Skip to main content

Advertisement

Log in

Brain-derived neurotrophic factor (BDNF): a multifaceted marker in chronic kidney disease

  • Review article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Despite advances in diagnostic tools and therapeutic options, chronic kidney disease (CKD) is still a global health problem associated with increased morbidity and mortality. Insulin resistance, muscle wasting, malnutrition and chronic inflammation are highly prevalent in CKD patients. Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor-related family and with its receptor tropomyosin-related kinase receptor B impacts cell differentiation, synaptic connectivity and plasticity of the brain. BDNF is well studied in various populations especially in the area of neurology and psychiatry. Recently, there is also an acceleration of BDNF research in CKD and accumulating evidence suggests that BDNF may be a potential prognostic marker in CKD patients. Specifically, studies have shown that BDNF is associated with insulin resistance, muscle wasting, depression, oxidative stress and inflammation in CKD patients. However, the data regarding BDNF in CKD is only in its first steps and various issues must be highlighted in upcoming studies. In this review, we have summarized the findings regarding BDNF and its relationship between insulin resistance, muscle wasting, depression, oxidative stress and inflammation in CKD patients. We also mentioned controversies and possible causes for diverse findings and suggest perspectives in the context of BDNF and CKD.

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

References

  1. Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, Treviño-Becerra A, Wanner C. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73:391–8. https://doi.org/10.1038/sj.ki.5002585.

    Article  CAS  PubMed  Google Scholar 

  2. Wang XH, Mitch WE, Price SR. Pathophysiological mechanisms leading to muscle loss in chronic kidney disease. Nat Rev Nephrol. 2021. https://doi.org/10.1038/s41581-021-00498-0.

    Article  PubMed  Google Scholar 

  3. Deger SM, Hewlett JR, Gamboa J, Ellis CD, Hung AM, Siew ED, Mamnungu C, Sha F, Bian A, Stewart TG, Abumrad NN, Ikizler TA. Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease. Am J Physiol Endocrinol Metab. 2018;315:E1108-e1120. https://doi.org/10.1152/ajpendo.00070.2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pereira RA, Cordeiro AC, Avesani CM, Carrero JJ, Lindholm B, Amparo FC, Amodeo C, Cuppari L, Kamimura MA. Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality. Nephrol Dial Transpl. 2015;30:1718–25. https://doi.org/10.1093/ndt/gfv133.

    Article  CAS  Google Scholar 

  5. Ferreira MF, Böhlke M, Pauletto MB, Frühauf IR, Gonzalez MC. Sarcopenia diagnosis using different criteria as a predictor of early mortality in patients undergoing hemodialysis. Nutrition. 2022;95: 111542. https://doi.org/10.1016/j.nut.2021.111542.

    Article  PubMed  Google Scholar 

  6. Wilkinson TJ, Miksza J, Yates T, Lightfoot CJ, Baker LA, Watson EL, Zaccardi F, Smith AC. Association of sarcopenia with mortality and end-stage renal disease in those with chronic kidney disease: a UK Biobank study. J Cachexia Sarcopenia Muscle. 2021;12:586–98. https://doi.org/10.1002/jcsm.12705.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tian N, Chen N, Li PK. Depression in dialysis. Curr Opin Nephrol Hypertens. 2021;30:600–12. https://doi.org/10.1097/mnh.0000000000000741.

    Article  CAS  PubMed  Google Scholar 

  8. Hedayati SS, Minhajuddin AT, Afshar M, Toto RD, Trivedi MH, Rush AJ. Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death. JAMA. 2010;303:1946–53. https://doi.org/10.1001/jama.2010.619.

    Article  CAS  PubMed  Google Scholar 

  9. Poulianiti KP, Kaltsatou A, Mitrou GI, Jamurtas AZ, Koutedakis Y, Maridaki M, Stefanidis I, Sakkas GK, Karatzaferi C. Systemic redox imbalance in chronic kidney disease: a systematic review. Oxid Med Cell Longev. 2016;2016:8598253. https://doi.org/10.1155/2016/8598253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, Warady BA. Chronic inflammation in chronic kidney disease progression: role of Nrf2. Kidney Int Rep. 2021;6:1775–87. https://doi.org/10.1016/j.ekir.2021.04.023.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015;11:1164–78. https://doi.org/10.5114/aoms.2015.56342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989;341:149–52. https://doi.org/10.1038/341149a0.

