GENTAMICIN ADMINISTERED DURING GESTATION ALTERS GLOMERULAR-BASEMENT-MEMBRANE DEVELOPMENT

Gentamicin during gestation alters glomerular basement membrane develo pment. A drug-induced nephrotoxicity was described for neonates after gentamicin was given intraperitoneally to pregnant Wistar rats; glomer ular alterations and changes in permselectivity were important. We inv estigated the ultrastructure of the glomerular basement membrane (GBM) , the arrangement of anionic sites, and the urinary proteins at two ag es, with 1-day- and 12-month-old control and prenatally exposed animal s. For neonates, the pattern of glomerular differentiation was similar , anionic sites were made of heparan sulfate proteoglycans, and the GB M had the same total thickness in both groups. After transplacental ge ntamicin exposure, the lamina densa was larger; the laminae rarae were thinner; the density of anionic sites was increased; the levels of hy droxyproline, sulfate, and hexuronic acid in the kidney were increased ; and the immunoelectrophoresis of urinary proteins was abnormal. For adults, prenatal exposure to gentamicin led to altered juxta-medullary glomeruli with a larger GBM and abundant anionic sites, especially in the lamina densa, and to a protein excretion different from that of c ontrols. Thus, gentamicin administered during pregnancy leads to perma nent alterations of the GBM with modifications of both the layers and the anionic sites, possibly because of a perturbed protein metabolism. These altered glomeruli are at risk during life and could be the star ting point for a kidney disease.