Skip to main content
SpringerLink
Log in

Human nephron number: implications for health and disease

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

Abstract

Several studies have shown that total nephron (glomerular) number varies widely in normal human kidneys. Whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney, numbers for individual kidneys range from approximately 200,000 to >2.5 million. Several studies have shown loss of glomeruli due to age-related glomerulosclerosis. The rates of loss vary among individuals depending upon blood pressure, diseases affecting the kidney, and other attributes of health, but most of the variation in nephron number is present at birth and is therefore developmentally determined. For example, in a relatively small study of nephron number in 15 children <3 months of age, we found that nephron number ranged from approximately 250,000 to 1.1 million. Given that no new nephrons are formed in human kidneys after approximately 36 weeks’ gestation, much interest has focused on renal function and health in individuals born with relatively low nephron endowment. Several studies have reported a direct correlation between birth weight and nephron number and an indirect association between nephron number and blood pressure. Associations between low birth weight and cardiovascular disease, including hypertension, have also been widely reported. This report provides an update on our current knowledge of human nephron number and the associations with adult health and disease.

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

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Moritz KM, Wintour EM, Black MJ, Bertram JF, Caruana G (2008) Factors influencing mammalian kidney development: implications for health in adult life. Adv Anat Embryol Cell Biol 196:1–78

    CAS  PubMed  Google Scholar 

  3. Puelles VG, Hoy WE, Hughson MD, Diouf B, Douglas-Denton RN, Bertram JF (2011) Glomerular number and size variability and risk for kidney disease. Curr Opin Nephrol Hypertens 20:7–15

    Article  Google Scholar 

  4. Bertram JF, Soosaipillai MC, Ricardo SD, Ryan GB (1992) Total numbers of glomeruli and individual glomerular cell types in the normal rat kidney. Cell Tissue Res 270(1):37–45

    Article  CAS  Google Scholar 

  5. Bertram JF (1995) Analyzing renal glomeruli with the new stereology. Int Rev Cytol 161:111–172

    Article  CAS  Google Scholar 

  6. Nyengaard JR (1999) Stereologic methods and their application in kidney research. J Am Soc Nephrol 10(5):1100–1123

    CAS  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  CAS  Google Scholar 

  8. 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  Google Scholar 

  9. Douglas-Denton RN, McNamara BJ, Hoy WE, Hughson MD, Bertram JF (2006) Does nephron number matter in the development of kidney disease? Ethn Dis 16(S2):40–45

    Google Scholar 

  10. Hoy WE, Douglas-Denton RN, Hughson MD, Cass A, Johnson K, Bertram JF (2003) A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl 83:S31–S37

    Article  Google Scholar 

  11. Hoy WE, Hughson MD, Bertram JF, Douglas-Denton R, Amann K (2005) Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol 16(9):2557–2564

    Article  Google Scholar 

  12. Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF (2006) Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int 70:104–110

    Article  CAS  Google Scholar 

  13. Hoy WE, Bertram JF, Douglas-Denton R, Zimanyi M, Samuel T, Hughson MD (2008) Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens 17:258–265

    Article  Google Scholar 

  14. Hoy WE, Ingelfinger JR, Hallan S, Hughson MD, Mott SA, Bertram JF (2010) The early development of the kidney and the implications for future health. J Dev Orig Health Dis 1:216–233

    Article  CAS  Google Scholar 

  15. Hoy WE, Hughson MD, Zimanyi M, Samuel T, Douglas-Denton R, Holden L, Mott S, Bertram JF (2010) Distribution of volumes of individual glomeruli in kidneys at autopsy: Association with age, nephron number, birth weight and body mass index. Clin Nephrol 74:S105–S112

    PubMed  Google Scholar 

  16. 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  Google Scholar 

  17. 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  CAS  Google Scholar 

  18. Hughson MD, Gobe GC, Hoy WE, Manning RD Jr, Douglas-Denton R, Bertram JF (2008) Associations of glomerular number and birth weight with clinicopathological features of African Americans and whites. Am J Kidney Dis 52(1):18–28

    Article  Google Scholar 

  19. Hughson MD, Hoy WE, Douglas-Denton RN, Zimanyi MA, Bertram JF (2010) Towards a definition of glomerulomegaly: clinical-pathological and methodological considerations. Nephrol Dial Transplant. doi:https://doi.org/10.1093/ndt/gfq688

