A High-Throughput AngioPlate Platform with Integrated AngioTEER for Modeling and Monitoring Renal Proximal Tubule Injury

Renal tubular injury is the leading cause of acute and chronic kidney diseases. This condition occurs when renal proximal tubular epithelial cells sustain damage from exposure to nephrotoxins, infections, or ischemia leading to tubular interstitial fibrosis and eventually organ failure. Despite its severity, the pathophysiology of several renal tubular injuries remains inadequately understood with no treatment due to lack of predictive preclinical models. Here a model of renal proximal tubules is reported on an AngioPlate platform integrated with Trans Electrical Epithelial Resistance measurements (AngioTEER) for automated, real-time monitoring of tubular barrier integrity in 128 tissues in health and in response to injury. The platform is used to successfully model drug and hypoxia-induced tubular injuries. In addition, the platform's use of amenable extracellular matrices is leveraged to model renal fibrosis by co-culturing fibroblasts with renal proximal tubules. Given the lack of approved treatments for tubulointerstitial fibrosis, the possibility of repurposing pirfenidone is explored, a drug currently approved for lung fibrosis, and found that it may offer a potential therapeutic effect for this challenging condition. Overall, this work demonstrates the versatility of our engineered 3D renal proximal tubule model to study renal disease mechanisms and screen potential treatment options.