Microfluidics meets organoids: Kidney and bladder-on-Chip models for preclinical drug delivery assessment

High clinical attrition rates in drug development are frequently driven by unforeseen drug-induced nephrotoxicity, a challenge exacerbated by the profound interspecies differences and limited predictivity of conventional animal models. This translational gap is further compounded by the difficulty of recapitulating the complex, multilineage architecture of the human kidney and the stratified urothelial barrier of the bladder using traditional static cultures. Human induced pluripotent stem cell (hiPSC)-derived organoids integrated into microphysiological systems (MPS) offer a transformative opportunity to overcome these hurdles by merging human-specific biological complexity with precisely controlled engineering niches. In this review, we evaluate the evolution of kidney and bladder models from foundational platforms utilizing immortalized or primary cells to hiPSC-derived organoid-integrated chips, focusing on their quantitative capability to predict renal drug disposition and intravesical delivery. We detail the strategic integration of these human-relevant parameters into industrial physiologically based pharmacokinetic (PBPK) modeling and regulatory workflows. Furthermore, we highlight emerging synergies with multi-omics, computational "Digital Twins," and multidisciplinary engineering advances, including vascularization, real-time biosensing, and 3D bioprinting technologies with AI-guided automation for scalable, reproducible production. These platforms promise to transform preclinical assessment by delivering mechanistically precise, human-relevant data for de-risking therapeutics.