    Article  CAS  PubMed  Google Scholar 

  13. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736. https://doi.org/10.1146/annurev.neuro.24.1.677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Adachi N, Numakawa T, Richards M, Nakajima S, Kunugi H. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: implications in brain-related diseases. World J Biol Chem. 2014;5:409–28. https://doi.org/10.4331/wjbc.v5.i4.409.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marshall J, Zhou XZ, Chen G, Yang SQ, Li Y, Wang Y, Zhang ZQ, Jiang Q, Birnbaumer L, Cao C. Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus. Proc Natl Acad Sci USA. 2018;115:E3549-e3558. https://doi.org/10.1073/pnas.1722493115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shen J, Maruyama IN. Brain-derived neurotrophic factor receptor TrkB exists as a preformed dimer in living cells. J Mol Signal. 2012;7:2. https://doi.org/10.1186/1750-2187-7-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zheng F, Zhou X, Moon C, Wang H. Regulation of brain-derived neurotrophic factor expression in neurons. Int J Physiol Pathophysiol Pharmacol. 2012;4:188–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bibel M, Barde YA. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000;14:2919–37. https://doi.org/10.1101/gad.841400.

    Article  CAS  PubMed  Google Scholar 

  19. Matusica D, Alfonsi F, Turner BJ, Butler TJ, Shepheard SR, Rogers ML, Skeldal S, Underwood CK, Mangelsdorf M, Coulson EJ. Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment. J Cell Sci. 2016;129:517–30. https://doi.org/10.1242/jcs.173864.

    Article  CAS  PubMed  Google Scholar 

  20. Cheng A, Wan R, Yang JL, Kamimura N, Son TG, Ouyang X, Luo Y, Okun E, Mattson MP. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nat Commun. 2012;3:1250. https://doi.org/10.1038/ncomms2238.

    Article  CAS  PubMed  Google Scholar 

  21. Matthews VB, Aström MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, Akerström T, Yfanti C, Broholm C, Mortensen OH, Penkowa M, Hojman P, Zankari A, Watt MJ, Bruunsgaard H, Pedersen BK, Febbraio MA. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009;52:1409–18. https://doi.org/10.1007/s00125-009-1364-1.

    Article  CAS  PubMed  Google Scholar 

  22. Delezie J, Handschin C. Endocrine crosstalk between skeletal muscle and the brain. Front Neurol. 2018;9:698. https://doi.org/10.3389/fneur.2018.00698.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rozanska O, Uruska A, Zozulinska-Ziolkiewicz D. Brain-derived neurotrophic factor and diabetes. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21030841.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chao MV, Rajagopal R, Lee FS. Neurotrophin signalling in health and disease. Clin Sci (Lond). 2006;110:167–73. https://doi.org/10.1042/cs20050163.

    Article  CAS  Google Scholar 

  25. Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer CP, Lindegaard B, Petersen AM, Taudorf S, Secher NH, Pilegaard H, Bruunsgaard H, Pedersen BK. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007;50:431–8. https://doi.org/10.1007/s00125-006-0537-4.

    Article  CAS  PubMed  Google Scholar 

  26. Karim A, Iqbal MS, Muhammad T, Qaisar R. Evaluation of sarcopenia using biomarkers of the neuromuscular junction in Parkinson’s disease. J Mol Neurosci. 2022. https://doi.org/10.1007/s12031-022-01970-7.

    Article  PubMed  Google Scholar 

  27. Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11:1169–80. https://doi.org/10.1017/s1461145708009309.

    Article  CAS  PubMed  Google Scholar 

  28. Laste G, Ripoll Rozisky J, de Macedo IC, Souza Dos Santos V, Custódio de Souza IC, Caumo W, Torres IL. Spinal cord brain-derived neurotrophic factor levels increase after dexamethasone treatment in male rats with chronic inflammation. NeuroImmunoModulation. 2013;20:119–25. https://doi.org/10.1159/000345995.

    Article  CAS  PubMed  Google Scholar 

  29. Huber LJ, Hempstead B, Donovan MJ. Neurotrophin and neurotrophin receptors in human fetal kidney. Dev Biol. 1996;179:369–81. https://doi.org/10.1006/dbio.1996.0268.

    Article  CAS  PubMed  Google Scholar 

  30. Giardino L, Armelloni S, Corbelli A, Mattinzoli D, Zennaro C, Guerrot D, Tourrel F, Ikehata M, Li M, Berra S, Carraro M, Messa P, Rastaldi MP. Podocyte glutamatergic signaling contributes to the function of the glomerular filtration barrier. J Am Soc Nephrol. 2009;20:1929–40. https://doi.org/10.1681/asn.2008121286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Armelloni S, Li M, Messa P, Rastaldi MP. Podocytes: a new player for glutamate signaling. Int J Biochem Cell Biol. 2012;44:2272–7. https://doi.org/10.1016/j.biocel.2012.09.014.

