NEPHROTOXICITY TESTING IN-VITRO - THE CURRENT SITUATION

An ECVAM task force on nephrotoxicity has been established to advise, in particular, on the follow-up to recommendations made in the ECVAM w orkshop report on nephrotoxicity testing in vitro. Since this workshop was held, in 1994, there have been several improvements in the techni ques 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 culture s 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 transepi thelial transport capacities to proximal tubules in vivo have been obt ained with primary cultures of rabbit proximal tubule cells which are grown on bicompartmental supports; in this system, transepithelial sub strate gradients are generated and the transepithelial transport of bo th organic anions and cations is highly active. This in vitro system h as been selected by ECVAM for further evaluation and prevalidation. In dustrial needs in the area of nephrotoxicity testing have been identif ied, and recommendations are made at the end of this report concerning possible future initiatives.