Correct drug dosage delivered through a "kidney on a chip" helps prevent kidney damage, a new research has found.
The kidneys act like toxic collectors in the body as they process 120 to 150 quarts of blood to excrete toxins out of the body. Part of what is filtrated includes medications, and when it gets bombarded with several drugs over a period of time, the kidneys become stressed and undergo failure.
One study has even found long-term use of proton pump inhibitors can cause kidney failure and other kidney related diseases.
Now, researchers from University of Michigan were able to develop a kidney on a chip that imitates how human kidneys process medications while measuring their effects on kidney cells.
Accurate dosing is necessary, particularly in patients confined in the intensive care unit because their kidneys are compromised already, but to achieve it can be challenging. Most of medication dosing is based on animal studies that measure drug toxicity and safe dosages. Animals, however, process these medications more rapidly than humans and this often leads to underestimation of drug toxicity.
With the newly developed technique, researchers said, will help identify safe dosages in humans because the device can closely mimic the environment of a human kidney.
Researchers said that what they developed is the first of its kind to study the pharmacokinetic profile of a drug in the body. Professor of Biomedical Engineering at University of Michigan Shuichi Takayama said once drug is administered, it undergoes rapid concentration uptake before gradually filtered out in the kidneys. This process, Takayama said, was mimicked by the kidney on a chip.
For their study, researchers used a microfluid chip device to deliver accurate flow of drugs to cultured kidney cells, where they were able to replicate the different functions of kidneys. The researchers placed cultured kidney cells and a permeable polyester membrane in between the microfluidic device's top and bottom compartments.
Gentamicin was pumped on the top compartment where it was noted to mimic the gradual flow of drugs in the human cells and membranes. The researchers compared two different gentamicin regimens: a once-daily dose with high initial concentration and rapid reductions and a slow infusion therapy where drugs are given in constant low doses over a period of time.
Seoul National University Bundang Hospital associate professor and former University of Michigan researcher Sejoong Kim said they were able to observe that the manner of drug administration produces different effects on the body regardless of whether or not it is the same dosage of the same drug. They found that giving daily doses are less likely to harm the kidneys than the slow and continuous infusion, even if they have the same dosage.
Takayama hopes that future studies would develop their techniques to cover more organs and different types of medications. This way, drug dosing can be fine-tuned depending on what patients should only have in their body.
"We were able to get results that better relate to human physiology, at least in terms of dosing, than what's currently possible to obtain from common animal tests," said Takayama. "The goal for the future is to improve these devices to the point where we're able to see exactly how a medication affects the body from moment to moment, in real time.
The study was published in Biofabrication on March 24.