    Article  CAS  PubMed  Google Scholar 

  32. Vitureira N, Andrés R, Pérez-Martínez E, Martínez A, Bribián A, Blasi J, Chelliah S, López-Doménech G, De Castro F, Burgaya F, McNagny K, Soriano E. Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation. PLoS ONE. 2010;5: e12003. https://doi.org/10.1371/journal.pone.0012003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li M, Armelloni S, Ikehata M, Corbelli A, Pesaresi M, Calvaresi N, Giardino L, Mattinzoli D, Nisticò F, Andreoni S, Puliti A, Ravazzolo R, Forloni G, Messa P, Rastaldi MP. Nephrin expression in adult rodent central nervous system and its interaction with glutamate receptors. J Pathol. 2011;225:118–28. https://doi.org/10.1002/path.2923.

    Article  CAS  PubMed  Google Scholar 

  34. Cingolani LA, Goda Y. Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci. 2008;9:344–56. https://doi.org/10.1038/nrn2373.

    Article  CAS  PubMed  Google Scholar 

  35. Endlich N, Lange T, Kuhn J, Klemm P, Kotb AM, Siegerist F, Kindt F, Lindenmeyer MT, Cohen CD, Kuss AW, Nath N, Rettig R, Lendeckel U, Zimmermann U, Amann K, Stracke S, Endlich K. BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function. J Cell Mol Med. 2018;22:5265–77. https://doi.org/10.1111/jcmm.13762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Li M, Armelloni S, Zennaro C, Wei C, Corbelli A, Ikehata M, Berra S, Giardino L, Mattinzoli D, Watanabe S, Agostoni C, Edefonti A, Reiser J, Messa P, Rastaldi MP. BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization. J Pathol. 2015;235:731–44. https://doi.org/10.1002/path.4484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tao YS, Piao SG, Jin YS, Jin JZ, Zheng HL, Zhao HY, Lim SW, Yang CW, Li C. Expression of brain-derived neurotrophic factor in kidneys from normal and cyclosporine-treated rats. BMC Nephrol. 2018;19:63. https://doi.org/10.1186/s12882-018-0852-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cırrık S, Hacioglu G, Ayyıldız SN, Tezcan B, Abidin İ, Aydın-Abidin S, Noyan T. Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice. Adv Clin Expr Med. 2019;28:1161–70. https://doi.org/10.17219/acem/100647.

    Article  Google Scholar 

  39. Kurajoh M, Kadoya M, Morimoto A, Miyoshi A, Kanzaki A, Kakutani-Hatayama M, Hamamoto K, Shoji T, Moriwaki Y, Yamamoto T, Inaba M, Namba M, Koyama H. Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors—Hyogo Sleep Cardio-Autonomic Atherosclerosis study. PLoS ONE. 2017;12: e0178686. https://doi.org/10.1371/journal.pone.0178686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shin SJ, Yoon HE, Chung S, Kim YG, Kim DJ. Plasma brain-derived neurotrophic factor in hemodialysis patients. Int J Med Sci. 2012;9:772–7. https://doi.org/10.7150/ijms.5063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zoladz JA, Śmigielski M, Majerczak J, Nowak ŁR, Zapart-Bukowska J, Smoleński O, Kulpa J, Duda K, Drzewińska J, Bartosz G. Hemodialysis decreases serum brain-derived neurotrophic factor concentration in humans. Neurochem Res. 2012;37:2715–24. https://doi.org/10.1007/s11064-012-0862-6.

    Article  CAS  PubMed  Google Scholar 

  42. Zhu B, Jin LN, Shen JQ, Liu JF, Jiang RY, Yang L, Zhang J, Luo AL, Miao LY, Yang C. Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: a prospective single-center cohort study. Sci Rep. 2018;8:12250. https://doi.org/10.1038/s41598-018-29760-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hung AM, Ikizler TA. Factors determining insulin resistance in chronic hemodialysis patients. Contrib Nephrol. 2011;171:127–34. https://doi.org/10.1159/000327177.

    Article  CAS  PubMed  Google Scholar 

  44. Spoto B, Pisano A, Zoccali C. Insulin resistance in chronic kidney disease: a systematic review. Am J Physiol Ren Physiol. 2016;311:F1087-f1108. https://doi.org/10.1152/ajprenal.00340.2016.

    Article  CAS  Google Scholar 

  45. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol. 2001;15:1748–57. https://doi.org/10.1210/mend.15.10.0706.

    Article  CAS  PubMed  Google Scholar 

  46. Nonomura T, Tsuchida A, Ono-Kishino M, Nakagawa T, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates energy expenditure through the central nervous system in obese diabetic mice. Int J Expr Diabetes Res. 2001;2:201–9. https://doi.org/10.1155/edr.2001.201.

    Article  CAS  Google Scholar 

  47. Jin H, Zhu Y, Li Y, Ding X, Ma W, Han X, Wang B. BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury. Apoptosis. 2019;24:511–28. https://doi.org/10.1007/s10495-019-01535-x.

    Article  CAS  PubMed  Google Scholar 

  48. Tsuchida A, Nonomura T, Ono-Kishino M, Nakagawa T, Taiji M, Noguchi H. Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice. Int J Obes Relat Metab Disord. 2001;25:1286–93. https://doi.org/10.1038/sj.ijo.0801678.

    Article  CAS  PubMed  Google Scholar 

  49. Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000;49:436–44. https://doi.org/10.2337/diabetes.49.3.436.

    Article  CAS  PubMed  Google Scholar 

  50. Tsuchida A, Nakagawa T, Itakura Y, Ichihara J, Ogawa W, Kasuga M, Taiji M, Noguchi H. The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice. Diabetologia. 2001;44:555–66. https://doi.org/10.1007/s001250051661.

    Article  CAS  PubMed  Google Scholar 

  51. Kuroda A, Yamasaki Y, Matsuhisa M, Kubota M, Nakahara I, Nakatani Y, Hoshi A, Gorogawa S, Umayahara Y, Itakura Y, Nakagawa T, Taiji M, Kajimoto Y, Hori M. Brain-derived neurotrophic factor ameliorates hepatic insulin resistance in Zucker fatty rats. Metabolism. 2003;52:203–8. https://doi.org/10.1053/meta.2003.50026.

    Article  CAS  PubMed  Google Scholar 

  52. Shamsi-Goushki A, Mortazavi Z, Mirshekar MA, Behrasi F, Moradi-Kor N, Taghvaeefar R. Effects of high white and brown sugar consumption on serum level of brain-derived neurotrophic factor, insulin resistance, and body weight in albino rats. J Obes Metab Syndr. 2020;29:320–4. https://doi.org/10.7570/jomes20037.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Uruska A, Niedzwiecki P, Araszkiewicz A, Zozulinska-Ziolkiewicz D. Brain-derived neurotrophic factor and insulin resistance during hyperinsulinaemic-euglycaemic clamp in type 1 diabetes patients in the PoProStu. Diabetes Metab. 2017;43:472–4. https://doi.org/10.1016/j.diabet.2016.12.007.

    Article  CAS  PubMed  Google Scholar 

  54. Boyuk B, Degirmencioglu S, Atalay H, Guzel S, Acar A, Celebi A, Ekizoglu I, Simsek C. Relationship between levels of brain-derived neurotrophic factor and metabolic parameters in patients with type 2 diabetes mellitus. J Diabetes Res. 2014;2014: 978143. https://doi.org/10.1155/2014/978143.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Fujinami A, Ohta K, Obayashi H, Fukui M, Hasegawa G, Nakamura N, Kozai H, Imai S, Ohta M. Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem. 2008;41:812–7. https://doi.org/10.1016/j.clinbiochem.2008.03.003.

    Article  CAS  PubMed  Google Scholar 

  56. Suwa M, Kishimoto H, Nofuji Y, Nakano H, Sasaki H, Radak Z, Kumagai S. Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabolism. 2006;55:852–7. https://doi.org/10.1016/j.metabol.2006.02.012.

    Article  CAS  PubMed  Google Scholar 

  57. Toloza FJK, Pérez-Matos MC, Ricardo-Silgado ML, Morales-Álvarez MC, Mantilla-Rivas JO, Pinzón-Cortés JA, Pérez-Mayorga M, Arévalo-García ML, Tolosa-González G, Mendivil CO. Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance. J Diabetes Complicat. 2017;31:1423–9. https://doi.org/10.1016/j.jdiacomp.2017.06.002.

    Article  CAS  Google Scholar 

  58. Marchelek-Myśliwiec M, Cichocka E, Dziedziejko V, Dutkiewicz G, Stępniewska J, Safranow K, Budkowska M, Sałata D, Syrenicz A, Machaliński B, Ciechanowski K. Insulin resistance and brain-derived neurotrophic factor levels in chronic kidney disease. Ann Clin Biochem. 2015;52:213–9. https://doi.org/10.1177/0004563214533514.

