Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

Abstract

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.

Effect of Drugs on Renal Development

“…Similar alterations are found in the offspring of pregnant rats treated with an aminoglycoside (16). Such offspring have also been shown to have a lower nephron number and develop subsequent glomerulosclerosis with aging (17)(18)(19). In line with these findings, it has been shown that organ culture of early metanephroi in media supplemented with gentamicin also leads to impaired nephron formation (20).…”

The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis

“…However, we cannot exclude the possibility that pathological changes might occur over a longer time or if the reduction in glomerular number were more marked, as in uninephrectomy. In a rat model of oligonephronia induced in utero by gentamicin and using descriptive histological techniques only, mesangial lesions and glomerular sclerosis were more common than in control animals at 24 months [31]. A parallel may be drawn with renal transplant donors, where longitudinal studies have shown no adverse effects in the early years after nephrectomy [32] but an increased prevalence of microalbuminuria and hypertension after 12-31 years [33].…”

Study of the morphologic variants of focal segmental glomerulosclerosis: a Brazilian report

“…Given that it is well known the bigger incidence in black race and close resemblance to HIV-associated nephropathy, a search for possible viral etiology and socioeconomic influences appears justified. Merlet-Bénichou et al has found reduced numbers of glomeruli and larger glomerular volumes in newborn rats exposed to toxins in utero and in infants born with small placentas and low birth weights; these observations suggest that socioeconomic differences, such as poor nutrition or exposure to toxins during gestation, might affect the developing kidney and result in a reduced glomerular population with larger glomerular volume (6,13) .…”