Trajectory-resolved human kidney organoid model defines OPFR developmental toxicity linked to adult CKD

As nephrogenesis establishes nephron endowment underlying fetal-origin adult-onset CKD, we developed a scalable, nephron-enriched, and trajectory-resolved human kidney organoid model using simple suspension culture approach.

Using this model, we took organophosphate flame retardants (OPFRs), ubiquitous environmental contaminants in human embryos, as a representative class of chemical that disrupt nephrogenesis by specifically impairing the critical developmental transition underlying pre-tubular aggregation. We modeled our findings in organoids by treating pregnant mice with OPFR and followed the CKD-like phenotypes of their progeny later in adulthood.