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International Urology and Nephrology

, Volume 50, Issue 12, pp 2221–2228 | Cite as

Chronobiology in nephrology: the influence of circadian rhythms on renal handling of drugs and renal disease treatment

  • Lucas De Lavallaz
  • Carlos G. Musso
Nephrology - Review
  • 113 Downloads

Abstract

Introduction

Chronobiology studies the phenomenon of rhythmicity in living organisms. The circadian rhythms are genetically determined and regulated by external synchronizers (the daylight cycle). Several biological processes involved in the pharmacokinetics and pharmacodynamics of drugs are subjected to circadian variations. Chronopharmacology studies how biological rhythms influence pharmacokinetics, pharmacodynamics, and toxicity, and determines whether time-of-day administration modifies the pharmacological characteristics of the drug. Chronotherapy applies chronopharmacological studies to clinical treatments, determining the best biological time for dosing: when the beneficial effects are maximal and the incidence and/or intensity of related side effects and toxicity are minimal. Most water-soluble drugs or drug metabolites are eliminated by urine through the kidney. The rate of drug clearance in the urine depends on several intrinsic variables related to renal function including renal blood flow, glomerular filtration rate, the ability of the kidney to reabsorb or to secrete drugs, urine flow, and urine pH, which influences the degree of urine acidification. Curiously, all these variables present a circadian behavior in different mammalian models.

Conclusion

The circadian rhythms have influence in the renal physiology, pathophysiology, and pharmacology, and these data should be taken into account in clinical nephrology practice.

Keywords

Chronobiology Chronopharmacology Renal disease 

Notes

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflicts of interest.

