Many lifesaving drugs can be dangerously toxic to the kidneys. Because there are a number of factors that change the way kidneys process drugs, it is very difficult to predict how they will affect each patient. Researchers from the University of Michigan have developed a “kidney-on-a-chip” that promises to make testing the effects of drugs on the kidney quicker and more reliable.
The kidneys are a pair of organs that play a number of vital roles in the human body. Their functions include waste management, regulating fluids, and balancing minerals.
They help orchestrate the production of red blood cells and, every 30 minutes, the kidneys filter the body’s entire volume of blood.
Damage to an organ with so many important functions is a serious medical issue; any new technology that might help protect the kidneys has the potential to be a lifesaver.
Up to two-thirds of patients in the intensive care unit (ICU) experience some level of kidney damage, and 20 percent of these kidney damage cases are due to drug toxicity.
Groundbreaking technology could help reduce drug-induced kidney problems. Credit: www.shutterstock.com
There are a wide range of reasons for this drug damage, but they are notoriously difficult to predict.
Kidney toxicity in the ICU
Kidneys respond to drugs differently depending on a number of factors, including the age of the patient, current medications, and other diseases that they might have. Because of this, determining what drug dosage to use can be challenging.
Animal models are used to help predict how the kidneys will react, but, because animals tend to process drugs quicker than humans, it is difficult to translate the findings to human patients.
Individuals being cared for in the ICU are particularly at risk of damage to the kidneys. This is because they are more likely to already be on other medications or have additional medical conditions. Additionally, ICU patients often undergo multiple treatments at once, making predictions even more difficult.
A research team, led by Prof. Shuichi Takayama, has designed a microfluidic chip device that mimics the way in which drugs are removed by the kidneys.
The device consists of a permeable polyester membrane and a layer of cultured human kidney cells sandwiched between an upper and lower compartment.
By closely mimicking the internal environment of the kidney, the team hopes that the device will become a reliable way of testing medications on the kidney.
“When you administer a drug, its concentration goes up quickly and it’s gradually filtered out as it flows through the kidneys. A kidney-on-a-chip enables us to simulate that filtering process, providing a much more accurate way to study how medications behave in the body.”
Prof. Shuichi Takayama
Testing the kidney-on-a-chip
To test the groundbreaking kidney-on-a-chip, the team used a common antibiotic – gentamicin. The drug was pumped into the top compartment and released into the membrane and kidney cells.
Using the mini kidney model, the team tested two different methods of drug infusion to gauge any differences in their effect on the kidney.
The first trial used a high concentration that rapidly tailed off, mimicking a patient being given a once-daily drug. Secondly, they used a lower concentration over a longer duration, mimicking a slow infusion of the drug.
Next, the researchers removed the kidney cells from the chip and tested them for damage. The results showed that the once-daily infusion was significantly less harmful to the kidneys than the continuous infusion, despite both delivering the same total volume of the drug.
“Even the same dose of the same drug can have very different effects on the kidneys and other organs, depending on how it’s administered. This device provides a uniform, inexpensive way to capture data that more accurately reflects actual human patients.”
Asst. Prof. Sejoong Kim
Looking to the future, Takayama hopes that the device can be taken “to the point where we’re able to see exactly how a medication affects the body from moment to moment, in real time.”
If the device proves successful, it has the potential to significantly reduce drug-related kidney damage in the ICU and elsewhere.
Credit: Tim Newman, http://www.medicalnewstoday.com/articles/310016.php
Picture Credit: http://img.medicalxpress.com/newman/gfx/news/hires/2013/2-harvardswyss.jpg