    Article  CAS  PubMed  Google Scholar 

  59. Navaratna D, Guo SZ, Hayakawa K, Wang X, Gerhardinger C, Lo EH. Decreased cerebrovascular brain-derived neurotrophic factor-mediated neuroprotection in the diabetic brain. Diabetes. 2011;60:1789–96. https://doi.org/10.2337/db10-1371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nazeem M, Wahdan SA, El-Naga RN, Gad AM. Saxagliptin ameliorated the depressive-like behavior induced by chronic unpredictable mild stress in rats: Impact on incretins and AKT/PI3K pathway. Eur J Pharmacol. 2021;912: 174602. https://doi.org/10.1016/j.ejphar.2021.174602.

    Article  CAS  PubMed  Google Scholar 

  61. Baghcheghi Y, Beheshti F, Salmani H, Hosseini M. Brain-derived neurotrophic factor and nitric oxide contribute to protective effects of rosiglitazone on learning and memory in hypothyroid rats. Acta Neurobiol Exp (Wars). 2021;81:218–32. https://doi.org/10.21307/ane-2021-021.

    Article  Google Scholar 

  62. Sritawan N, Suwannakot K, Naewla S, Chaisawang P, Aranarochana A, Sirichoat A, Pannangrong W, Wigmore P, Welbat JU. Effect of metformin treatment on memory and hippocampal neurogenesis decline correlated with oxidative stress induced by methotrexate in rats. Biomed Pharmacother. 2021;144: 112280. https://doi.org/10.1016/j.biopha.2021.112280.

    Article  CAS  PubMed  Google Scholar 

  63. Sedky AA. Improvement of cognitive function, glucose and lipid homeostasis and serum osteocalcin levels by liraglutide in diabetic rats. Fundam Clin Pharmacol. 2021;35:989–1003. https://doi.org/10.1111/fcp.12664.

    Article  CAS  PubMed  Google Scholar 

  64. Wiciński M, Wódkiewicz E, Górski K, Walczak M, Malinowski B. Perspective of SGLT2 Inhibition in treatment of conditions connected to neuronal loss: focus on Alzheimer’s disease and ischemia-related brain injury. Pharmaceuticals (Basel). 2020. https://doi.org/10.3390/ph13110379.

    Article  Google Scholar 

  65. Gadelha AB, Cesari M, Corrêa HL, Neves RVP, Sousa CV, Deus LA, Souza MK, Reis AL, Moraes MR, Prestes J, Simões HG, Andrade RV, Melo GF, Rosa TS. Effects of pre-dialysis resistance training on sarcopenia, inflammatory profile, and anemia biomarkers in older community-dwelling patients with chronic kidney disease: a randomized controlled trial. Int Urol Nephrol. 2021;53:2137–47. https://doi.org/10.1007/s11255-021-02799-6.

    Article  CAS  PubMed  Google Scholar 

  66. Deleaval P, Luaire B, Laffay P, Jambut-Cadon D, Stauss-Grabo M, Canaud B, Chazot C. Short-term effects of branched-chain amino acids-enriched dialysis fluid on branched-chain amino acids plasma level and mass balance: a randomized cross-over study. J Ren Nutr. 2020;30:61–8. https://doi.org/10.1053/j.jrn.2019.03.079.

    Article  CAS  PubMed  Google Scholar 

  67. Mitch WE, Price SR. Mechanisms activated by kidney disease and the loss of muscle mass. Am J Kidney Dis. 2001;38:1337–42. https://doi.org/10.1053/ajkd.2001.29249.

    Article  CAS  PubMed  Google Scholar 

  68. Martins AM, Dias Rodrigues JC, de Oliveira Santin FG, Barbosa Brito Fdos S, Bello Moreira AS, Lourenço RA, Avesani CM. Food intake assessment of elderly patients on hemodialysis. J Ren Nutr. 2015;25:321–6. https://doi.org/10.1053/j.jrn.2014.10.007.

    Article  PubMed  Google Scholar 

  69. Afsar B, Siriopol D, Aslan G, Eren OC, Dagel T, Kilic U, Kanbay A, Burlacu A, Covic A, Kanbay M. The impact of exercise on physical function, cardiovascular outcomes and quality of life in chronic kidney disease patients: a systematic review. Int Urol Nephrol. 2018;50:885–904. https://doi.org/10.1007/s11255-018-1790-4.

    Article  PubMed  Google Scholar 

  70. Bakaloudi DR, Siargkas A, Poulia KA, Dounousi E, Chourdakis M. The effect of exercise on nutritional status and body composition in hemodialysis: a systematic review. Nutrients. 2020. https://doi.org/10.3390/nu12103071.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25:295–301. https://doi.org/10.1016/s0166-2236(02)02143-4.

