In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids

Abstract The bidirectional communication between the heart and kidney is essential for physiological homeostasis, with injury in one organ often impairing the other. Although cardiorenal crosstalk is clinically relevant in conditions such as cardiorenal syndrome (CRS), the underlying molecular and cellular mechanisms remain poorly understood, and in vitro models are lacking. Here, we developed a co-culture system using human induced pluripotent stem cell (hiPSC)-derived kidney organoids (kOs) and cardiac microtissues (cMTs) to model the cardiorenal axis. kOs exposed to nephrotoxic compounds for 72 h displayed glomerular and tubular damage, reduced cell viability, and altered gene expression. When subsequently co-cultured with cMTs for 72 h, injured kOs induced secondary cardiac dysfunction characterized by reduced cell viability, impaired contractility, and endothelial cell loss. These findings demonstrate that kidney injury can elicit detrimental effects on cardiac tissues in vitro. This organoid-based platform offers a valuable tool for studying cardiorenal interactions and underlines the potential of multi-organ models for investigating mechanisms of interdependent organ dysfunction.