ATLA::Alternatives to Laboratory Animals

Volume 25, Number 5

Nephrotoxicity testing in vitro: the current situation. (ECVAM Nephrotoxicity Task Force Report 1)

ATLA 25, 497-504, September/October 1997

Jean-Paul Morin,¹ Marc E. De Broe,² Walter Pfaller³ and Gabriele Schmuck⁴

¹INSERM U295, School of Medicine-Pharmacy, University of Rouen, Avenue de l'Université, 76803 Saint Etienne du Rouoray, France; ²Department of Nephrology & Hypertension, University of Antwerp, Wilrijstraat 10, 2650 Edegem Antwerpen, Belgium; ³Institute of Physiology, University of Innsbruck, Fritz-Preglstrasse 3, 6010 Innsbruck, Austria; Department of Research Toxicology, Bayer AG, 4296 Wuppertal, Germany

SUMMARY

An ECVAM task force on nephrotoxicity has been established to advise, in particular, on the follow-up to recommendations made in the ECVAM workshop report on nephrotoxicity testing in vitro. Since this workshop was held, in 1994, there have been several improvements in the techniques used. For example, the duration of renal slice viability, and the maintenance of functional activities in slices, have been improved by using dynamic incubation systems with higher oxygen tensions and more-appropriate cell culture media. Highly differentiated primary cultures of pig, human and rabbit proximal tubule cells have been established by using specific cell isolation procedures and/or selective culture media. To date, the most comparable phenotypic expression and transepithelial transport capacities to proximal tubules in vivo have been obtained with primary cultures of rabbit proximal tubule cells which are grown on bicompartmental supports; in this system, transepithelial substrate gradients are generated and the transepithelial transport of both organic anions and cations is highly active. This in vitro system has been selected by ECVAM for further evaluation and prevalidation. Industrial needs in the area of nephrotoxicity testing have been identified, and recommendations are made at the end of this report concerning possible future initiatives.

Keywords: cell culture, in vitro, kidney, nephrotoxicity, tissue slices