    Article  CAS  PubMed  Google Scholar 

  72. Yu T, Chang Y, Gao XL, Li H, Zhao P. Dynamic expression and the role of BDNF in exercise-induced skeletal muscle regeneration. Int J Sports Med. 2017;38:959–66. https://doi.org/10.1055/s-0043-118343.

    Article  CAS  PubMed  Google Scholar 

  73. Tonoli C, Heyman E, Buyse L, Roelands B, Piacentini MF, Bailey S, Pattyn N, Berthoin S, Meeusen R. Neurotrophins and cognitive functions in T1D compared with healthy controls: effects of a high-intensity exercise. Appl Physiol Nutr Metab. 2015;40:20–7. https://doi.org/10.1139/apnm-2014-0098.

    Article  CAS  PubMed  Google Scholar 

  74. Guilherme J, Semenova EA, Borisov OV, Kostryukova ES, Vepkhvadze TF, Lysenko EA, Andryushchenko ON, Andryushchenko LB, Lednev EM, Larin AK, Bondareva EA, Generozov EV, Ahmetov II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res. 2020. https://doi.org/10.1519/jsc.0000000000003756.

    Article  PubMed  Google Scholar 

  75. Pinho RA, Aguiar AS Jr, Radák Z. Effects of resistance exercise on cerebral redox regulation and cognition: an interplay between muscle and brain. Antioxidants (Basel). 2019. https://doi.org/10.3390/antiox8110529.

    Article  Google Scholar 

  76. Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. J Clin Invest. 2019;129:2542–54. https://doi.org/10.1172/jci126859.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kim M, Sujkowski A, Namkoong S, Gu B, Cobb T, Kim B, Kowalsky AH, Cho CS, Semple I, Ro SH, Davis C, Brooks SV, Karin M, Wessells RJ, Lee JH. Sestrins are evolutionarily conserved mediators of exercise benefits. Nat Commun. 2020;11:190. https://doi.org/10.1038/s41467-019-13442-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Corrêa HL, Neves RVP, Deus LA, Reis AL, Simões HG, Navalta JW, Prestes J, Moraes MR, Rosa TS. Could sestrins 2 be the secret of resistance exercise benefiting dialytic patients? Nephrol Dial Transplant. 2020;35:2198–9. https://doi.org/10.1093/ndt/gfaa212.

    Article  PubMed  Google Scholar 

  79. Matsumoto J, Takada S, Kinugawa S, Furihata T, Nambu H, Kakutani N, Tsuda M, Fukushima A, Yokota T, Tanaka S, Takahashi H, Watanabe M, Hatakeyama S, Matsumoto M, Nakayama KI, Otsuka Y, Sabe H, Tsutsui H, Anzai T. Brain-derived neurotrophic factor improves limited exercise capacity in mice with heart failure. Circulation. 2018;138:2064–6. https://doi.org/10.1161/circulationaha.118.035212.

    Article  PubMed  Google Scholar 

  80. Matsumoto J, Takada S, Furihata T, Nambu H, Kakutani N, Maekawa S, Mizushima W, Nakano I, Fukushima A, Yokota T, Tanaka S, Handa H, Sabe H, Kinugawa S. Brain-derived neurotrophic factor improves impaired fatty acid oxidation via the activation of adenosine monophosphate-activated protein kinase-ɑ - proliferator-activated receptor-r coactivator-1ɑ signaling in skeletal muscle of mice with heart failure. Circ Heart Fail. 2021;14: e005890. https://doi.org/10.1161/circheartfailure.119.005890.

    Article  CAS  PubMed  Google Scholar 

  81. Damirchi A, Tehrani BS, Alamdari KA, Babaei P. Influence of aerobic training and detraining on serum BDNF, insulin resistance, and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome. Clin J Sport Med. 2014;24:513–8. https://doi.org/10.1097/jsm.0000000000000082.

    Article  PubMed  Google Scholar 

  82. Dinoff A, Herrmann N, Swardfager W, Liu CS, Sherman C, Chan S, Lanctôt KL. The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PLoS ONE. 2016;11: e0163037. https://doi.org/10.1371/journal.pone.0163037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rojas Vega S, Strüder HK, Vera Wahrmann B, Schmidt A, Bloch W, Hollmann W. Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res. 2006;1121:59–65. https://doi.org/10.1016/j.brainres.2006.08.105.

    Article  CAS  PubMed  Google Scholar 

  84. Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol. 2003;138:99–105. https://doi.org/10.1016/s0165-5728(03)00121-8.

    Article  CAS  PubMed  Google Scholar 

  85. Nuvagah Forti L, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, Bautmans I. High versus low load resistance training: the effect of 24 weeks detraining on serum brain-derived-neurotrophic factor (BDNF) in older adults. J Frailty Aging. 2017;6:53–8. https://doi.org/10.14283/jfa.2017.2.

