Skip to main content

Advertisement

SpringerLink
Log in

Safety in glomerular numbers

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

Abstract

A low nephron number is, according to Brenner’s hyperfiltration hypothesis, associated with hypertension, glomerular damage and proteinuria, and starts a vicious cycle that ends in renal failure over the long term. Nephron endowment is set during foetal life, and there is no formation of nephrons after 34–36 weeks of gestation, indicating that many factors before that time-point may have an impact on kidney development and reduce nephron numbers. Such factors include maternal malnutrition, stress, diseases, such as diabetes, uteroplacental insufficiency, maternal and neonatal drugs and premature birth. However, other congenital anomalies, such as renal hypoplasia, unilateral renal agenesis or multicystic dysplastic kidney, may also lead to a reduced nephron endowment, with an increased risk for hypertension, renal dysfunction and the need for renal replacement therapy. This review focusses on the causes and consequences of a low nephron endowment and will illustrate why there is safety in glomerular numbers.

•

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

References

  1. Brenner BM, Lawler EV, Mackenzie HS (1996) The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 49:1774–1777

    Article  PubMed  CAS  Google Scholar 

  2. Brenner, B. M. (2008) Brenner and Rector's the kidney, 8th edn. Saunders, Elsevier, Philadelphia, pp 3–24

    Google Scholar 

  3. Bertram JF, Douglas-Denton RN, Diouf B, Hughson MD, Hoy WE (2011) Human nephron number: implications for health and disease. Pediatr Nephrol 26:1529–1533

    Article  PubMed  Google Scholar 

  4. Kerecuk L, Schreuder MF, Woolf AS (2008) Renal tract malformations: perspectives for nephrologists. Nat Clin Pract Nephrol 4:312–325

    Article  PubMed  Google Scholar 

  5. Nakayama M, Nozu K, Goto Y, Kamei K, Ito S, Sato H, Emi M, Nakanishi K, Tsuchiya S, Iijima K (2010) HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 25:1073–1079

    Article  PubMed  Google Scholar 

  6. Heilmann M, Neudecker S, Wolf I, Gubhaju L, Sticht C, Schock-Kusch D, Kriz W, Bertram JF, Schad LR, Gretz N (2012) Quantification of glomerular number and size distribution in normal rat kidneys using magnetic resonance imaging. Nephrol Dial Transplant 27:100–107

    Article  PubMed  Google Scholar 

  7. Nyengaard JR, Bendtsen TF (1992) Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 232:194–201

    Article  PubMed  CAS  Google Scholar 

  8. Dotsch J, Plank C, Amann K (2012) Fetal programming of renal function. Pediatr Nephrol 27:513–520

    Article  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. Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE (2006) Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 69:671–678

    Article  PubMed  CAS  Google Scholar 

  11. Schreuder MF, Nauta J (2007) Prenatal programming of nephron number and blood pressure. Kidney Int 72:265–268

    Article  PubMed  CAS  Google Scholar 

  12. Douglas-Denton R, Moritz KM, Bertram JF, Wintour EM (2002) Compensatory renal growth after unilateral nephrectomy in the ovine fetus. J Am Soc Nephrol 13:406–410

    PubMed  Google Scholar 

  13. Westland R, Schreuder MF, Bokenkamp A, Spreeuwenberg MD, van Wijk JA (2011) Renal injury in children with a solitary functioning kidney—the KIMONO study. Nephrol Dial Transplant 26:1533–1541

    Article  PubMed  Google Scholar 

  14. Mogensen CE (1990) Prediction of clinical diabetic nephropathy in IDDM patients. Alternatives to microalbuminuria? Diabetes 39:761–767

    Article  PubMed  CAS  Google Scholar 

  15. Rossing P, De ZD (2011) Need for better diabetes treatment for improved renal outcome. Kidney Int Suppl S28–S32

  16. Sanna-Cherchi S, Ravani P, Corbani V, Parodi S, Haupt R, Piaggio G, Innocenti ML, Somenzi D, Trivelli A, Caridi G, Izzi C, Scolari F, Mattioli G, Allegri L, Ghiggeri GM (2009) Renal outcome in patients with congenital anomalies of the kidney and urinary tract. Kidney Int 76:528–533

