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.

  • Article
  • Published:

Definition of hyperfiltration taking into account age-related decline in renal function in kidney donor candidates with obesity and glucose tolerance disorder

Hypertension Research volume 48, pages 1115–1124 (2025)Cite this article

A Comment to this article was published on 16 January 2025

Abstract

The definition of hyperfiltration, the main pathogenesis in renal impairment in obesity and diabetes mellitus, is uncertain. Glomerular filtration rate (GFR) declines physiologically with aging, and there is inaccuracy in GFR in obesity due to body surface area (BSA) correction. Here, we defined hyperfiltration using GFR without BSA correction, but with inclusion of aging, and investigated hyperfiltration using this definition and absolute GFR > 125 mL/min. The subjects were 180 kidney donor candidates (56.4 ± 11.3 years old, 79 males). GFR was evaluated using inulin clearance. A two-hour 75-g oral glucose tolerance test was also performed. The subjects were divided into four groups with and without a combination of glucose tolerance disorder and BMI. Normal glucose tolerance (NGT) and BMI < 25 kg/m2 were defined as normal, and hyperfiltration was defined as the upper 95% confidence interval of the relationship of aging and GFR in normal cases, and compared with GFR > 125 mL/min. RESULTS: GFR without BSA correction and UAE in non-NGT subjects with obesity were higher than in other groups, but GFR with BSA correction did not show this relationship. In multiple regression analysis, BMI was independently associated with GFR without BSA correction, but not with BSA correction. Aging was consistently associated with GFR. The prevalence of hyperfiltration by our definition (GFR = −0.883 × Age + 167.398) was significantly higher than that using GFR > 125 mL/min (P < 0.0001). Hyperfiltration in obesity and/or glucose tolerance disorder should be evaluated using GFR without BSA correction and including the decline of GFR due to aging.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH, et al. Diabetic nephropathy. Diabetes Care. 2003;26:S94–8.

    Article  PubMed  Google Scholar 

  2. Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020;43:487–93.

    Article  CAS  PubMed  Google Scholar 

  3. Cardoso CRL, Leite NC, Salles GC, Ferreira MT, Salles GF. Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetologia 2018;61:455–65.

    Article  CAS  PubMed  Google Scholar 

  4. Araki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, et al. Japanese Clinical Practice Guideline for Diabetes 2019. J Diabetes Investig. 2020;11:1020–76.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ. The clinical significance of hyperfiltration in diabetes. Diabetologia 2010;53:2093–104.

    Article  CAS  PubMed  Google Scholar 

  6. Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, et al. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012;35:2061–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Peti-Peterdi J, Kang JJ, Toma I. Activation of the renal renin-angiotensin system in diabetes-new concepts. Nephrol Dial Transpl. 2008;23:3047–9.

    Article  Google Scholar 

  8. Chagnac A, Weinstein T, Korzets A, Ramadan E, Hirsch J, Gafter U. Glomerular hemodynamics in severe obesity. Am J Physiol Ren Physiol. 2000;278:F817–22.

    Article  CAS  Google Scholar 

  9. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 2002;51:536–40.

    Article  CAS  PubMed  Google Scholar 

  10. Tsuda A, Ishimura E, Uedono H, Ochi A, Nakatani S, Morioka T, et al. Association of Albuminuria With Intraglomerular Hydrostatic Pressure and Insulin Resistance in Subjects With Impaired Fasting Glucose and/or Impaired Glucose Tolerance. Diabetes Care. 2018;41:2414–20.

    Article  CAS  PubMed  Google Scholar 

  11. Cortinovis M, Perico N, Ruggenenti P, Remuzzi A, Remuzzi G. Glomerular hyperfiltration. Nat Rev Nephrol. 2022;18:435–51.

    Article  PubMed  Google Scholar 

  12. Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, et al. The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. J Am Soc Nephrol. 2017;28:313–20.

    Article  PubMed  Google Scholar 

  13. Levey AS, Kramer H. Obesity, glomerular hyperfiltration, and the surface area correction. Am J Kidney Dis. 2010;56:255–8.

