Skip to main content
Log in

How kidney clock works: circadian pattern of eGFR based on a population data group

  • Original Article
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript


A circadian regulation of renal function it has been described in the last few years. An intradaily variation in glomerular filtration rate (eGFR) has also been discovered at the individual level. The aim of this study was to check if there exists a circadian pattern of eGFR at population data group level and to compare the population results with those described at individual level. We have studied a total of 446,441 samples analysed in the emergency laboratories of two Spanish hospitals between January 2015 and December 2019. We selected all the records of eGFR values between 60 and 140 mL/min/1.73 m2 using CKD-EPI formula from patients between 18 and 85 years. The intradaily intrinsic eGFR pattern was computed using the extraction time of day in four nested mixed linear and sinusoidal regression models. All models showed an intradaily eGFR pattern, but the estimated model coefficients differed depending on whether age was included. The inclusion of age improved the performance of the model. In this model, the acrophase occurred at 7:46 h. We describe the distribution of eGFR values depending on the time in two different populations. This distribution is adjusted to a circadian rhythm that behaves similarly to the individual rhythm. This pattern is similar in each of the years studied from each hospital as well as between both hospitals. The results found suggest the incorporation of the concept of “population circadian rhythm” into the scientific world.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Abou El Hassan M, Delvin E, Elnenaei MO, Hoffman B (2018) Diurnal rhythm in clinical chemistry: an underrated source of variation. Crit Rev Clin Lab Sci 55:516–534

    Article  Google Scholar 

  2. Buijsen JG, van Acker BA, Koomen GC, Koopman MG, Arisz L (1994) Circadian rhythm of glomerular filtration rate in patients after kidney transplantation. Nephrol Dial Transplant 9:1330–1333

    CAS  PubMed  Google Scholar 

  3. De Lavallaz L, Musso CG (2018) Chronobiology in nephrology: the influence of circadian rhythms on renal handling of drugs and renal disease treatment. Int Urol Nephrol 50:2221–2228

    Article  PubMed  Google Scholar 

  4. de Redactores G, Martínez-Castelao A, Górriz-Teruel JL, Bover-Sanjuán J, Segura-de la Morena J, Cebollada J, Escalada J et al (2014) Consensus document for the detection and management of chronic kidney disease. Nefrología (English Edition) 34:243–262

    Google Scholar 

  5. Firsov D, Bonny O (2010) Circadian regulation of renal function. Kidney Int 78:640–645

    Article  PubMed  Google Scholar 

  6. Firsov D, Bonny O (2018) Circadian rhythms and the kidney. Nat Rev Nephrol 14:626–635

    Article  CAS  PubMed  Google Scholar 

  7. Haus E, Touitou Y (1992) Chronobiology in laboratory medicine. In: Touitou Y et al (eds) Biologic rhythms in clinical and laboratory medicine. Springer-Verlag, Berlin Heidelberg, pp 673–708

    Chapter  Google Scholar 

  8. Hilderink JM, van der Linden N, Kimenai DM, Litjens EJR, Klinkenberg LJJ, Aref BM, Aziz F et al (2018) Biological variation of creatinine, cystatin C, and eGFR over 24 hours. Clin Chem 64:851–860

    Article  CAS  PubMed  Google Scholar 

  9. Inker LA, Schmid CH, Tighiouart H et al (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jacquelin J., Régressions Et 2014 Équations Intégrales, Online resource .

  11. Johnston JG, Pollock DM (2018) Circadian regulation of renal function. Free Radic Biol Med 119:93–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Koopman MG, Koomen GC, Krediet RT, de Moor EA, Hoek FJ, Arisz L (1989) Circadian rhythm of glomerular filtration rate in normal individuals. Clin Sci (Lond) 77:105–111

    Article  CAS  PubMed  Google Scholar 

  13. Larsson A, Akerstedt T, Hansson LO, Axelsson J (2008) Circadian variability of cystatin C, creatinine, and glomerular filtration rate (GFR) in healthy men during normal sleep and after an acute shift of sleep. Chronobiol Int 25:1047–1061

