultured kidney cells between the top and bottom compartments.
They pumped gentamicin solution into the top compartment, where the antibiotic gradually filtered through the cells and the membrane, simulating the flow of medication through a human kidney.
One test began with a high concentration that quickly tapered off, mimicking a once-daily drug dose. The second test simulated a slow infusion of the drug, using a lower concentration that remained constant.
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They then measured damage to the kidney cells inside the device and found that a once-daily dose is significantly less harmful than a continuous infusion—even though both cases ultimately delivered the same amount of medication.
“The most significant impact of the research is providing a better understanding of how to safely administer drugs,” said Shuichi Takayama, professor of biomedical engineering at the University of Michigan.
“This type of study was something that could not be done well in animals because drug clearance is much faster than in humans. Existing human clinical data has been inconclusive for this particular drug and is too expensive to collect new data specifically for this drug,” Takayama said.
Photo: Joseph Xu, Michigan Engineering Communications & Marketing