    Article  CAS  PubMed  Google Scholar 

  86. Deus LA, Corrêa HL, Neves RVP, Reis AL, Honorato FS, Silva VL, Souza MK, de Araújo TB, de Gusmão Alves LS, Sousa CV, Reis TL, de Aguiar LS, Simões HG, Prestes J, Melo GF, Rosa TS. Are resistance training-induced bdnf in hemodialysis patients associated with depressive symptoms, quality of life, antioxidant capacity, and muscle strength? an insight for the muscle-brain-renal axis. Int J Environ Res Public Health. 2021. https://doi.org/10.3390/ijerph182111299.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Miyazaki S, Iino N, Koda R, Narita I, Kaneko Y. Brain-derived neurotrophic factor is associated with sarcopenia and frailty in Japanese hemodialysis patients. Geriatr Gerontol Int. 2021;21:27–33. https://doi.org/10.1111/ggi.14089.

    Article  PubMed  Google Scholar 

  88. Koito Y, Yanishi M, Kimura Y, Tsukaguchi H, Kinoshita H, Matsuda T. Serum brain-derived neurotrophic factor and myostatin levels are associated with skeletal muscle mass in kidney transplant recipients. Transplant Proc. 2021;53:1939–44. https://doi.org/10.1016/j.transproceed.2021.04.021.

    Article  CAS  PubMed  Google Scholar 

  89. Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, Pellegrini F, Saglimbene V, Logroscino G, Fishbane S, Strippoli GF. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int. 2013;84:179–91. https://doi.org/10.1038/ki.2013.77.

    Article  PubMed  Google Scholar 

  90. Campbell KH, Huang ES, Dale W, Parker MM, John PM, Young BA, Moffet HH, Laiteerapong N, Karter AJ. Association between estimated GFR, health-related quality of life, and depression among older adults with diabetes: the diabetes and aging study. Am J Kidney Dis. 2013;62:541–8. https://doi.org/10.1053/j.ajkd.2013.03.039.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Duncan LE, Hutchison KE, Carey G, Craighead WE. Variation in brain-derived neurotrophic factor (BDNF) gene is associated with symptoms of depression. J Affect Disord. 2009;115:215–9. https://doi.org/10.1016/j.jad.2008.08.016.

    Article  CAS  PubMed  Google Scholar 

  92. Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;64:527–32. https://doi.org/10.1016/j.biopsych.2008.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zhou C, Zhong J, Zou B, Fang L, Chen J, Deng X, Zhang L, Zhao X, Qu Z, Lei Y, Lei T. Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression. PLoS ONE. 2017;12: e0172270. https://doi.org/10.1371/journal.pone.0172270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lee HY, Kim YK. Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants. Neuropsychobiology. 2008;57:194–9. https://doi.org/10.1159/000149817.

    Article  CAS  PubMed  Google Scholar 

  95. Sun CY, Li JR, Wang YY, Lin SY, Ou YC, Lin CJ, Wang JD, Liao SL, Chen CJ. Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy. Aging (Albany NY). 2021;13:6681–701. https://doi.org/10.18632/aging.202523.

    Article  CAS  Google Scholar 

  96. Sun CY, Li JR, Wang YY, Lin SY, Ou YC, Lin CJ, Wang JD, Liao SL, Chen CJ. p-Cresol sulfate caused behavior disorders and neurodegeneration in mice with unilateral nephrectomy involving oxidative stress and neuroinflammation. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21186687.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Haghighat N, Rajabi S, Mohammadshahi M. Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in hemodialysis patients: a randomized, double-blinded, clinical trial. Nutr Neurosci. 2021;24:490–9. https://doi.org/10.1080/1028415x.2019.1646975.

    Article  CAS  PubMed  Google Scholar 

  98. 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. https://doi.org/10.1093/ndt/gfv253.

    Article  CAS  PubMed  Google Scholar 

  99. Eraldemir FC, Ozsoy D, Bek S, Kir H, Dervisoglu E. The relationship between brain-derived neurotrophic factor levels, oxidative and nitrosative stress and depressive symptoms: a study on peritoneal dialysis. Ren Fail. 2015;37:722–6. https://doi.org/10.3109/0886022x.2015.1011551.

    Article  CAS  PubMed  Google Scholar 

  100. Alshogran OY, Khalil AA, Oweis AO, Altawalbeh SM, Alqudah MAY. Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients. Gen Hosp Psychiatry. 2018;53:25–31. https://doi.org/10.1016/j.genhosppsych.2018.04.003.