    Article  PubMed  Google Scholar 

  17. Ibrahim HN, Foley R, Tan L, Rogers T, Bailey RF, Guo H, Gross CR, Matas AJ (2009) Long-term consequences of kidney donation. N Engl J Med 360:459–469

    Article  PubMed  CAS  Google Scholar 

  18. Larsson L, Aperia A, Wilton P (1980) Effect of normal development on compensatory renal growth. Kidney Int 18:29–35

    Article  PubMed  CAS  Google Scholar 

  19. Corbani V, Ghiggeri GM, Sanna-Cherchi S (2011) 'Congenital solitary functioning kidneys: which ones warrant follow-up into adult life?'. Nephrol Dial Transplant 26:1458–1460

    Article  PubMed  Google Scholar 

  20. Barker DJ, Osmond C (1986) Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1:1077–1081

    Article  PubMed  CAS  Google Scholar 

  21. Barker DJ (2006) Adult consequences of fetal growth restriction. Clin Obstet Gynecol 49:270–283

    Article  PubMed  Google Scholar 

  22. Hughson M, Farris AB, 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 

  23. Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ (2000) Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med 160:1472–1476

    Article  PubMed  CAS  Google Scholar 

  24. White SL, Perkovic V, Cass A, Chang CL, Poulter NR, Spector T, Haysom L, Craig JC, Salmi IA, Chadban SJ, Huxley RR (2009) Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis 54:248–261

    Article  PubMed  Google Scholar 

  25. Schreuder M, Delemarre-van de Waal H, van Wijk A (2006) Consequences of intrauterine growth restriction for the kidney. Kidney Blood Press Res 29:108–125

    Article  PubMed  CAS  Google Scholar 

  26. Ozanne SE, Hales CN (2004) Lifespan: catch-up growth and obesity in male mice. Nature 427:411–412

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. Painter RC, Roseboom TJ, van Montfrans GA, Bossuyt PM, Krediet RT, Osmond C, Barker DJ, Bleker OP (2005) Microalbuminuria in adults after prenatal exposure to the dutch famine. J Am Soc Nephrol 16:189–194

    Article  PubMed  Google Scholar 

  29. Hult M, Tornhammar P, Ueda P, Chima C, Bonamy AK, Ozumba B, Norman M (2010) Hypertension, diabetes and overweight: looming legacies of the Biafran famine. PLoS One 5:e13582

    Article  PubMed  Google Scholar 

  30. Bhat PV, Manolescu DC (2008) Role of vitamin A in determining nephron mass and possible relationship to hypertension. J Nutr 138:1407–1410

    PubMed  CAS  Google Scholar 

  31. Koleganova N, Piecha G, Ritz E, Becker LE, Muller A, Weckbach M, Nyengaard JR, Schirmacher P, Gross-Weissmann ML (2011) Both high and low maternal salt intake in pregnancy alter kidney development in the offspring. Am J Physiol Renal Physiol 301:F344–F354

    Article  PubMed  CAS  Google Scholar 

  32. Drake KA, Sauerbry MJ, Blohowiak SE, Repyak KS, Kling PJ (2009) Iron deficiency and renal development in the newborn rat. Pediatr Res 66:619–624

    Article  PubMed  CAS  Google Scholar 

  33. Tomat AL, Inserra F, Veiras L, Vallone MC, Balaszczuk AM, Costa MA, Arranz C (2008) Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney. Am J Physiol Regul Integr Comp Physiol 295:R543–R549

    Article  PubMed  CAS  Google Scholar 

  34. Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva A, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682

    Article  PubMed  Google Scholar 

  35. Tran S, Chen YW, Chenier I, Chan JS, Quaggin S, Hebert MJ, Ingelfinger JR, Zhang SL (2008) Maternal diabetes modulates renal morphogenesis in offspring. J Am Soc Nephrol 19:943–952

    Article  PubMed  CAS  Google Scholar 

  36. Chen YW, Chenier I, Tran S, Scotcher M, Chang SY, Zhang SL (2010) Maternal diabetes programs hypertension and kidney injury in offspring. Pediatr Nephrol 25:1319–1329

