# Role of Shear Stress on Renal Proximal Tubular Cells for Nephrotoxicity Assays

Authors: Holly H. Birdsall; Timothy G. Hammond
Journal: Journal of Toxicology
 (2021)

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## Abstract

Drug-induced nephrotoxicity causes huge morbidity and mortality at massive financial cost. The greatest burden of drug-induced acute kidney injury falls on the proximal tubular cells. To maintain their structure and function, renal proximal tubular cells need the shear stress from tubular fluid flow. Diverse techniques to reintroduce shear stress have been studied in a variety of proximal tubular like cell culture models. These studies often have limited replicates because of the huge cost of equipment and do not report all relevant parameters to allow reproduction and comparison of studies between labs. This review codifies the techniques used to reintroduce shear stress, the cell lines utilized, and the biological outcomes reported. Further, we propose a set of interventions to enhance future cell biology understanding of nephrotoxicity using cell culture models.


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## Body

## 1. Conclusions

We propose three strategies to move the field towards a uniform model to test nephrotoxicity of drugs.First, in 2010, we proposed a minimum data set to be reported to allow reproduction of suspension culture studies in other labs [20]. As the meeting where the proposal was presented was in Bonn, we termed these the Bonn criteria [20]. They include the vessel diameter, rotation speed, media viscosity, media density, cell/organoid/spheroid diameter, and density. The Bonn criteria remain critical to interpret data between labs and allow accurate experimental reproduction between labs.Second, if different labs continue to use different techniques and reagents including cell types, some tradeoff or bake-off studies will be indispensable to understand differences between approaches.Last, the development of a low capital, inexpensive, to-use suspension culture technology would allow far more labs access to the technology and occasion the opportunity for studies to include more replicates and conditions cost-effectively.The search for a uniform model to study nephrotoxicity is severely limited by the use of a multiplicity of methods and techniques, which cannot be simply compared. Laboratories use different cell types approximating renal proximal tubular cells and apply diverse shear stress methods, and there is no systematic and adequate reporting of culture parameters. The morbidity, mortality, and cost of drug induced acute renal injury should make an integrated cell biology approach to nephrotoxicity an urgent priority.



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*Source: 6643324-2021-04-22.xml*