Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-27T07:25:36.008Z Has data issue: false hasContentIssue false
  • English
  • Français

Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero

Published online by Cambridge University Press:  09 March 2007

Margaret O. Nwagwu ,
Anna Cook  and
Simon C. Langley-Evans
Margaret O. Nwagwu
Affiliation:
Department of University Medicine, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Anna Cook
Affiliation:
Department of University Medicine, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Simon C. Langley-Evans*
Affiliation:
University College Northampton, Boughton Green Road, Northampton NN2 7AL, UK
*
*Corresponding author: Dr Simon Langley-Evans, fax +44 (0)1604 716165, email simon.langley-evans@northampton.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CHD. Animal experiments suggest that the kidney, which is extremely vulnerable to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal haemodynamic functions following structural impairment in fetal life is proposed to require adaptations which raise systemic blood pressure and promote a more rapid progression to renal failure. Rats were fed on diets containing 180 g casein/kg (control) or 90 g casein/kg (low protein) during pregnancy. The offspring were studied in terms of blood pressure, creatinine clearance, blood urea N, plasma and urinary albumin, renal morphometry and metabolic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at all ages in the low-protein-exposed offspring, relative to control rats. Rats (4 weeks old) exposed to the low-protein diet had smaller kidneys which were shorter and wider than those of control animals. Creatinine clearance was significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenced by prenatal diet. Blood urea N, urinary output and urinary albumin excretion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a progressive deterioration of renal function in hypertensive rats exposed to mild maternal protein restriction during fetal life. This is consistent with the hypothesis that adaptations to maintain renal haemodynamic functions following impairment of fetal nephrogenesis result in an accelerated progression towards glomerulosclerosis and increased intrarenal pressures mediated by rising vascular resistance.

Keywords

KidneyHypertensionLow-protein dietsMaternal nutrition
Type
Research Article
Information
British Journal of Nutrition , Volume 83 , Issue 1 , January 2000 , pp. 79 - 85
Copyright
Copyright © The Nutrition Society 2000

References

Barker, DJP (1994) Mothers, Babies and Disease in Later Life. London: BMJ Publishing Group.Google Scholar
Bowers, CD & Wong, ET (1980) Kinetic serum creatinine assays: a critical evaluation. Clinical Chemistry 26, 555–561.CrossRefGoogle ScholarPubMed
Celsi, G, Kistner, A, Eklof, A-C, Ceccatelli, S, Aizman, R & Jacobson, S (1997) Inhibition of renal growth by prenatal dexamethasone and the programming of blood pressure in the offspring. Journal of the American Society of Nephrology 8, A1360.Google Scholar
Dahri, S, Snoeck, A, Reusens-Billen, B, Remacle, C & Hoet, JJ (1991) Islet function in offspring of mothers on low-protein diet during gestation. Diabetes 40, Suppl. 2115–120.CrossRefGoogle ScholarPubMed
Duarte, CG & Preuss, HG (1993) Assessment of renal function: glomerular and tubular. Clinics in Laboratory Medicine 13, 33–52.CrossRefGoogle ScholarPubMed
Gilbert, T, Lelievre-Pegorier, M & Merlet-Benichou, C (1991) Long term effects of mild oligonephronia induced in utero by gentamycin in the rat. Pediatric Research 30, 450–456.CrossRefGoogle ScholarPubMed
Hall, SM & Zeman, FJ (1968) Kidney function of the progeny of rats fed a low protein diet. Journal of Nutrition 95, 49–56.CrossRefGoogle ScholarPubMed
Hinchcliffe, SA, Lynch, MRJ, Sargent, PH, Howard, CV & van Zelzen, D (1992) The effect of intrauterine growth retardation on the development of renal nephrons. British Journal of Obstetrics and Gynaecology 99, 296–301.CrossRefGoogle Scholar
Konje, JC, Bell, SC, Morton, JJ, De Chazal, R & Taylor, DJ (1996) Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth. Clinical Science 91, 169–175.CrossRefGoogle ScholarPubMed
Langley, SC, Browne, RF & Jackson, AA (1994 a) Altered glucose tolerance in rats exposed to maternal low protein diets in utero. Comparative Biochemistry and Physiology 109A, 223–229.CrossRefGoogle ScholarPubMed
Langley, SC & Jackson, AA (1994) Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diet. Clinical Science 86, 217–222.CrossRefGoogle Scholar
Langley, SC, Seakins, M, Grimble, RF & Jackson, AA (1994 b) The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets. Journal of Nutrition 124, 1588–1596.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1998) Nutritional programming and the development of hypertension. In Development of the Hypertensive Phenotype: Basic and Clinical Studies. Handbook of Hypertension, vol. 19, pp. 539–574 [McCarty, R, Blizzard, DA and Chevalier, RL, editors]. Amsterdam: Elsevier.Google Scholar
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 a) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. Journal of Reproduction and Fertility 106, 307–312.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 b) Maternal protein restriction influences the programming of the rat hypothalamic–pituitary–adrenal axis. Journal of Nutrition 126, 1578–1585.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1994) In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clinical Nutrition 13, 319–324.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Sherman, RC, Welham, SJM, Nwagwu, MO, Gardner, DS & Jackson, AA (1999 a) Intrauterine programming of hypertension: the role of the renin–angiotensin system. Biochemical Society Transactions 27, 88–93.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM & Jackson, AA (1999 b) Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sciences 64, 965–974.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM, Sherman, RC & Jackson, AA (1996 c) Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clinical Science 91, 607–615.CrossRefGoogle ScholarPubMed
Luke, RG (1981) Uremia and the BUN. New England Journal of Medicine 305, 1213–1215.CrossRefGoogle ScholarPubMed
Mackenzie, HS & Brenner, BM (1995) Fewer nephrons at birth: a missing link in the etiology of essential hypertension?. American Journal of Kidney Disease 26, 91–98.CrossRefGoogle ScholarPubMed
Merlet-Benichou, C, Gilbert, T, Muffat-Joly, M, Lelievre-Pegorier, M & Leroy, B (1994) Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatric Nephrology 8, 175–180.CrossRefGoogle ScholarPubMed
Owen, WF, Lew, NL & Liu, Y (1993) The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing haemodialysis. New England Journal of Medicine 329, 1001–1006.CrossRefGoogle Scholar
Ozanne, SE, Smith, GD, Tikerpae, J & Hales, CN (1996) Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. American Journal of Physiology 270, E559–E564.Google ScholarPubMed
Pickard, CL, McCarthy, HD, Browne, RF & Jackson, AA (1996) Altered insulin response to a glucose load in rats following exposure to a low protein diet in utero. Proceedings of the Nutrition Society 55, 44A.Google Scholar
Sherman, RC & Langley-Evans, SC (1998) Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low protein diet. Clinical Science 94, 373–381.CrossRefGoogle ScholarPubMed
Smith, PK, Krohn, RI, Hermanson, GT, Mallia, AK, Gartner, FH, Provenzano, MD, Fujimoto, EK, Goelke, NM, Olson, BJ & Klenk, DC (1985) Measurement of protein using bicinchonic acid. Analytical Biochemistry 150, 76–85.CrossRefGoogle Scholar
Snoeck, A, Remacle, C, Reusens, B & Hoet, JJ (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biology of the Neonate 57, 107–118.CrossRefGoogle ScholarPubMed
Zeman, FJ (1968) Effects of maternal protein restriction on the kidney of the newborn young of rats. Journal of Nutrition 94, 111–117.CrossRefGoogle ScholarPubMed