Researchers from the Korea Advanced Institute of Science and Technology (KAIST) have developed an advanced organ-on-a-chip system that makes it possible to study, in real time, how drug-induced muscle damage can lead to acute kidney injury. The technology offers a new, human-relevant way to investigate complex inter-organ interactions that until now have been difficult to observe directly.
Rhabdomyolysi, a condition in which muscle breakdown releases toxic substances into the bloodstream, is a known but poorly understood cause of acute kidney failure. While certain medications are known to trigger this cascade, traditional laboratory models have been unable to simultaneously capture the dynamic relationship between muscle and kidney tissue.
Human-like modular lab model
The newly developed platform changes that. Led by Professor Seongyun Jeon (Mechanical Engineering, KAIST), in collaboration with Professor Gi-Dong Sim and clinicians from Seoul National University Hospital, the research team designed a modular biomicrofluidic organ-on-a-chip system that closely mimics human physiology. The study was published in Advanced Functional Materials.
The system integrates three-dimensionally engineered muscle tissue with kidney proximal tubule epithelial cells on a single microfluidic chip. Its modular design allows the two tissue types to be cultured separately under optimal conditions, then temporarily connected to enable controlled inter-organ communication. After experimentation, the tissues can be disconnected again for independent, detailed analysis. This approach enables researchers to quantitatively assess how toxic substances released by damaged muscle tissue affect kidney function. This is something that has not been possible with conventional in vitro or animal models.
Reproducing drug-induced injury pathways
To validate the platform, the researchers tested two widely used lipid-lowering drugs, atorvastatin and fenofibrate, both known to carry a risk of muscle toxicity. On the chip, exposure to these drugs caused muscle tissue to lose contractile strength and structural integrity, while releasing biomarkers such as myoglobin and CK-MM that are characteristic of rhabdomyolysis.
Crucially, these changes were followed by progressive damage to the connected kidney tissue. The researchers observed reduced cell viability, increased cell death, and elevated levels of NGAL and KIM-1—key biomarkers associated with acute kidney injury. For the first time, the full step-by-step cascade from muscle injury to kidney damage could be observed and measured in a laboratory setting.
Drug development and safety
According to Professor Jeon, the platform provides a new foundation for studying organ-to-organ toxicity in a way that more closely reflects the human body. By capturing systemic effects early in development, such organ-on-a-chip technologies could help improve drug safety assessment, reduce reliance on animal models, and identify adverse effects before clinical trials. "We expect this platform to enable the early prediction of drug side effects, identification of the causes of acute kidney injury, and further expansion toward personalized drug safety assessment."
More broadly, the study highlights the growing role of microphysiological systems in precision medicine and regulatory science. As drug development increasingly demands human-relevant, data-rich models, modular organ-on-a-chip platforms like this one could become a critical tool for understanding complex toxicity mechanisms and improving patient safety.