    Article  CAS  PubMed  Google Scholar 

  14. Madsen AT, Hojbjerg JA, Sorensen BS, Winther-Larsen A (2019) Day-to-day and within-day biological variation of cell-free DNA. EBioMedicine 49:284–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. McKeigue PM, Reynard JM (2000) Relation of nocturnal polyuria of the elderly to essential hypertension. Lancet 355(9202):486–488

    Article  CAS  PubMed  Google Scholar 

  16. Ravn B, Larsson A, Mårtensson J, Martling CR, Bell M (2016) Intra-day variability of cystatin C, creatinine and estimated GFR in intensive care patients. Clin Chim Acta 460:1–4

    Article  CAS  PubMed  Google Scholar 

  17. Reilly RF, Jackson EK (2011) Regulation of renal function and vascular volume. In: Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New York, pp 671–719

    Google Scholar 

  18. Rivara MB, Zelnick LR, Hoofnagle AN, Newitt R, Tracy RP, Kratz M, Weigle DS, Kestenbaum BR (2017) Diurnal and long-term variation in plasma concentrations and renal clearances of circulating markers of kidney proximal tubular secretion. Clin Chem 63:915–923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Silveiro S, Zelmanovitz T (2018) Does twenty-four-hour biological variation of serum creatinine and cystatin C influence GFR estimation? [Editorial]. J Lab Precis Med 3:65

    Article  Google Scholar 

  20. Tolan NV, Parnas ML, Baudhuin LM, Cervinski MA, Chan AS, Holmes DT, Horowitz G et al (2015) “Big Data” in laboratory medicine. Clin Chem 61:1433–1440

    Article  CAS  PubMed  Google Scholar 

  21. Van Cauter E (1990) Diurnal and ultradian rhythms in human endocrine function: a minireview. Horm Res 34:45–53

    Article  PubMed  Google Scholar 

  22. Voogel AJ, Koopman MG, Hart AA, van Montfrans GA, Arisz L (2001) Circadian rhythms in systemic hemodynamics and renal function in healthy subjects and patients with nephrotic syndrome. Kidney Int 59:1873–1880

    Article  CAS  PubMed  Google Scholar 

  23. Webster AC, Nagler EV, Morton RL, Masson P (2017) Chronic kidney disease. Lancet 389:1238–1252

    Article  PubMed  Google Scholar 

  24. Wuerzner G, Firsov D, Bonny O (2014) Circadian glomerular function: from physiology to molecular and therapeutical aspects. Nephrol Dial Transplant 29:1475–1480

    Article  PubMed  Google Scholar 

  25. Zhang D, Pollock DM (2018) Circadian regulation of kidney function: finding a role for Bmal1. Am J Physiol Renal Physiol 314:F675–F678

    Article  CAS  PubMed  Google Scholar 

  26. Zhang Z (2017) The role of big-data in clinical studies in laboratory medicine. J Lab Precis Med 2:34

    Article  Google Scholar 

Download references


We thank Dr. Francisco Jose García García (Toledo Study of Healthy Aging. CIBERFES (ISCIII)) for introducing the authors of the study and listening to our ideas. We thank to the Spanish Research Group in Biological Rhythms and Laboratory Medicine for being the link to carry out the study.

Author information

Authors and Affiliations



Lorenzo-Lozano, Blázquez-Manzanera and Carnicero have contributed equally as first authors. The authors declare that all data were generated in-house.

Corresponding author

Correspondence to MC. Lorenzo-Lozano.

Ethics declarations

Ethics approval and consent to participate

The study has been approved by the Ethics Committee for Clinical Research with Medicines of the University Hospital of Toledo with registration number 948. The study presented was performed with the Standards of Good Clinical Practice, the fundamental ethical principles established in the 1964 Declaration of Helsinki and its later amendments, the Oviedo Convention, as well as the requirements established in Spanish legislation.

Informed consent

Not applicable.

Competing interests

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.

Key points

• There is a circadian rhythm in the laboratory values analysed from a population data set.

• A disadvantage of chronobiology is the collection of individual 24-h data.

• Studying circadian patterns at the population level is a major step in chronobiology.

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

Lorenzo-Lozano, M., Blázquez-Manzanera, A. & Carnicero, J. How kidney clock works: circadian pattern of eGFR based on a population data group. J Physiol Biochem 79, 543–554 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: