Skip to main content

Advertisement

SpringerLink
Log in

Low nephron number—a new cardiovascular risk factor in children?

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

There is increasing evidence that primary hypertension, coronary heart disease, and other aspects of the so-called metabolic syndrome that develop in adulthood are primed in fetal life or early postnatally. The identification of this phenomenon, also known as prenatal or fetal programming, and the detailed characterization of the underlying pathomechanisms will greatly influence the understanding of these diseases. The present paper reviews recent experimental and clinical evidence that low nephron number, found in patients with renal dysplasia and low birth weight, is a risk factor for cardiovascular disease in later life. Therefore, it is important to identify children at risk as early as possible in order to treat them early and to prevent the development of end-organ damage. This could be an important goal for pediatrics in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Luft FC (2004) Present status of genetic mechanisms in hypertension. Med Clin North Am 88:1–18

    CAS  PubMed  Google Scholar 

  2. Rettig R, Folberth C, Stauss H, Kopf D, Waldherr R, Unger T (1990) Role of the kidney in primary hypertension: a renal transplantation study in rats. Am J Physiol 258:F606–F611

    CAS  PubMed  Google Scholar 

  3. Strandgaard S, Hansen U (1986) Hypertension in renal allograft recipients may be conveyed by cadaveric kidneys from donors with subarachnoidal haemorrhage. BMJ 292:1041–1044

    CAS  PubMed  Google Scholar 

  4. Curtis JJ, Luke RG, Dustan HP, Kashgarian M, Whelchel JD, Jones P, Diethelm AG (1983) Remission of essential hypertension after renal transplantation. N Engl J Med 309:1009–1015

    CAS  PubMed  Google Scholar 

  5. Mei-Zahav M, Korzets Z, Cohen I, Kessler O, Rathaus V, Wolach B, Pomeranz A (2001) Ambulatory blood pressure monitoring in children with a solitary kidney—a comparison between unilateral renal agenesis and uninephrectomy. Blood Press Monit 6:263

    Article  CAS  PubMed  Google Scholar 

  6. Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure: less of one, more of the other? Am J Hypertens 1:335–347

    CAS  PubMed  Google Scholar 

  7. Woods LL (1999) Neonatal uninephrectomy causes hypertension in adult rats. Am J Physiol 276:R974–R978

    CAS  PubMed  Google Scholar 

  8. Moritz KM, Wintour EM, Dodic M (2002) Fetal uninephrectomy leads to postnatal hypertension and compromised renal function. Hypertension 39:1071–1076

    Article  CAS  PubMed  Google Scholar 

  9. Keller G, Zimmer G, Mall G, Ritz E, Amann K (2003) Nephron number in patients with primary hypertension. N Engl J Med 348:101–108

    Article  PubMed  Google Scholar 

  10. Ingelfinger JR (2003) Is microanatomy destiny? N Engl J Med 348:99–100

    Article  PubMed  Google Scholar 

  11. Cullen-McEwen LA, Kett MM, Dowling J, Anderson WP, Bertram JF (2003) Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice. Hypertension 41:335–340

    Article  CAS  PubMed  Google Scholar 

  12. Merlet-Benichou C (1999) Influence of fetal environment on kidney development. Int J Dev Biol 43:453–456

    CAS  PubMed  Google Scholar 

  13. Wintour EM, Moritz KM, Johnson K, Ricardo S, Samuel CS, Dodic M (2003) Reduced nephron number in adult sheep, hypertensive as a result of prenatal glucocorticoid treatment. J Physiol 549:929–935

    Google Scholar 

  14. Amri K, Freund N, Van Huyen JP, Merlet-Benichou C, Lelievre-Pegorier M (2001) Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney. Diabetes 50:1069–1075

    CAS  PubMed  Google Scholar 

  15. Regina S, Lucas R, Miraglia SM, Zaladek Gil F, Machado Coimbra T (2001) Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis 37:467–476

