[Detection of drug-induced nephrotoxicity]

This is a report of a round table organized during the second meeting of Clinical Pharmacology held in Giens (France) in September 1985. At the beginning of the meeting, the clinical aspects of drug-induced nephrotoxicity were reviewed. Thus we tried to precise the real interest of the studies of proteinuria, urinary cytology, enzymuria and fractional clearances of lithium or magnesium. The most interesting part of our discussions was to know the point of view of men working in drugs companies when a renal abnormality is found during a clinical trial of a drug and when previous experimental studies did not find any renal adverse effects of the drug. It was suggested in a such situation to do particular studies. Methods generally used to study renal physiology as autoradiography micropuncture, microinjection had to be performed to localize the action of the drug along the nephron. It was also discussed of the use of isolated perfused kidney as a tool in drug disposition and the use of renal cells culture. A better understanding of the mechanisms of direct renal toxicity of drugs was obtained from the results of experimental models. It is not so easy, at the present time, to know the mechanisms of immunological drug-induced nephrotoxicity. It seems necessary to develop new experimental models. The results obtained in animals with Cl2Hg or D. Penicillamine or gold salts afford to suspect some mechanisms for these types of nephropathies. This aspect of drug induced nephropathy is more complex because there is a large interindividual variation in susceptibility to these drugs.