Abstract
Intrauterine growth retardation (IUGR) was induced in Sprague-Dawley rats by partial artery ligation of one uterine horn in the mother on day 17 of gestation or by feeding the mother a 5% protein diet from day 8 of gestation. The controls were pups of the contralateral uterine horn or pups born to mothers fed a normal (22%) protein diet. The number of nephrons present at birth and the final number of nephrons in 2-week-old rats were counted throughout the entire kidney. The number of nephrons present at birth and the final number of nephrons were significantly correlated with birth weight for growth-retarded rats of both groups and their corresponding controls (P<0.02 for the poorest correlation). Clearance experiments and morphometric studies of 2-week-old rats born to mothers with uterine artery ligation indicated that, despite a large compensatory hypertrophy of the nephrons in those animals born with a nephron deficit of about 30%, the overal renal function was impaired. We conclude that IUGR is accompanied by a nephron deficit which may not be fully compensated for within the first weeks after birth.
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Royer P, Habib R, Mathieu H, Courtecuisse V (1962) L'hypoplasie rénale bilatérale congénitale avec réduction du nombre et hypertrophie des néphrons chez l'enfant. Ann Pediatr (Paris) 38: 753–766
Royer P, Habib R, Leclerc F (1967) L'hypoplasie rénale bilatérale avec oligoméganéphronie. Proceedings of the 3rd International Congress of Nephrology. Karger, Basel, pp 251–275
Van Acker KJ, Vincke H, Quatacker J, Senesael L, Van Den Brande J (1971) Congenital oligonephronic renal hypoplasia with hypertrophy of nephrons (oligonephronia). Arch Dis Child 46: 321–326
Bernstein J, Meyer R (1964) Some speculations on the nature and significance of developmentally small kidneys (renal hypoplasia). Nephron 1:137–143
Mc Graw M, Poucell S, Sweet J, Baumal R (1984) The significance of focal segmental glomerulosclerosis in oligomeganephronia. Int J Pediatr Nephrol 5:67–72
Gilbert T, Lelièvre-Pégorier M, Merlet-Bénichou C (1991) Long-term effects of mild oligonephronia induced in utero by gentamicin in the rat. Pediatr Res 30:450–456
Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1: 335–347
Gilbert T, Lelièvre-Pégorier M, Maliénou R, Meulemans A, Merlet-Bénichou C (1987) Effects of prenatal and postnatal exposure to gentamicin on renal differentiation in the rat. Toxicology 43:301–313
Gilbert T, Nabarra B, Merlet-Bénichou C (1988) Light and electron microscopic analysis of the kidney in newborn rats exposed to gentamicin in utero. Am J Pathol 130:33–43
Cavalier S, Moreau E, Gilbert T, Merlet-Bénichou C (1992) In vitro effect of gentamicin on renal differentiation in the rat. Renal Physiol Biochem 15:196
Zeman FJ (1968) Effects of maternal protein restriction on the kidney of the newborn young of rats. J Nutr 94:111–116
Sandstrom DJ, Troy JL, Brenner BM, Rennke HG (1990) Effect of maternal dietary protein content on nephron development in the rat and progressive glomerulosclerosis following nephrectomy. J Am Soc Nephrol 1:295
Larsson L, Aperia A, Wilton P (1980) Effect of normal development on compensatory renal growth. Kidney Int 18:29–35
Wigglesworth JS (1964) Experimental growth retardation in the foetal rat. J Pathol Bacterial 88:1–13
Damadian RV, Shawayri E, Bricker NS (1965) On the existence of non-urine forming nephrons in the diseased kidney of the dog. J Lab Clin Med 65:26–39
Rouffignac C de, Deiss S, Bonvalet JP (1970) Détermination du taux individuel de filtration glomérulaire des néphrons accessibles et inaccessibles à la microponction. Pflugers Arch 315:273–290
Merlet-Bénichou C, Pégorier M, Muffat-Joly M, Augeron C (1981) Functional and morphologic patterns of renal maturation in the developing guinea-pig. Am J Physiol 241:F618-F624
Zeman FJ, Stanbrough EC (1969) Effect of maternal protein deficiency on cellular development in the fetal rat. J Nutr 99: 274–282
Rosso P (1977) Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of alpha-amino isobutyric acid. J Nutr 107:2002–2005
Venkatachalam PS, Ramanathan KS (1964) Effect of protein deficiency during gestation and lactation on body weight and composition of offspring. J Nutr 84:38–42
Goldstein RS, Hook JB, Bond JT (1979) The effects of maternal protein deprivation on renal development and function in neonatal rats. J Nutr 109:949–957
Rosso P, Streeter MR (1979) Effects of food or protein restriction on plasma volume expansion in pregnant rats. J Nutr 109: 1887–1892
Grosvenor MB, Zeman FJ (1983) In vitro amino acid transport by renal tubules of prenatally protein-deprived fetal rats. J Nutr 113: 1513–1520
Minkowski A, Chanez C (1983) Some pathophysiologic changes in experimental intrauterine malnutrition. In: Kretchmer N, Minkowski A (eds) Nutritional adaptation of the gastrointestinal tract of the newborn. Raven, New York, pp 131–149
Dawes GS (1968) The fetal circulation. In: Dawes GS (ed) Foetal and neonatal physiology. Year Book Medical, Chicago, pp 91–105
Gilbert T, Lelièvre-Pégorier M, Merlet-Bénichou C (1990) Immediate and long-term renal effects of fetal exposure to gentamicin. Pediatr Nephrol 4:445–450
Brenner BM (1985) Nephron adaptation to renal injury or ablation. Am J Physiol 249:F324-F337
Leroy B, Josset P, Morgan G, Costil J, Merlet-Bénichou C (1992) Intrauterine growth retardation (IUGR) and nephron deficit: preliminary study in man. Pediatr Nephrol 6:21C
Scheinman JI, Abelson HT (1970) Bilateral renal hypoplasia with oligonephronia. J Pediatr 76:369–376
Whincup PH, Cook DG, Shaper AG (1989) Early influences on blood pressure: a study of children aged 5–7 years. BMJ 299: 587–591
Law CM, Barker DJP, Bull AR, Osmond C (1991) Maternal and fetal influences on blood pressure. Arch Dis Child 66:1291–1295
Barker DJP, Osmond C, Winter PD, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet ii:577–580
Murdaugh HV, Fetterman GH (1971) Smal kidneys, polyuria, growth retardation, and renal failure. J Pediatr 79:858–867
Kiprov DD, Colvin RB, Mc Cluskey RT (1982) Focal and segmental glomerulosclerosis and proteinuria associated with unilateral renal agenesis. Lab Invest 46:275–281
Hakim RM, Goldszer RC, Brenner BM (1984) Hypertension and proteinuria: long term sequelae of uninephrectomy in humans. Kidney Int 25:930–936
Talseth T, Fauchald P, Skrede S, Djoseland O, Berg KJ, Stenstrom J, Heilo A, Brodwall EK, Flatmark A (1986) Long-term blood pressure and renal function in kidney donors. Kidney Int 29:1072–1076
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Merlet-Bénichou, C., Gilbert, T., Muffat-Joly, M. et al. Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol 8, 175–180 (1994). https://doi.org/10.1007/BF00865473
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DOI: https://doi.org/10.1007/BF00865473