    CAS  PubMed  Google Scholar 

  16. Mitchell EK, Louey S, Cock ML, Harding R, Black MJ (2004) Nephron endowment and filtration surface area in the kidney after growth restriction of fetal sheep. Pediatr Res 55:769–773

    Article  PubMed  Google Scholar 

  17. Vehaskari MV, Aviles DH, Manning J (2001) Prenatal programming of adult hypertension in the rat. Kidney Int 59:238–245

    Article  CAS  PubMed  Google Scholar 

  18. Wintour EM, Johnson K, Koukoulas I, Moritz K, Tersteeg M, Dodic M (2003) Programming the cardiovascular system, kidney and the brain—a review. Placenta 24 [Suppl A]:S65–S71

  19. Manalich R, Reyes L, Herrera M, Melendi C, Fundora I (2000) Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58:770–773

    Article  PubMed  Google Scholar 

  20. Hughson M, Farris AB 3rd, Douglas-Denton R, Hoy WE, Bertram JF (2003) Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 63:2113–2122

    Article  PubMed  Google Scholar 

  21. Battista MC, Oligny LL, St-Louis J, Brochu M (2002) Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood. Am J Physiol Endocrinol Metab 283:E124–E131

    CAS  PubMed  Google Scholar 

  22. Manning J, Vehaskari VM (2001) Low birth weight-associated adult hypertension in the rat. Pediatr Nephrol 16:417–422

    Article  CAS  PubMed  Google Scholar 

  23. Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142:2841–2853

    Article  CAS  PubMed  Google Scholar 

  24. Bassan H, Trejo LL, Kariv N, Bassan M, Berger E, Fattal A, Gozes I, Harel S (2000) Experimental intrauterine growth retardation alters renal development. Pediatr Nephrol 5:192–195

    Article  Google Scholar 

  25. Woods LL, Weeks DA, Rasch R (2004) Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int 65:1339–1348

    Article  PubMed  Google Scholar 

  26. Manning J, Beutler K, Knepper MA, Vehaskari VM (2002) Upregulation of renal BSC1 and TSC in prenatally programmed hypertension. Am J Physiol Renal Physiol 283:F202–F206

    CAS  PubMed  Google Scholar 

  27. Bauer R, Walter B, Ihring W, Kluge H, Lampe V, Zwiener U (2000) Altered renal function in growth-restricted newborn piglets. Pediatr Nephrol 14:735–739

    Google Scholar 

  28. Bauer R, Walter B, Bauer K, Klupsch R, Patt S, Zwiener U (2002) Intrauterine growth restriction reduces nephron number and renal excretory function in newborn piglets. Acta Physiol Scand 176:83–90

    Article  CAS  PubMed  Google Scholar 

  29. Langley-Evans SC, Sherman RC, Welham SJ, Nwagwu MO, Gardner DS, Jackson AA (1999) Intrauterine programming of hypertension: the role of the renin-angiotensin system. Biochem Soc Trans 27:88–93

    Google Scholar 

  30. Kingdom JC, Hayes M, McQueen J, Howatson AG, Lindop GB (1999) Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney. Kidney Int 55:424–429

    Article  CAS  PubMed  Google Scholar 

  31. Houang M, Morineau G, Bouc Y le, Fiet J, Gourmelen M (1999) The cortisol-cortisone shuttle in children born with intrauterine growth retardation. Pediatr Res 46:189–193

    CAS  PubMed  Google Scholar 

  32. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170

    Article  CAS  PubMed  Google Scholar 

  33. Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL (1997) Sympathetic and cardiorenal actions of leptin. Hypertension 30 [Suppl]:619–623

  34. Barker DJ, Osmond C, Law CM (1989) The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. J Epidemiol Community Health 43:237–240

    CAS  PubMed  Google Scholar 

  35. Law CM, Shiell AW, Newsome CA, Syddall HE, Shinebourne EA, Fayers PM, Martyn CN, Swiet M de (2002) Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation 105:1088–1092

    Article  CAS  PubMed  Google Scholar 

  36. Zhang J, Brenner RA, Klebanoff MA (2001) Differences in birth weight and blood pressure at age 7 years among twins. Am J Epidemiol 153:779–782