References

  1. 1.
    Gumz ML (2016) Molecular basis of circadian rhythmicity in renal physiology and pathophysiology. Exp Physiol 101(8)1025–1029.  https://doi.org/10.1113/EP085781 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Gumz ML (2014) Tick tock: time to recognize the kidney clock. J Am Soc Nephrol 25(7):1369–1371.  https://doi.org/10.1681/ASN.2014020199 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Douma LG, Gumz ML (2018) Circadian clock-mediated regulation of blood pressure. Free Radic Biol Med 119:108–114.  https://doi.org/10.1016/j.freeradbiomed.2017.11.024 CrossRefPubMedGoogle Scholar
  4. 4.
    Solocinski K, Gumz ML (2015) The circadian clock in the regulation of renal rhythms. J Biol Rhythms 30(6):470–486.  https://doi.org/10.1177/0748730415610879 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Richards J, Gumz ML (2013) Mechanism of the circadian clock in physiology. Am J Physiol Regul Integr Comp Physiol 304(12):R1053–R1064.  https://doi.org/10.1152/ajpregu.00066.2013 CrossRefGoogle Scholar
  6. 6.
    Richards J, Gumz ML (2012) Advances in understanding the peripheral circadian clocks. FASEB J 26(9):3602–3613.  https://doi.org/10.1096/fj.12-203554 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pons M, Tranchot J, L’Azou B, Cambar J (1994) Circadian rhythms of renal hemodynamics in unanesthetized, unrestrained rats. Chronobiol Int 11(5):301–308CrossRefGoogle Scholar
  8. 8.
    Koren G, Ferrazzini G, Sohl H, Robieux I, Johnson D, Giesbrecht E (1992) Chronopharmacology of methotrexate pharmacokinetics in childhood leukemia. Chronobiol Int 9(6):434–438CrossRefGoogle Scholar
  9. 9.
    Stow LR, Gumz ML (2011) The circadian clock in the kidney. J Am Soc Nephrol 22(4):598–604.  https://doi.org/10.1681/ASN.2010080803 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gumz ML (2014) Molecular origin of the kidney clock. Kidney Int 86(5):873–874.  https://doi.org/10.1038/ki.2014.239 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wei N, Gumz ML, Layton AT (2018) Predicted effect of circadian clock modulation of NHE3 of a proximal tubule cell on sodium transport. Am J Physiol Renal Physiol.  https://doi.org/10.1152/ajprenal.00008.2018 CrossRefPubMedGoogle Scholar
  12. 12.
    Richards J, Cheng KY, All S, Skopis G, Jeffers L, Lynch IJ, Wingo CS, Gumz ML (2013) A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention. Am J Physiol Renal Physiol 305(12):F1697–F1704.  https://doi.org/10.1152/ajprenal.00472.2013 CrossRefGoogle Scholar
  13. 13.
    Richards J, Jeffers LA, All SC, Cheng KY, Gumz ML (2013) Role of Per1 and the mineralocorticoid receptor in the coordinate regulation of αENaC in renal cortical collecting duct cells. Front Physiol 4:253.  https://doi.org/10.3389/fphys.2013.00253 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Richards J, Greenlee MM, Jeffers LA, Cheng KY, Guo L, Eaton DC, Gumz ML (2012) Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε. Am J Physiol Renal Physiol 303(7):F918–F927.  https://doi.org/10.1152/ajprenal.00678.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Richards J, Ko B, All S, Cheng KY, Hoover RS, Gumz ML (2014) A role for the circadian clock protein Per1 in the regulation of the NaCl Co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells. J Biol Chem 289(17):11791–11806CrossRefGoogle Scholar
  16. 16.
    Richards J, Welch AK, Barilovits SJ, All S, Cheng KY, Wingo CS, Cain BD, Gumz ML (2014) Tissue-specific and time-dependent regulation of the endothelin axis by the circadian clockprotein Per1. Life Sci 118(2):255–262.  https://doi.org/10.1016/j.lfs.2014.03.028 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Solocinski K, Richards J, All S, Cheng KY, Khundmiri SJ, Gumz ML (2015) Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells. Am J Physiol Renal Physiol 309(11):F933–F942.  https://doi.org/10.1152/ajprenal.00197.2014 CrossRefGoogle Scholar
  18. 18.
    Richards J, Ko B, All S, Cheng KY, Hoover RS, Gumz ML (2014) A role for the circadian clock protein Per1 in the regulation of the NaCl co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells. J Biol Chem 289(17):11791–11806.  https://doi.org/10.1074/jbc.M113.531095 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Douma LG, Holzworth MR, Solocinski K, Masten SH, Miller AH, Cheng KY, Lynch IJ, Cain BD, Wingo CS, Gumz ML (2018) Renal Na-handling defect associated with PER1-dependent nondipping hypertension in male mice. Am J Physiol Renal Physiol 314(6):F1138–F1144.  https://doi.org/10.1152/ajprenal.00546.2017 CrossRefPubMedGoogle Scholar
  20. 20.
    Solocinski K, Holzworth M, Wen X, Cheng KY, Lynch IJ, Cain BD, Wingo CS, Gumz ML (2017) Desoxycorticosterone pivalate-salt treatment leads to non-dipping hypertension in Per1 knockout mice. Acta Physiol (Oxford) 220(1):72–82.  https://doi.org/10.1111/apha.12804 CrossRefGoogle Scholar
  21. 21.
    Gumz ML, Cheng KY, Lynch IJ, Stow LR, Greenlee MM, Cain BD, Wingo CS (2010) Regulation of αENaC expression by the circadian clock protein Period 1 in mpkCCD(c14) cells. Biochim Biophys Acta 1799(9):622–629.  https://doi.org/10.1016/j.bbagrm.2010.09.003 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Gumz ML, Stow LR, Lynch IJ, Greenlee MM, Rudin A, Cain BD, Weaver DR, Wingo CS (2009) The circadian clock protein period 1 regulates expression of the renal epithelial sodium channel in mice. J Clin Invest 119(8):2423–2434.  https://doi.org/10.1172/JCI36908 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Richards J, All S, Skopis G, Cheng KY, Compton B, Srialluri N, Stow L, Jeffers LA, Gumz ML (2013) Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney. Am J Physiol Regul Integr Comp Physiol 305(7):R735–R747.  https://doi.org/10.1152/ajpregu.00195.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Gumz ML, Rabinowitz L (2013) Role of circadian rhythms in potassium homeostasis. Semin Nephrol 33(3):229–236.  https://doi.org/10.1016/j.semnephrol.2013.04.003 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bouchlariotou S, Liakopoulos V, Giannopoulou M, Arampatzis S, Eleftheriadis T, Mertens PR, Zintzaras E, Messinis IE, Stefanidis I (2014) Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm. Renal Fail 36(7):1001–1007.  https://doi.org/10.3109/0886022X.2014.926216 CrossRefGoogle Scholar