  20. McNamara BJ, Diouf B, Hughson MD, Douglas-Denton RN, Hoy WE, Bertram JF (2008) Renal pathology, glomerular number and volume in a West African urban community. Nephrol Dial Transplant 23:2576–2585

    Article  Google Scholar 

  21. McNamara BJ, Diouf B, Hughson MD, Hoy WE, Bertram JF (2009) Associations between age, body size and nephron number with individual glomerular volumes in urban West African males. Nephrol Dial Transplant 24:1500–1506

    Article  Google Scholar 

  22. McNamara BJ, Diouf B, Douglas-Denton RN, Hughson MD, Hoy WE, Bertram JF (2010) A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans. Nephrol Dial Transplant 25:1514–1520

    Article  Google Scholar 

  23. Merlet-Bénichou C, Gilbert T, Vilar J, Moreau E, Freund N, Lelièvre-Pégorier M (1999) Nephron number: variability is the rule. Causes and consequences. Lab Invest 79:515–527

    PubMed  Google Scholar 

  24. Zhang Z, Quinlan J, Hoy W, Hughson MD, Lemire M, Hudson T, Hueber PA, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Houghton F, Bertram J, Goodyer P (2008) A common RET variant is associated with reduced newborn kidney size and function. J Am Soc Nephrol 19:2027–2034

    Article  CAS  Google Scholar 

  25. Beeman SC, Zhang M, Gubhaju L, Frakes D, Bertram JF, Wu T, Bennett K (2011) Measuring whole kidney nephron endowment using MRI. Proc 19th Ann Mtg Int Soc Mag Reson Med, Montreal

  26. Zimanyi MA, Hoy WE, Douglas-Denton RN, Hughson MD, Holden LM, Bertram JF (2009) Nephron number and individual glomerular volumes in male Caucasian and African American subjects. Nephrol Dial Transplant 24:2428–2433

    Article  Google Scholar 

  27. 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  Google Scholar 

  28. Hoy WE, Rees M, Kile E, Mathews JD, Wang Z (1999) A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int 56:1072–1077

    Article  CAS  Google Scholar 

  29. Hallan S, Euser AM, Irgens LM, Finken MJ, Holmen J, Dekker FW (2008) Effect of intrauterine growth restriction on kidney function at young adult age: the Nord Trondelag Health (HUNT 2) Study. Am J Kidney Dis 51:10–20

    Article  Google Scholar 

  30. Keijzer-Veen MG, Schrevel M, Finken MJ, Dekker FW, Nauta J, Hille ET, Frölich M, van der Heijden BJ, Dutch POPS-19 Collaborative Study Group (2005) Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol 16:2762–2768

    Article  CAS  Google Scholar 

  31. 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  CAS  Google Scholar 

  32. Vikse BE, Irgens LM, Leivestad T, Hallan S, Iversen BM (2008) Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol 19:151–157

    Article  Google Scholar 

  33. 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  Google Scholar 

  34. Hodgin JB, Rasoulpour M, Markowitz GS, D'Agati VD (2009) Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 4:71–76

    Article  Google Scholar 

Download references

Acknowledgments

Our research program was supported by funds from the National Health and Medical Research Council of Australia, Kidney Health Australia, Janssen-Cilag, the National Institutes of Health NIH 1 R01 DK065970-01, NIH Center of Excellence in Minority Health 5P20M000534-02, and the Colonial Foundation of Australia.

Author information

Authors and Affiliations

  1. Department of Anatomy and Developmental Biology, Monash University Clayton, Melbourne, Victoria, 3800, Australia

    John F. Bertram & Rebecca N. Douglas-Denton

  2. Hôpital Aristide Le Dantec, Dakar, Senegal

    Boucar Diouf

  3. Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA

    Michael D. Hughson

  4. Centre for Chronic Diseases, University of Queensland, Brisbane, Australia

    Wendy E. Hoy

Authors
  1. John F. Bertram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca N. Douglas-Denton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Boucar Diouf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael D. Hughson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wendy E. Hoy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John F. Bertram.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bertram, J.F., Douglas-Denton, R.N., Diouf, B. et al. Human nephron number: implications for health and disease. Pediatr Nephrol 26, 1529–1533 (2011). https://doi.org/10.1007/s00467-011-1843-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-011-1843-8

Keywords

Search

Navigation