    Article  PubMed  Google Scholar 

  14. Ethics Committee of the Transplantation S. The consensus statement of the Amsterdam Forum on the Care of the Live Kidney Donor. Transplantation 2004;78:491–2.

    Article  Google Scholar 

  15. Takahashi H, Mori M. [Characteristics and significance of criteria for obesity disease in Japan 2011]. Nihon Rinsho. 2013;71:257–61.

    PubMed  Google Scholar 

  16. Horio M, Imai E, Yasuda Y, Hishida A, Matsuo S. Simple sampling strategy for measuring inulin renal clearance. Clin Exp Nephrol. 2009;13:50–4.

    Article  CAS  PubMed  Google Scholar 

  17. Tsuda A, Inaba M, Ichii M, Ochi A, Ohno Y, Nakatani S, et al. Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects. Eur J Endocrinol. 2013;169:45–50.

    Article  CAS  PubMed  Google Scholar 

  18. Tsuda A, Ishimura E, Ohno Y, Ichii M, Nakatani S, Mori K, et al. Significant association of poor glycemic control with increased resistance in efferent arterioles-study of inulin and para-aminohippuric acid clearance in humans. Diabetes Res Clin Pr. 2014;104:234–40.

    Article  CAS  Google Scholar 

  19. Tsuda A, Ishimura E, Ohno Y, Ichii M, Nakatani S, Machida Y, et al. Poor glycemic control is a major factor in the overestimation of glomerular filtration rate in diabetic patients. Diabetes Care. 2013. e-pub ahead of print 2013/10/17doi:dc13-1899 [pii]10.2337/dc13-1899)

  20. Fliser D, Dikow R, Demukaj S, Ritz E. Opposing effects of angiotensin II on muscle and renal blood flow under euglycemic conditions. J Am Soc Nephrol: JASN. 2000;11:2001–6.

    Article  CAS  PubMed  Google Scholar 

  21. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, et al. Sclerostin and insulin resistance in prediabetes: evidence of a cross talk between bone and glucose metabolism. Diabetes Care. 2015;38:1509–17.

    Article  CAS  PubMed  Google Scholar 

  22. American Diabetes A. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37:S14–80.

    Article  Google Scholar 

  23. Sun ZJ, Yang YC, Wu JS, Wang MC, Chang CJ, Lu FH. Increased risk of glomerular hyperfiltration in subjects with impaired glucose tolerance and newly diagnosed diabetes. Nephrol Dial Transpl. 2016;31:1295–301.

    Article  CAS  Google Scholar 

  24. Berg UB. Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors. Nephrol Dial Transpl. 2006;21:2577–82.

    Article  CAS  Google Scholar 

  25. Delanaye P, Radermecker RP, Rorive M, Depas G, Krzesinski JM. Indexing glomerular filtration rate for body surface area in obese patients is misleading: concept and example. Nephrol Dial Transpl. 2005;20:2024–8.

    Article  Google Scholar 

  26. Hommos MS, Glassock RJ, Rule AD. Structural and functional changes in human kidneys with healthy aging. J Am Soc Nephrol. 2017;28:2838–44.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hall JE. Guyton & hall physiology review. (e-pub ahead of print 4. Published 4.). 4. edn. Elsevier, Inc: Philadelphia, 2020.

  28. Rule AD, Amer H, Cornell LD, Taler SJ, Cosio FG, Kremers WK, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010;152:561–7.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schlaich MP, Schmitt D, Ott C, Schmidt BMW, Schmieder RE. Basal nitric oxide synthase activity is a major determinant of glomerular haemodynamics in humans. J Hypertens. 2008;26:110–6.

    Article  CAS  PubMed  Google Scholar 

  30. Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009;301:2129–40.

    Article  CAS  PubMed  Google Scholar 

  31. Kiya M, Tamura Y, Takeno K, Someya Y, Kakehi S, Sato M, et al. Adipose insulin resistance and decreased adiponectin are correlated with metabolic abnormalities in nonobese men. J Clin Endocrinol Metab. 2021;106:e2228–e38.

