Long-term effects of mild oligonephronia induced in utero by gentamicin in the rat.
Renal clearance studies and morphologic observations were performed in rats aged 14, 21, and 28 d and 3, 6, 9, and 12 mo born with a 20% reduction in nephron number after administration of 75 mg/kg/d of gentamicin to their mothers during the second half of gestation. Gentamicin was still present in urine 3 mo after birth. Morphologic damage characteristic of gentamicin accumulation was observed in the kidney on d 14 and 21. Adequate compensatory adaptation to oligonephronia occurred for glomerular function within 14 d of birth, but tubular phosphate reabsorption was significantly low on d 21. On d 28, no evidence of histologic or functional damage to the kidney was observed. At 3 mo, mesangial lesions were observed in rats of the gentamicin group, whereas they were rarely present in 6-mo-old control rats. Furthermore, glomerular sclerotic lesions were already evident in about 5% of the juxtamedullary nephrons. The same percentage of injured nephrons was not observed before 12 mo in controls. Complementary morphologic data obtained in 24-mo-old rats showed that glomerulosclerosis involved 40% of the juxtamedullary nephron population at this age in animals of the gentamicin group versus 21% in controls. It is concluded that in the young rats born with oligonephronia of gentamicin-treated mothers neither the gentamicin remaining in the kidney cells nor the injuries it caused them prevented compensatory adaptation of the kidney to a reduced number of nephrons. However, although this oligonephronia was mild, it might have been sufficient to cause early development of glomerular sclerosis in the adults.
Gilbert
T
T
Unité de Recherches sur le Développement Normal et Pathologique des Fonctions Epithéliales, INSERM U 319, Université Paris 7, France.
Lelievre-Pegorier
M
M
Merlet-Benichou
C
C
D000014:Abnormalities, Drug-Induced / Q000473:pathology* / Q000503:physiopathology; D000367:Age Factors; D000818:Animals; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D008431:Maternal-Fetal Exchange; D009399:Nephrons / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins