Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
    • Editorial Fellowship Application Process
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
    • Editorial Fellowship Application Process
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Letters to the Editor
You have accessRestricted Access

Authors’ Reply

Aleksandar Denic and Andrew D. Rule
JASN February 2021, 32 (2) 517-518; DOI: https://doi.org/10.1681/ASN.2020111615
Aleksandar Denic
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew D. Rule
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew D. Rule
  • Article
  • Info & Metrics
  • View PDF
Loading
  • nephron
  • renal morphology
  • glomerulus

We thank Seibel and colleagues1 for their thoughtful letter on the importance of nephron number. We agree that nephron number warrants investigation as a prognostic marker in the kidney cancer population.

However, we would also argue that glomerular density should not be simply viewed as a surrogate for nephron number. Certainly, this is true to some extent, as nephron number is estimated from glomerular density (calculated with stereology applied to kidney biopsy section) multiplied by cortical volume. However, we would restate this relationship in a different manner. Cortical volume can be estimated from average nephron size in the cortex (cortex per glomerulus or the reciprocal of glomerular density) multiplied by nephron number.2 The interpretation of cortex per glomerulus as a measure of average nephron size is supported by its correlation with glomerular volume (rs=0.83, P<0.001) and with mean cross-sectional tubular area (rs=0.66, P<0.001) in our study.3 A concern with interpreting cortex per glomerulus as nephron size may be that some of the volume occupied by the cortex is not functioning nephrons but rather, interstitial fibrosis/tubular atrophy (IF/TA). However, even after excluding regions of IF/TA, the correlation of nonfibrotic cortex per glomerulus with glomerular volume (rs=0.84, P<0.001) and cross-sectional tubular area (rs=0.66, P<0.001) were not meaningfully different nor was the prediction of CKD progression.3

We argue that cortex per glomerulus, glomerular volume, and tubular cross-sectional area are all measures of nephron size, but there are also important differences and limitations with each. Glomerular volume does not capture the volume occupied by tubules, and only about 4% of the cortical volume is due to volume from glomeruli.2 Some clinical factors, such as aging, appear to be associated with an increase in the size of tubules but not the size of glomeruli.4 The cross-sectional tubular area does not account for the different orientations, differing segments, and/or differing lengths of the tubules. Cortex per glomerulus may better account for the three-dimensional volume occupied by tubules in the cortex, but it does not exclude the volume occupied by vessels and IF/TA. None of these measures account for the volume occupied by nephron in the medulla. However, studying all three of these measures together may provide a more complete picture of nephron size than any alone.

Clinical characteristics can associate differently with nephron size and nephron number. In a relatively heathy population, obesity associates with larger nephrons but not with nephron number; lower GFR is not associated with nephron size but associates with lower nephron number, and family history of ESKD associates with both larger and fewer nephrons.2 Both nephron number and nephron size are important to study for the prediction of outcomes. Indeed, we recently found that both low nephron number for age and larger glomerular volume in donors predicted a GFR<45 ml/min per 1.73 m2 a decade after kidney donation.5

Disclosures

A.D. Rule reports serving as a scientific advisor or membership with the National Institute of Diabetes and Digestive and Kidney Diseases (CKD Biomarker Consortium External Expert Panel), JASN (Associate Editor), and Mayo Clinic Proceedings (Section Editor) and other interests/relationships with UpToDate. The remaining author has nothing to disclose.

Funding

None.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • See related letter to the editor, “Can Total Nephron Number Predict Progressive CKD after Radical Nephrectomy?” on page 517, and original article, “Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function,” in Vol. 31, Iss. 11, on pages 2642–2652.

  • Copyright © 2021 by the American Society of Nephrology

References

  1. ↵
    1. Seibel J,
    2. Rebibou J-M,
    3. Legendre M
    : Can total nephron number predict progressive CKD after radical nephrectomy? J Am Soc Nephrol 32: 517, 2021
    OpenUrlFREE Full Text
  2. ↵
    1. Denic A,
    2. Lieske JC,
    3. Chakkera HA,
    4. Poggio ED,
    5. Alexander MP,
    6. Singh P, et al
    .: The substantial loss of nephrons in healthy human kidneys with aging. J Am Soc Nephrol 28: 313–320, 2017pmid:27401688
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Denic A,
    2. Elsherbiny H,
    3. Mullan AF,
    4. Leibovich BC,
    5. Thompson RH,
    6. Ricaurte Archila L, et al
    .: Larger nephron size and nephrosclerosis predict progressive CKD and mortality after radical nephrectomy for tumor and independent of kidney function. J Am Soc Nephrol 31: 2642–2652, 2020pmid:32938650
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Denic A,
    2. Alexander MP,
    3. Kaushik V,
    4. Lerman LO,
    5. Lieske JC,
    6. Stegall MD, et al
    .: Detection and clinical patterns of nephron hypertrophy and nephrosclerosis among apparently healthy adults. Am J Kidney Dis 68: 58–67, 2016pmid:26857648
    OpenUrlPubMed
  5. ↵
    1. Merzkani MA,
    2. Denic A,
    3. Narasimhan R,
    4. Lopez CL,
    5. Larson JJ,
    6. Kremers WK, et al
    .: Kidney microstructural features at the time of donation predict long-term risk of chronic kidney disease in living kidney donors [published online ahead of print October 20, 2020]. Mayo Clin Proc 10.1016/j.mayocp.2020.08.0412020pmid:33097219
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 32 (2)
Journal of the American Society of Nephrology
Vol. 32, Issue 2
February 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Authors’ Reply
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Authors’ Reply
Aleksandar Denic, Andrew D. Rule
JASN Feb 2021, 32 (2) 517-518; DOI: 10.1681/ASN.2020111615

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Authors’ Reply
Aleksandar Denic, Andrew D. Rule
JASN Feb 2021, 32 (2) 517-518; DOI: 10.1681/ASN.2020111615
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Disclosures
    • Funding
    • Footnotes
    • References
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Authors' Reply
  • Remdesivir in COVID-19 Patients with Impaired Renal Function
Show more Letters to the Editor

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • Can Total Nephron Number Predict Progressive CKD after Radical Nephrectomy?
  • Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function
  • Google Scholar

Keywords

  • nephron
  • renal morphology
  • glomerulus

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire