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Biopsy-based estimation of total nephron number in Japanese living kidney donors

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Abstract

Background

Increasing evidence suggests that individuals with low nephron number have an increased lifetime risk of renal insufficiency, thereby emphasizing the importance of evaluating total nephron number in each individual. In recent years, new methods have been described for estimating human total nephron number using a combination of image analysis and renal biopsy, though the reproducibility and accuracy of these methods remain uncertain. This study estimated total nephron number in healthy Japanese subjects using such a method.

Methods

Implantation biopsies from 44 living kidney donors were analyzed. Using pre-donation contrast CT angiograms, transplantation donor kidneys were three-dimensionally reconstructed, and total renal cortical volume was estimated. Total nephron number was estimated based on glomerular density in biopsy specimens and total renal cortical volume. The obtained results were analyzed in relation to clinical variables and compared with those of a previously reported Japanese autopsy study.

Results

The estimated non-sclerotic and total numbers of glomeruli in this cohort were 650,000 ± 220,000 and 710,000 ± 220,000 (mean ± SD) per kidney. Non-sclerotic glomerular number ranged from 280,000 to 1,220,000 per kidney (4.4-fold) and correlated directly with eGFR (r = 0.328, p = 0.030) and inversely with age (r = − 0.355, p = 0.018).

Conclusion

The estimated total nephron number obtained in the present study was 25% less than that reported in American living kidney donors obtained using the same procedure and similar to that obtained in a previous Japanese autopsy study using the disector/fractionator method. These results confirm the feasibility of a combined CT angiography and biopsy-based method to estimate total nephron number in humans.

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Acknowledgements

This work was supported by the Japan Kidney Foundation Research Grant and JSPS KAKENHI Grant numbers JP25461236 and JP16K0936 (to NT). Parts of this study were presented at the 55th ERA-EDTA Congress, May 2018, Copenhagen, Denmark and the 61st Annual Meeting for the Japanese Society of Nephrology, June 2018, Niigata, Japan.

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, Japan

    Takaya Sasaki, Nobuo Tsuboi, Go Kanzaki, Kotaro Haruhara, Yusuke Okabayashi, Kentaro Koike, Akimitsu Kobayashi, Izumi Yamamoto, Makoto Ogura & Takashi Yokoo

  2. Centre for Chronic Disease, The University of Queensland, Brisbane, Australia

    Wendy E. Hoy

  3. Department of Anatomy and Developmental Biology and Biomedical Discovery Institute, Monash University, Melbourne, Australia

    John F. Bertram

  4. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan

    Akira Shimizu

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  1. Takaya Sasaki
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Corresponding author

Correspondence to Nobuo Tsuboi.

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Conflict of interest

The authors declare no conflicts of interest in association with the present study.

Human and animal rights

All procedures performed in the present study involving human participants were in accordance with the ethical standards of the Institutional Review Board of The Jikei University School of Medicine (IRB Approval No. 30–060, 9081) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Since the present study is a retrospective cross-sectional study using only past clinical data, it does not involve invasion or intervention. Therefore, document or verbal consent from each study subject is not required. In accordance with “Ethical guidelines for medical and health research involving human subjects (the Ministry of Education, Culture, Sports, Science and Technology/the Ministry of Health, Labour and Welfare in Japan, revised in 2017)”, by posting documents at conspicuous places in the hospital, we notified study subjects of study content so that they could easily understand it, and guaranteed opportunities for them to refuse it (opt out). If there was an offer that they would not want to be a subject of the study, we quickly excluded the subject’s data from the analysis and did not use their clinical information in this study.

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Sasaki, T., Tsuboi, N., Kanzaki, G. et al. Biopsy-based estimation of total nephron number in Japanese living kidney donors. Clin Exp Nephrol 23, 629–637 (2019). https://doi.org/10.1007/s10157-018-01686-2

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