Table 2.

In vitro 2D vs. 3D renal models of drug-induced nephrotoxicity.

Models	Advantages	Disadvantages
2D culture	-Robust model -Easy to assess, manipulate -Cost- and time-efficient -Large scale -Retention of key metabolic	-Static model -Dedifferentiation -Lack of in vivo-like morphologic and phenotypic characteristics -Low complexity -Little predictive -Poor physiological or clinical relevance
3D culture	-In vivo-like cell shape -More physiologic characteristics -Response to toxic insults with biomarkers found in vivo -3D paracrine and autocrine signaling; -Potential penetration gradients toward center -Cells of different stages (proliferating, hypoxic, quiescent, and necrotic) possible -More similar to in vivo expression profiles -Better predictive values to in vivo compound responses	-Cost-intensive -Simplified architecture -Can be variable -Less amenable to HTS/HCS -Hard to reach in vivo maturity -Complication in assay -Lack vasculature -May lack key cell types
Animal models	-Physiological resemblance -Well established -Physiological relevance -Complete organism -Test drug metabolism	-Species differences -Low throughput -Poor prediction -Ethical concerns -High costs

Abbreviations: 2/3D, 2/3-dimensional; HTS/HCS, high-throughput screening/high content screening.