    Article  CAS  PubMed  Google Scholar 

  37. Williams S, Poulton R (2002) Birth size, growth, and blood pressure between the ages of 7 and 26 years: failure to support the fetal origins hypothesis. Am J Epidemiol 155:849–852

    Article  PubMed  Google Scholar 

  38. Fattal-Valevski A, Bernheim J, Leitner Y, Redianu B, Bassan H, Harel S (2001) Blood pressure values in children with intrauterine growth retardation. Isr Med Assoc J 3:805–808

    CAS  PubMed  Google Scholar 

  39. Whincup PH, Bredow M, Payne F, Sadler S, Golding J (1999) Size at birth and blood pressure at 3 years of age. The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). Am J Epidemiol 149:730–739

    CAS  PubMed  Google Scholar 

  40. Uiterwaal CS, Anthony S, Launer LJ, Witteman JC, Trouwborst AM, Hofman A, Grobbee DE (1997) Birth weight, growth, and blood pressure: an annual follow-up study of children aged 5 through 21 years. Hypertension 30:267–271

    CAS  PubMed  Google Scholar 

  41. Law CM, Shiell AW, Newsome CA, Syddall HE, Shinebourne EA, Fayers PM, Martyn CN, Swiet M de (2002) Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation 105:1088–1092

    Article  CAS  PubMed  Google Scholar 

  42. Horta BL, Barros FC, Victora CG, Cole TJ (2003) Early and late growth and blood pressure in adolescence. J Epidemiol Community Health 57:226–230

    Article  CAS  PubMed  Google Scholar 

  43. Huxley RR, Shiell AW, Law CM (2000) The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18:815–831

    Article  CAS  PubMed  Google Scholar 

  44. Plagemann A (2003) Fetale Programmierung und Funktionelle Teratologie: Zur perinatalen Prägung dauerhaft erhöhter Disposition für das Metabolische Syndrom X. In: Zabransky S (ed) SGA-Syndrom Small for gestational Age. Jonag Verlag, Marburg, pp 49–59

  45. Rostand SG (2003) Oligonephronia, primary hypertension and renal disease: ‘is the child father to the man?’. Nephrol Dial Transplant 18:1434–1438

    Article  PubMed  Google Scholar 

  46. Tulassay T, Vasarhelyi B (2002) Birth weight and renal function. Curr Opin Nephrol Hypertens 11:347–352

    Article  PubMed  Google Scholar 

  47. Ingelfinger JR (2004) Pathogenesis of perinatal programming. Curr Opin Nephrol Hypertens 13:459–464

    CAS  PubMed  Google Scholar 

  48. Roseboom TJ, Meulen JHP van der, Ravelli ACJ, Osmond C, Barker DJP, Bleker OP (2001): Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. J Mol Cell Endocrinol 185:93–98

    Article  CAS  Google Scholar 

  49. Bouret SG, Draper SJ, Simerly RB (2004) Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304:108–115

    Article  CAS  PubMed  Google Scholar 

  50. Dötsch J, Rascher W, Meissner U (2004) Perinatal programming of appetite control by leptin? Eur J Endocrinol 151:1–3

    PubMed  Google Scholar 

Download references

Acknowledgement

This study was supported by the Deutsche Forschungsgemeinschaft (SFB 423, projects B8 and B9).

Author information

Authors and Affiliations

  1. Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstrasse 8–10, 91054 Erlangen, Germany

    Kerstin Amann

  2. Klinik für Kinder und Jugendliche, University of Erlangen-Nürnberg, Erlangen, Germany

    Christian Plank & Jörg Dötsch

Authors
  1. Kerstin Amann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Plank
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jörg Dötsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kerstin Amann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amann, K., Plank, C. & Dötsch, J. Low nephron number—a new cardiovascular risk factor in children?. Pediatr Nephrol 19, 1319–1323 (2004). https://doi.org/10.1007/s00467-004-1643-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-004-1643-5

Keywords

Search

Navigation