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

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.

Figure 1

Varying conditions used to expose PTC to shear stress in vitro. The graph illustrates the varying intensity and duration of shear stress applied to cultured PTC from 25 reports in the literature. The y-axis is the intensity of shear force in dynes/cm², and the x-axis is the duration of the exposure in hours. When a report used multiple of conditions, arrows indicate the range of intensities, and/or times and the marker is placed at the average value. Each publication is indicated with a number which corresponds to the citation in Table 1. The marker shape indicates the method used to apply the fluid shear stress: blue squares are parallel plates and microfluidics, red circles are rotating wall suspension culture, and green triangles are stirring bioreactors and orbital shakers.