Long-term effects of mild oligonephronia induced in utero by gentamicin in the rat

Pediatr Res. 1991 Nov;30(5):450-6. doi: 10.1203/00006450-199111000-00011.

Abstract

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.

MeSH terms

  • Abnormalities, Drug-Induced / pathology*
  • Abnormalities, Drug-Induced / physiopathology
  • Age Factors
  • Animals
  • Female
  • Gentamicins / toxicity*
  • Glomerular Filtration Rate
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glomerulosclerosis, Focal Segmental / physiopathology
  • Hypertrophy
  • Maternal-Fetal Exchange
  • Nephrons / abnormalities*
  • Nephrons / pathology
  • Nephrons / physiopathology
  • Pregnancy
  • Rats
  • Rats, Inbred Strains

Substances

  • Gentamicins