Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Delivering on the potential of measuring nephron number in the clinic

Nature Reviews Nephrology volume 18, pages 271–272 (2022)Cite this article

Subjects

Decades of research have revealed that nephron number is a crucial determinant of kidney health. However, a lack of appropriate tools has limited these studies to ex vivo analyses. For the first time, techniques are emerging that might enable the use of functional nephron number as a biomarker in living humans.

In humans, nephron number is typically established at birth, but various factors can lead to nephron loss, including ageing, drug nephrotoxicity, and systemic or kidney-specific diseases1,2. Nephron number is therefore highly variable, ranging from 200,000 to >2 million when measured at autopsy1,3. Decades of autopsy studies that measured nephron number in humans, as well as recent clinical studies that estimated nephron number from biopsy samples4,5, have provided evidence that nephron number is an important biomarker and a predictor of lifetime risk of kidney disease across populations. Compensatory mechanisms in the kidney that maintain function following nephron loss can confound the early detection of kidney disease using traditional measures such as glomerular filtration rate, which often change only after substantial nephron loss. However, functional nephron number is not currently used as a clinical outcome in living individuals, primarily owing to a lack of tools to count nephrons directly in humans.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Bertram, J. F., Douglas-Denton, R. N., Diouf, B., Hughson, M. D. & Hoy, W. E. Human nephron number: implications for health and disease. Pediatr. Nephrol. 26, 1529–1533 (2011).

    Article  PubMed  Google Scholar 

  2. Luyckx, V. A. & Brenner, B. M. The clinical importance of nephron mass. J. Am. Soc. Nephrol. 21, 898–910 (2010).

    Article  PubMed  Google Scholar 

  3. Nyengaard, J. R. & Bendtsen, T. F. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat. Rec. 232, 194–201 (1992).

    CAS  Article  PubMed  Google Scholar 

  4. Denic, A. et al. Single-nephron glomerular filtration rate in healthy adults. N. Engl. J. Med. 376, 2349–2357 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sasaki, T. et al. Estimation of nephron number in living humans by combining unenhanced computed tomography with biopsy-based stereology. Sci. Rep. 9, 14400 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Morozov, D. et al. Estimating nephron number from biopsies: impact on clinical studies. J. Am. Soc. Nephrol. 33, 39–48 (2022).

    Article  PubMed  Google Scholar 

  7. Baldelomar, E. J., Charlton, J. R., Beeman, S. C. & Bennett, K. M. Measuring rat kidney glomerular number and size in vivo with MRI. Am. J. Physiol. Renal Physiol. 314, F399–F406 (2018).

    Article  PubMed  Google Scholar 

  8. Puelles, V. G., Combes, A. N. & Bertram, J. F. Clearly imaging and quantifying the kidney in 3D. Kidney Int. 100, 780–786 (2021).

    Article  PubMed  Google Scholar 

  9. Xie, L. et al. Micro-CT imaging and structural analysis of glomeruli in a model of adriamycin-induced nephropathy. Am. J. Physiol. Renal Physiol. 316, F76–F89 (2019).

    CAS  Article  PubMed  Google Scholar 

  10. Baldelomar, E. J. et al. Mapping nephron mass in vivo using positron emission tomography. Am. J. Physiol. Renal Physiol. 320, F183–F192 (2021).

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA

    Kevin M. Bennett & Edwin J. Baldelomar

  2. Division of Nephrology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA

    Jennifer R. Charlton

Authors
  1. Kevin M. Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edwin J. Baldelomar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer R. Charlton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin M. Bennett.

Ethics declarations

Competing interests

K.M.B. and J.R.C. own Sindri Technologies, LLC. K.M.B. owns Nephrodiagnostics, LLC. K.M.B. and E.J.B. own XN Biotechnologies, LLC. K.M.B. has a sponsored research agreement with Johnson & Johnson Corp. J.R.C. is a consultant for Medtronics.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bennett, K.M., Baldelomar, E.J. & Charlton, J.R. Delivering on the potential of measuring nephron number in the clinic. Nat Rev Nephrol 18, 271–272 (2022). https://doi.org/10.1038/s41581-022-00560-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41581-022-00560-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing