Skip to main content
SpringerLink
Log in

Kidney–Brain Crosstalk in Acute Kidney Injury

  • Chapter
  • First Online:
Organ Crosstalk in Acute Kidney Injury

  • 227 Accesses

Abstract

Acute kidney injury can lead to neurological disorders caused by uremic toxin accumulation, electrolyte imbalance, drug toxicity, cytokines release, or/and dialytic negative effects. The subsequent disruption of the blood–brain barrier is an essential damage mechanism that leads to brain edema, drug toxicity, and impaired molecule trafficking due to the loss of normal transport channels. On the other hand, acute brain injury can generate direct renal damage by inducing neurohumoral changes, oxidative stress, and inflammation.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Afsar B, Sag AA, Yalcin CE, Kaya E, Siriopol D, Goldsmith D, Covic A, Kanbay M. Brain-kidney cross-talk: definition and emerging evidence. Eur J Intern Med. 2016;36:7–12.

    Article  PubMed  Google Scholar 

  2. Nongnuch A, Panorchan K, Davenport A. Brain–kidney crosstalk. Crit Care. 2014;18:1–11. Accessed 15 Jul 2021.

    Article  Google Scholar 

  3. Liu M, Liang Y, Chigurupati S, Lathia JD, Pletnikov M, Sun Z, Crow M, Ross CA, Mattson MP, Hamid R. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol. 2008;19:1360–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grisk O. The sympathetic nervous system in acute kidney injury. Acta Physiol. 2020;228:e13404.

    Article  CAS  Google Scholar 

  5. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988;12:123–37.

    Article  CAS  PubMed  Google Scholar 

  6. Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007;2:153–60.

    Article  Google Scholar 

  7. Civiletti F, Assenzio B, Mazzeo AT, Medica D, Giaretta F, Deambrosis I, Fanelli V, Ranieri VM, Cantaluppi V, Mascia L. Acute tubular injury is associated with severe traumatic brain injury: in vitro study on human tubular epithelial cells. Sci Rep. 2019;9:6090.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Morganti-Kossmann MC, Kossmann T, Wahl SM. Cytokines and neuropathology. Trends Pharmacol Sci. 1992;13:286–91.

    Article  CAS  PubMed  Google Scholar 

  9. Davenport A. Management of acute kidney injury in neurotrauma. Hemodial Int. 2010;14:27–31.

    Article  Google Scholar 

  10. Kovalčíková A, Gyurászová M, Vavrincová-Yaghi D, Vavrinec P, Tóthová L, Boor P, Šebeková K, Celec P. Oxidative stress in the brain caused by acute kidney injury. Metab Brain Dis. 2018;33:961–7.

    Article  PubMed  Google Scholar 

  11. Li X, Hassoun HT, Santora R, Rabb H. Organ crosstalk: the role of the kidney. Curr Opin Crit Care. 2009;15:481–7.

    Article  PubMed  Google Scholar 

  12. Lu R, Kiernan MC, Murray A, Rosner MH, Ronco C. Kidney-brain crosstalk in the acute and chronic setting. Nat Rev Nephrol. 2015;11:707–19.

    Article  CAS  PubMed  Google Scholar 

  13. Schneider R, Sauvant C, Betz B, Otremba M, Fischer D, Holzinger H, Wanner C, Galle J, Gekle M. Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats. Am J Physiol Renal Physiol. 2007;292:1599–605.

    Article  Google Scholar 

  14. Risso MA, Sallustio S, Sueiro V, Bertoni V, Gonzalez-Torres H, Musso CG. The importance of tubular function in chronic kidney disease. Int J Nephrol Renov Dis. 2019;12:257–62.

    Article  CAS  Google Scholar 

  15. Trinh-Trang-Tan MM, Cartron JP, Bankir L. Molecular basis for the dialysis disequilibrium syndrome: altered aquaporin and urea transporter expression in the brain. Nephrol Dial Transplant. 2005;20:1984–8.

    Article  CAS  PubMed  Google Scholar 

  16. Burn DJ, Bates D. Neurology and the kidney. J Neurol Neurosurg Psychiatry. 1998;65:810–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Davenport A. Renal replacement therapy for the patient with acute traumatic brain injury and severe acute kidney injury. Contrib Nephrol. 2007;156:333–9.

    Article  PubMed  Google Scholar 

  18. Hooge RD, Peib YQ, Marescau B, De Deyn PP. Convulsive action and toxicity of uremic guanidino compounds: behavioral assessment and relation to brain concentration in adult mice. J Neurol Sci. 1992;112:96–105.

    Article  PubMed  Google Scholar 

  19. Glorieux GL, Dhondt AW, Jacobs P, Van Langeraert B, Lameire NH, De Deyn PP, Vanholder RC. In vitro study of the potential role of guanidines in leukocyte functions related to atherogenesis and infection. Kidney Int. 2004;65:2184–92.

    Article  CAS  PubMed  Google Scholar 

  20. Leong SC, Sirich TL. Indoxyl sulfate-review of toxicity and therapeutic strategies. Toxins. 2016;8:1–13.

    Article  Google Scholar 

  21. Van Dijck A, Van Daele W, De Deyn PP. Uremic encephalopathy. Miscellanea on encephalopathies—a second look. InTech; 2021. p. 23–38.

    Google Scholar 

  22. Zha XM. Acid-sensing ion channels: trafficking and synaptic function. Mol Brain. 2013;6:13.

    Article  Google Scholar 

  23. Samways DSK, Harkins AB, Egan TM. Native and recombinant ASIC1a receptors conduct negligible Ca2+ entry. Cell Calcium. 2009;45:319–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vanholder R, Van Landschoot N, De Smet R, Schoots A, Ringoir S. Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney Int. 1988;33:996–1004.

    Article  CAS  PubMed  Google Scholar 

  25. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.

    Article  PubMed  PubMed Central  Google Scholar 

  26. McKenna MC. Glutamate dehydrogenase in brain mitochondria: do lipid modifications and transient metabolon formation influence enzyme activity? Neurochem Int. 2011;59:525–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pajęcka K, Wendel Nielsen C, Schousboe A, Waagepetersen HS, Plaitakis A. The effect of pH and ADP on ammonia affinity for human glutamate dehydrogenases. Metab Brain Dis. 2013;28:127–31.

    Article  PubMed  Google Scholar 

  28. Zhao L, Cao X, Li L, Wang X, Wang Q, Jiang S, Tang C, Zhou S, Xu N, Cui Y, Hu W, Fei L, Zheng Z, Chen L, Schmidt MO, Wei Q, Zhao J, Labes R, Patzak A, Wilcox CS, Fu X, Wellstein A, Yin La E. Acute kidney injury sensitizes the brain vasculature to Ang II (Angiotensin II) constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1). Hypertension. 2020;76:1924–34.

    Article  CAS  PubMed  Google Scholar 

  29. Pan HL. Brain angiotensin II and synaptic transmission. Neuroscientist. 2004;10:422–31.

    Article  CAS  PubMed  Google Scholar 

  30. Malek M. Brain consequences of acute kidney injury: focusing on the hippocampus. Kidney Res Clin Pract. 2018;37:315–22.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Arieff AI, Massry SG. Calcium metabolism of brain in acute renal failure. Effects of uremia, hemodialysis, and parathyroid hormone. J Clin Invest. 1974;53:387–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Leaf DE, Christov M. Dysregulated mineral metabolism in AKI. Semin Nephrol. 2019;39:41–56.

    Article  CAS  PubMed  Google Scholar 

  33. Akman C, Ülker Çakır D, Bakırdöğen S, Balcı S. The effect of serum calcium levels on uremic encephalopathy in patients with acute kidney injury in the emergency department. Medicina. 2019;55:1–5.

    Article  Google Scholar 

  34. Kielstein H, Suntharalingam M, Perthel R, Song R, Schneider SM, Martens-Lobenhoffer J, Jäger K, Bode-Böger SM, Kielstein JT. Role of the endogenous nitric oxide inhibitor asymmetric dimethylarginine (ADMA) and brain-derived neurotrophic factor (BDNF) in depression and behavioural changes: clinical and preclinical data in chronic kidney disease. Nephrol Dial Transplant. 2015;30:1699–705.

    Article  CAS  PubMed  Google Scholar 

  35. Solano-Flores LP, Rosas-Arellano MP, Ciriello J. Fos induction in central structures after afferent renal nerve stimulation. Brain Res. 1997;753:102–19.

    Article  CAS  PubMed  Google Scholar 

  36. Tanaka S, Okusa MD. Crosstalk between the nervous system and the kidney. Kidney Int. 2020;97:466–76.

    Article  PubMed  Google Scholar 

  37. Kopp UC, Cicha MZ, Smith LA. Endogenous angiotensin modulates PGE2-mediated release of substance P from renal mechanosensory nerve fibers. Am J Phys Regul Integr Comp Phys. 2002;282:19–30.

    Google Scholar 

  38. Bratton O, Martelli D, McKinley MJ, Trevaks D, Anderson CR, McAllen RM. Neural regulation of inflammation: no neural connection from the vagus to splenic sympathetic neurons. Exp Physiol. 2012;97:1180–5.

    Article  CAS  PubMed  Google Scholar 

  39. Martelli D, McKinley MJ, McAllen RM. The cholinergic anti-inflammatory pathway: a critical review. Auton Neurosci. 2014;182:65–9.

    Article  CAS  PubMed  Google Scholar 

  40. Gigliotti JC, Huang L, Bajwa A, Ye H, Mace EH, Hossack JA, Okusa MD. Ultrasound modulates the splenic neuroimmune axis in attenuating AKI. J Am Soc Nephrol. 2015;26:2470–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wasilczuk KM, Bayer KC, Somann JP, Albors GO, Sturgis J, Lyle LT, Irazoqui PP. Modulating the inflammatory reflex in rats using low-intensity focused ultrasound stimulation of the vagus nerve. Ultrasound Med Biol. 2019;45:481–9.

    Article  PubMed  Google Scholar 

  42. Peng B, Kong G, Yang C, Ming Y. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis. 2020;11(2):79. https://doi.org/10.1038/s41419-020-2276-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Suresh S, Rajvanshi PK, Noguchi CT. The many facets of erythropoietin physiologic and metabolic response. Front Physiol. 2020;10:1534. https://doi.org/10.3389/fphys.2019.01534.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Bi B, Guo J, Marlier A, Lin SR, Cantley LG. Erythropoietin expands a stromal cell population that can mediate renoprotection. Am J Physiol Renal Physiol. 2008;295(4):F1017–22. https://doi.org/10.1152/ajprenal.90218.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bernaudin M, Bellail A, Marti HH, Yvon A, Vivien D, Duchatelle I, Mackenzie ET, Petit E. Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. Glia. 2000;30:271–8.

    Article  CAS  PubMed  Google Scholar 

  46. Sirén AL, Knerlich F, Poser W, Gleiter CH, Brück W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001;101:271–6.

    Article  PubMed  Google Scholar 

  47. Silachev DN, Isaev NK, Pevzner IB, Zorova LD, Stelmashook EV, Novikova SV, Zorov DB. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk. PLoS One. 2012;7(12):e51553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Martinez-Estrada OM, Rodriguez-Millan E, Vicente EG, Reina M, Vilaro S, Fabre M. Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability. Eur J Neurosci. 2003;18:2538–44.

    Article  PubMed  Google Scholar 

  49. Onal EM, Sag AA, Sal O, Yerlikaya B, Afsar B, Kanbay M. Erythropoietin mediates brain-vascular-kidney crosstalk and may be a treatment target for pulmonary and resistant essential hypertension. Clin Exp Hypertens. 2017;39:197–209.

    Article  CAS  PubMed  Google Scholar 

  50. Shen J, Wu Y, Xu JY, Zhang J, Sinclair SH, Yanoff M, Xu GT. ERK- and Akt-dependent neuroprotection by erythropoietin (EPO) against glyoxal-AGEs via modulation of Bcl-xL, Bax, and BAD. Invest Opthalmol Vis Sci. 2010;51:35–46.

    Article  Google Scholar 

  51. Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, Robinson T, Heagerty PJ. A randomized trial of erythropoietin for neuroprotection in preterm infants. N Engl J Med. 2020;382:233–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, Bellomo R. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015;386:2499–506.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physiology Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Micaela Patti, Florencia Grynszpan & Victoria Ristagno-Ruiz

  2. Neurology Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Carlos Guillermo Videla

Authors
  1. Micaela Patti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florencia Grynszpan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria Ristagno-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Guillermo Videla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos Guillermo Videla .

Editor information

Editors and Affiliations

  1. Nephrology Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Carlos Guido Musso

  2. Grigore T. Popa University of Medicine, Iasi, Romania

    Adrian Covic

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Patti, M., Grynszpan, F., Ristagno-Ruiz, V., Videla, C.G. (2023). Kidney–Brain Crosstalk in Acute Kidney Injury. In: Musso, C.G., Covic, A. (eds) Organ Crosstalk in Acute Kidney Injury. Springer, Cham. https://doi.org/10.1007/978-3-031-36789-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-36789-2_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-36788-5

  • Online ISBN: 978-3-031-36789-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation