ADVANTAGES AND LIMITATIONS OF THE USE OF ISOLATED KIDNEY-TUBULES IN PHARMACOTOXICOLOGY

Among the cellular models used in in vitro renal pharmacotoxicology, i solated kidney tubules, used as suspensions mainly of proximal tubules , offer important advantages. They can be prepared in large amounts un der nonsterile conditions within 1-2 h; thus, it is possible to employ a great number of experimental conditions simultaneously and to obtai n rapidly many experimental results. Kidney tubules can be prepared fr om the kidney of many animal species and also from the human kidney; g iven the very limited availability of healthy human renal tissue, it i s therefore possible to choose the most appropriate species for the st udy of a particular problem encountered in man. Kidney tubules can be used for screening and prevention of nephrotoxic effects and to identi fy their mechanisms as well as to study the renal metabolism of xenobi otics. When compared with cultured renal cell, a major advantage of ki dney tubules is that they remain differentiated. The main limitations of the use of kidney tubules in pharmacotoxicology are (1) the necessi ty to prepare them as soon as the renal tissue sample is obtained; (2) their limited viability, which is restricted to 2-3 h; (3) the inabil ity to expose them chronically to a potential nephrotoxic drug; (4) th e inability to study transepithelial transport; and (5) the uncertaint y in the extrapolation to man of the results obtained using animal kid ney tubules. These advantages and limitations of the use of human and animal kidney tubules in pharmacotoxicology are illustrated mainly by the results of experiments performed with valproate, an antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules, unl ike cultured renal cells, retain key metabolic properties is also show n to be of the utmost importance in detecting certain nephrotoxic effe cts.