Overview of most common organotypic kidney models. (A) The proximal tubule-on-a-chip consists of an apical luminal channel separated from a basolateral interstitial fluid channel by an ECM-coated porous membrane. Primary human proximal tubule epithelial cells line the membrane to form the renal epithelial interface. Both the luminal and interstitial channels can be perfused. The device mimics the natural tissue–tissue interface in the nephron. (B) Schematic of device layers and assembled device.138 (C) Schematic illustrating the formation of proximal tubules in the 3D lumen device. (i) Cells are isolated from human kidney cortex and (ii) expanded. (iii) Expanded cells are seed into the 3D lumen device. (iv) Image of a tubule and viability at day 28. (D) 3D projection images of the cultured proximal tubule. Staining for CD13 in B1 and B2, E-cadherin in B3 and B4, and aquaporin 1 in B5 and B6. Scale bars: Cii, 200 μM; Civ, 50 μM; D, all 20 μM148. Reproduced from ref. 148 with permission from Elsevier, copyright 2017 and ref 138 with permission of Oxford University press, copyright 2013.