Kidney Organoids May Speed AKI Drug Screening, With Alexander Combes, PhD

Acute kidney injury (AKI) management remains limited to supportive care, and no pharmacologic therapy is approved specifically to prevent injury or accelerate recovery after an ischaemic insult in clinical practice. Biopsy studies increasingly implicate specific cellular and molecular pathways in AKI and its progression to chronic kidney disease (CKD), but testing which pathways actually drive injury or recovery requires a controllable human system. Animal models remain essential but are difficult to scale for drug screening, and species differences limit direct translation of findings to human AKI biology.

Alexander Combes, PhD, head of the Development and Disease Laboratory at Monash Biomedicine Discovery Institute, led a human kidney organoid model of ischaemic AKI, published August 19, 2026, in Genome Medicine.¹ The model identified cellular, molecular, and metabolic signatures of AKI and persistent post-injury states, providing targets investigators can test experimentally rather than relying only on biopsy correlations across acute and chronic timepoints. Combes' lab is also developing a higher throughput organoid format designed for multiwell drug screening, aiming to identify candidates able to protect kidney tissue or improve recovery after injury.

For nephrologists, the approach offers a route to prioritize candidate therapies before animal testing, screening both approved drugs for repurposing and compound libraries with defined mechanisms of action, potentially shortening the path to clinical testing. "Our goal is to use these models to find treatments that could protect the kidney or improve recovery after injury," Combes said in a statement.² Combes spoke with HCPLive about how the platform could be used to screen and repurpose therapies for AKI.

Q&A: Using Kidney Organoids to Screen AKI Therapies

HCPLive: Does this research move the needle on AKI's lack of targeted therapies?

Alexander Combes, PhD: Clinical biopsy studies are increasingly identifying the cellular and molecular pathways associated with AKI and persistent kidney injury, but we need human experimental models in which we can test which of those pathways actually drive injury or recovery. Animal models remain essential, but they are difficult to use for large-scale screening and there can be important species differences. In this study, we used a suite of profiling technologies to identify which cellular, molecular and metabolic signatures of AKI and persistent injury are reproduced in human kidney organoids. That gives us a platform where we can now target those processes experimentally and test potential therapies. My lab is also developing new ways to produce kidney organoids that are much better suited to high-throughput screening. Together, this puts us in a strong position to identify and prioritise candidate therapies for further testing in animal models and, ultimately, clinical studies.

HCPLive: What would you want a practicing nephrologist to take away from this work?

Alexander Combes, PhD: The main message is that kidney organoids reproduce important aspects of human AKI biology, including persistent injury-associated epithelial states linked to the transition from AKI to chronic kidney disease. They don't capture the functional changes or systemic context of AKI, and there are challenges in modelling adult injury in developmentally immature kidney tissue. However, the core injury and repair responses are sufficiently conserved to provide a meaningful human model for mechanistic and therapeutic studies. By combining organoids with what we are learning from patient biopsies and biomarkers, we can begin to test the mechanisms driving acute injury and incomplete recovery in a human system. We think this can improve our understanding of injury biology in both adult and neonatal AKI and provide a platform for therapeutic development.

HCPLive: What would the process of screening approved drugs for repurposing look like from here?

Alexander Combes, PhD: We're developing a higher-throughput version of the organoid model that allows us to generate kidney tissue reproducibly in multiwell formats. We can then expose these organoids to a defined injury and screen for protective therapies by looking for reductions in acute tubular injury markers, or for therapies that enhance repair by assessing persistent injury and inflammatory markers after recovery. We plan to screen both approved drugs and broader libraries of compounds with known mechanisms of action. The latter can help identify new pathways that control injury and repair, while repurposing approved drugs offers a potentially faster route to clinical translation. If we find a strong effect with a drug that already has established safety, dosing and pharmacology in patients, there may be fewer barriers to testing it for AKI than developing an entirely new drug. Promising candidates would still require rigorous validation in more complex models and ultimately clinical trials.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Nunez-Nescolarde AB, et al. Modelling ischaemic AKI in human kidney organoids reveals injury-associated epithelial states and macrophage-epithelial crosstalk. Genome Med. 2026;doi:10.1186/s13073-026-01712-z

2. Monash University. Miniature kidneys could accelerate new treatments for acute kidney injury. News release. August 20, 2026. Accessed September 8, 2026. https://www.eurekalert.org/news-releases/1140789