    Article  PubMed  Google Scholar 

  32. Tomiyama H, Vlachopoulos C, Xaplanteris P, Nakano H, Shiina K, Ishizu T, et al. Usefulness of the SAGE score to predict elevated values of brachial-ankle pulse wave velocity in Japanese subjects with hypertension. Hypertens Res. 2020;43:1284–92.

    Article  PubMed  Google Scholar 

  33. Bohlen HG. Nitric oxide and the cardiovascular system. Compr Physiol. 2015;5:808–23.

    PubMed  Google Scholar 

  34. Horio M, Yasuda Y, Kaimori J, Ichimaru N, Isaka Y, Takahara S, et al. Performance of the Japanese GFR equation in potential kidney donors. Clin Exp Nephrol. 2012;16:415–20.

    Article  CAS  PubMed  Google Scholar 

  35. Tsuda A, Ishimura E, Ohno Y, Ichii M, Nakatani S, Machida Y, et al. Poor glycemic control is a major factor in the overestimation of glomerular filtration rate in diabetic patients. Diabetes Care. 2014;37:596–603.

    Article  CAS  PubMed  Google Scholar 

  36. De Cosmo S, Menzaghi C, Prudente S, Trischitta V. Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence. Nephrol Dial Transpl. 2013;28:29–36.

    Article  Google Scholar 

  37. Ozarda Y, Sikaris K, Streichert T, Macri J, intervals ICoR, Decision L. Distinguishing reference intervals and clinical decision limits - A review by the IFCC Committee on Reference Intervals and Decision Limits. Crit Rev Clin Lab Sci. 2018;55:420–31.

    Article  CAS  PubMed  Google Scholar 

Download references

Source of funding

This study was not funded by a grant from a funding agency in the public, commercial or not-for-profit sector.

Author information

Authors and Affiliations

  1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Akihiro Tsuda, Hideki Uedono, Shinya Nakatani, Masafumi Kurajoh, Shinsuke Yamada, Tomoaki Morioka & Masanori Emoto

  2. Department of Nephrology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Katsuhito Mori, Eiji Ishimura & Masanori Emoto

  3. Department of Vascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Yuki Nagata

  4. Department of Nephrology, Meijibashi Hospital, Matsubara, Osaka, Japan

    Eiji Ishimura

  5. Department of Urology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Junji Uchida

Authors
  1. Akihiro Tsuda
    View author publications

    Search author on:PubMed Google Scholar

  2. Katsuhito Mori
    View author publications

    Search author on:PubMed Google Scholar

  3. Hideki Uedono
    View author publications

    Search author on:PubMed Google Scholar

  4. Shinya Nakatani
    View author publications

    Search author on:PubMed Google Scholar

  5. Yuki Nagata
    View author publications

    Search author on:PubMed Google Scholar

  6. Masafumi Kurajoh
    View author publications

    Search author on:PubMed Google Scholar

  7. Shinsuke Yamada
    View author publications

    Search author on:PubMed Google Scholar

  8. Tomoaki Morioka
    View author publications

    Search author on:PubMed Google Scholar

  9. Eiji Ishimura
    View author publications

    Search author on:PubMed Google Scholar

  10. Junji Uchida
    View author publications

    Search author on:PubMed Google Scholar

  11. Masanori Emoto
    View author publications

    Search author on:PubMed Google Scholar

Contributions

AT and EI acquired the data and wrote the manuscript. AT, KM, HU, SN, YN, MK, SY, TM, JU, and ME contributed to the discussion and reviewed the manuscript. AT had full access to all study data and took responsibility for the integrity of the data and accuracy of the data analysis.

Corresponding author

Correspondence to Akihiro Tsuda.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsuda, A., Mori, K., Uedono, H. et al. Definition of hyperfiltration taking into account age-related decline in renal function in kidney donor candidates with obesity and glucose tolerance disorder. Hypertens Res 48, 1115–1124 (2025). https://doi.org/10.1038/s41440-024-02020-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41440-024-02020-y

Keywords

This article is cited by

Search

Advanced search

Quick links