  26. 26.
    Richards J, Diaz AN, Gumz ML (2014) Clock genes in hypertension: novel insights from rodent models. Blood Press Monit 19(5):249–254.  https://doi.org/10.1097/MBP.0000000000000060 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Stow LR, Richards J, Cheng KY, Lynch IJ, Jeffers LA, Greenlee MM, Cain BD, Wingo CS, Gumz ML (2012) The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes. Hypertension 59(6):1151–1156.  https://doi.org/10.1161/HYPERTENSIONAHA.112.190892 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fezeu L, Bankir L, Hansel B, Guerrot D (2014) Differential circadian pattern of water and Na excretion rates in the metabolic syndrome. Chronobiol Int 31(7):861–867.  https://doi.org/10.3109/07420528.2014.917090 CrossRefPubMedGoogle Scholar
  29. 29.
    Liangpunsakul S, Agarwal R (2017) Altered circadian hemodynamic and renal function in cirrhosis. Nephrol Dial Transplant 32(2):333–342PubMedGoogle Scholar
  30. 30.
    Bonny O, Vinciguerra M, Gumz ML, Mazzoccoli G (2013) Molecular bases of circadian rhythmicity in renal physiology and pathology. Nephrol Dial Transplant 28(10):2421–2431.  https://doi.org/10.1093/ndt/gft319 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Xu H, Huang X, Risérus U, Cederholm T, Sjögren P, Lindholm B, Ärnlöv J, Carrero JJ (2015) Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study. Clin Kidney J 8(5):560–566.  https://doi.org/10.1093/ckj/sfv068 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hermida RC, Smolensky MH, Ayala DE, Portaluppi F (2015) Ambulatory blood pressure monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults. Chronobiol Int 32(10):1329–1342CrossRefGoogle Scholar
  33. 33.
    Hermida RC, Ayala DE, Smolensky MH, Fernández JR, Mojón A, Portaluppi F (2017) Sleep-time blood pressure: unique sensitive prognostic marker of vascular risk and therapeutic target for prevention. Sleep Med Rev 33:17–27CrossRefGoogle Scholar
  34. 34.
    Hermida RC (2016) Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: rationale and design of the Hygia Project. Chronobiol Int 33(7):906–936CrossRefGoogle Scholar
  35. 35.
    Sallam H, El-Serafi AT, Filipski E, Terelius Y, Lévi F, Hassan M (2015) The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk inhibitor, roscovitine, in tumor mice model. Chronobiol Int 32(5):608–614CrossRefGoogle Scholar
  36. 36.
    Liu Y, Ushijima K, Ohmori M, Takada M, Tateishi M, Ando H, Fujimura A (2011) Chronopharmacology of angiotensin II-receptor blockers in stroke-prone spontaneously hypertensive rats. J Pharmacol Sci 115(2):196–204CrossRefGoogle Scholar
  37. 37.
    Fujimura A, Kajiyama H, Ohashi K, Ebihara A (1991) Chronopharmacology of the new uricosuric diuretic S-8666 in rats: (II). Examination in aged rats. Jpn J Pharmacol 56(1):43–51CrossRefGoogle Scholar
  38. 38.
    Fujimura A, Shiga T, Sudoh T, Ohashi K, Ebihara A (1992) Influence of renal denervation on chronopharmacology of furosemide in rats. Life Sci 51(23):1811–1816CrossRefGoogle Scholar
  39. 39.
    Fujimura A, Shiga T, Ohashi K, Ebihara A (1992) Chronopharmacology of furosemide in rats with amikacin-induced acute renal damage. Jpn J Pharmacol 60(3):153–157CrossRefGoogle Scholar
  40. 40.
    Rebuelto M (2006) Chronopharmacology and antimicrobial therapeutics. Curr Clin Pharmacol 1(3):265–275CrossRefGoogle Scholar
  41. 41.
    Blunston MA, Yonovitz A, Woodahl EL, Smolensky MH (2015) Gentamicin-induced ototoxicity and nephrotoxicity vary with circadian time of treatment and entail separate mechanisms. Chronobiol Int 32(9):1223–1232CrossRefGoogle Scholar
  42. 42.
    Dridi I, Ben-Cherif W, Chahdoura H, Haouas Z, Ben-Attia M, Aouam K, Reinberg A, Boughattas NA (2017) Dosing-time dependent oxidative effects of an immunosuppressive drug “Mycophenolate Mofetil” on rat kidneys. Biomed Pharmacother 87:509–518CrossRefGoogle Scholar
  43. 43.
    Burkhalter H, De Geest S, Wirz-Justice A, Cajochen C (2016) Melatonin rhythms in renal transplant recipients with sleep-wake disturbances. Chronobiol Int 33(7):810–820CrossRefGoogle Scholar
  44. 44.
    Vinod C, Jagota A (2016) Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin. Biogerontology 17(5–6):859–871CrossRefGoogle Scholar
  45. 45.
    Vinod C, Jagota A (2017) Daily Socs1 rhythms alter with aging differentially in peripheral clocks in male Wistar rats: therapeutic effects of melatonin. Biogerontology 18(3):333–345CrossRefGoogle Scholar
  46. 46.
    Correa-Costa M, Gallo D, Csizmadia E, Gomperts E, Lieberum J-L, Hauser CJ, Ji X, Wang B, Câmara NOS, Robson SC, Otterbein LE (2018) Carbon monoxide protects the kidney through the central circadian clock and CD39. Proc Natl Acad Sci USA 115(10):E2302–E2310CrossRefGoogle Scholar
  47. 47.
    Eckle T, Hartmann K, Bonney S, Reithel S, Mittelbronn M, Walker LA, Lowes BD, Han J, Borchers CH, Buttrick PM, Kominsky DJ, Colgan SP, Eltzschig HK (2012) Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch critical for myocardial adaptation to ischemia. Nat Med 18(5):774–782CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Human Physiology DepartmentInstituto Universitario del Hospital Italiano de Buenos AiresBuenos AiresArgentina

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