    Article  PubMed  Google Scholar 

  37. Davis EM, Peck JD, Thompson D, Wild RA, Langlois P (2010) Maternal diabetes and renal agenesis/dysgenesis. Birth Defects Res A Clin Mol Teratol 88:722–727

    Article  CAS  Google Scholar 

  38. Schreuder MF, Renkema KY (2011) Association between maternal diabetes and renal malformations in the offspring: more than environmental factors. Birth Defects Res A Clin Mol Teratol 91:125

    Google Scholar 

  39. Schreuder MF, Bueters RR, Huigen MC, Russel FG, Masereeuw R, van den Heuvel LP (2011) Effect of drugs on renal development. Clin J Am Soc Nephrol 6:212–217

    Article  PubMed  CAS  Google Scholar 

  40. Seckl JR (2004) Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 151 [Suppl 3]:U49–U62

    Article  PubMed  CAS  Google Scholar 

  41. Singh RR, Cullen-McEwen LA, Kett MM, Boon WM, Dowling J, Bertram JF, Moritz KM (2007) Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring. J Physiol 579:503–513

    Article  PubMed  CAS  Google Scholar 

  42. Vieau D, Sebaai N, Leonhardt M, Dutriez-Casteloot I, Molendi-Coste O, Laborie C, Breton C, Deloof S, Lesage J (2007) HPA axis programming by maternal undernutrition in the male rat offspring. Psychoneuroendocrinology 32 [Suppl 1]:S16–S20

    Article  PubMed  CAS  Google Scholar 

  43. Guron G, Friberg P (2000) An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens 18:123–137

    Article  PubMed  CAS  Google Scholar 

  44. Gubler MC, Antignac C (2010) Renin-angiotensin system in kidney development: renal tubular dysgenesis. Kidney Int 77:400–406

    Article  PubMed  CAS  Google Scholar 

  45. Woods LL, Rasch R (1998) Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats. Am J Physiol 275:R1593–R1599

    PubMed  CAS  Google Scholar 

  46. De Curtis M, Rigo J (2004) Extrauterine growth restriction in very-low-birthweight infants. Acta Paediatr 93:1563–1568

    Article  PubMed  Google Scholar 

  47. Rodriguez MM, Gomez A, Abitbol C, Chandar J, Montane B, Zilleruelo G (2005) Comparative renal histomorphometry: a case study of oligonephropathy of prematurity. Pediatr Nephrol 20:945–949

    Article  PubMed  Google Scholar 

  48. Keijzer-Veen MG, Finken MJ, Nauta J, Dekker FW, Hille ET, Frolich M, Wit JM, van der Heijden AJ (2005) Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in The Netherlands. Pediatrics 116:725–731

    Article  PubMed  Google Scholar 

  49. Alwasel SH, Ashton N (2009) Prenatal programming of renal sodium handling in the rat. Clin Sci (Lond) 117:75–84

    Article  CAS  Google Scholar 

  50. Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005) Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 20:579–584

    Article  PubMed  Google Scholar 

  51. Ashton N, Al Wasil SH, Bond H, Berry JL, Denton J, Freemont AJ (2007) The effect of a low-protein diet in pregnancy on offspring renal calcium handling. Am J Physiol Regul Integr Comp Physiol 293:R759–R765

    Article  PubMed  CAS  Google Scholar 

  52. Alwasel SH, Sahajpal V, Ashton N (2010) Renal magnesium handling is not subject to developmental programming. Kidney Blood Press Res 33:94–99

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

MFS is supported by the Dutch Kidney Foundation (KJPB.08.06).

Open Access

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, 804, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    Michiel F. Schreuder

Authors
  1. Michiel F. Schreuder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michiel F. Schreuder.

Additional information

Answers

1. b.

2. c. (Neonates born before termination of nephrogenesis, i.e. prematurely, will show postnatal formation of nephrons, even though this will be at a reduced level)

3. a.

4. e.

5. d.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schreuder, M.F. Safety in glomerular numbers. Pediatr Nephrol 27, 1881–1887 (2012). https://doi.org/10.1007/s00467-012-2169-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-012-2169-x

Keywords

Search

Navigation