In vitro 3D kidney models for predicting nephrotoxicity. (A) Renal spheroids are often considered as RPTEC embedded in hydrogel to form hollow spherical cysts with an apical membrane facing the renal tubular lumen. (B) Organoids consist of multiple cells, different types of renal tubular, endothelial, and interstitial cells that self-organize in response to developmental cues and overcome the cellular simplicity of 2D cultures. (C) Three-dimensional (3D)-engineered kidney tissue consists of various renal cells with ECM as a complex and highly charged network (i.e., collagen, elastin, laminin, and glycoproteins), providing a 3D structure for the spatial organization of cells. (D) A kidney-liver-on-a-chip that comprises a perfusable, convoluted 3D renal tubule, and liver cells within the ECM enable fluid flow and the administration of test compounds to the apical surface of the cells.