    Article  PubMed  Google Scholar 

  101. Wang LJ, Chen CK, Hsu HJ, Wu IW, Sun CY, Lee CC. Depression, 5HTTLPR and BDNF Val66Met polymorphisms, and plasma BDNF levels in hemodialysis patients with chronic renal failure. Neuropsychiatr Dis Treat. 2014;10:1235–41. https://doi.org/10.2147/ndt.S54277.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Ebert T, Neytchev O, Witasp A, Kublickiene K, Stenvinkel P, Shiels PG. Inflammation and oxidative stress in chronic kidney disease and dialysis patients. Antioxid Redox Signal. 2021;35:1426–48. https://doi.org/10.1089/ars.2020.8184.

    Article  CAS  PubMed  Google Scholar 

  103. Malgorzewicz S, Lichodziejewska-Niemierko M, Rutkowski B, Lysiak-Szydlowska W. Nutritional status and oxidative processes in diabetic and nondiabetic peritoneal dialysis patients. J Ren Nutr. 2004;14:242–7.

    Article  PubMed  Google Scholar 

  104. Chen SD, Wu CL, Hwang WC, Yang DI. More insight into BDNF against neurodegeneration: anti-apoptosis, anti-oxidation, and suppression of autophagy. Int J Mol Sci. 2017. https://doi.org/10.3390/ijms18030545.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Hacioglu G, Senturk A, Ince I, Alver A. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model. Iran J Basic Med Sci. 2016;19:388–93.

    PubMed  PubMed Central  Google Scholar 

  106. He T, Katusic ZS. Brain-derived neurotrophic factor increases expression of MnSOD in human circulating angiogenic cells. Microvasc Res. 2012;83:366–71. https://doi.org/10.1016/j.mvr.2012.01.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Siamilis S, Jakus J, Nyakas C, Costa A, Mihalik B, Falus A, Radak Z. The effect of exercise and oxidant-antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats. Spinal Cord. 2009;47:453–7. https://doi.org/10.1038/sc.2008.125.

    Article  CAS  PubMed  Google Scholar 

  108. Kapczinski F, Frey BN, Andreazza AC, Kauer-Sant’Anna M, Cunha AB, Post RM. Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes. Braz J Psychiatr. 2008;30:243–5. https://doi.org/10.1590/s1516-44462008000300011.

    Article  Google Scholar 

  109. Ali MR, Abo-Youssef AM, Messiha BA, Khattab MM. Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:637–56. https://doi.org/10.1007/s00210-016-1234-6.

    Article  CAS  PubMed  Google Scholar 

  110. Ogura Y, Sato K, Kawashima K, Kobayashi N, Imura S, Fujino K, Kawaguchi H, Nedachi T. Subtoxic levels of hydrogen peroxide induce brain-derived neurotrophic factor expression to protect PC12 cells. BMC Res Notes. 2014;7:840. https://doi.org/10.1186/1756-0500-7-840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Stenvinkel P, Alvestrand A. Inflammation in end-stage renal disease: sources, consequences, and therapy. Semin Dial. 2002;15:329–37. https://doi.org/10.1046/j.1525-139x.2002.00083.x.

    Article  PubMed  Google Scholar 

  112. Hanna RM, Ghobry L, Wassef O, Rhee CM, Kalantar-Zadeh K. A practical approach to nutrition, protein-energy wasting, sarcopenia, and cachexia in patients with chronic kidney disease. Blood Purif. 2020;49:202–11. https://doi.org/10.1159/000504240.

    Article  CAS  PubMed  Google Scholar 

  113. Anand S, Chertow GM, Johansen KL, Grimes B, Kurella Tamura M, Dalrymple LS, Kaysen GA. Association of self-reported physical activity with laboratory markers of nutrition and inflammation: the comprehensive dialysis study. J Ren Nutr. 2011;21:429–37. https://doi.org/10.1053/j.jrn.2010.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Nowak Ł, Adamczak M, Więcek A. Is inflammation a new risk factor of depression in haemodialysis patients? Int Urol Nephrol. 2013;45:1121–8. https://doi.org/10.1007/s11255-012-0269-y.

    Article  CAS  PubMed  Google Scholar 

  115. Yang L, Gong NR, Zhang Q, Ma YB, Zhou H. Apparent correlations between AMPK expression and brain inflammatory response and neurological function factors in rats with chronic renal failure. J Mol Neurosci. 2019;68:204–13. https://doi.org/10.1007/s12031-019-01299-8.

    Article  CAS  PubMed  Google Scholar 

  116. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost. 2002;87:728–34.

    Article  CAS  PubMed  Google Scholar 

  117. Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L, Miller JA, Welcher AA. Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif. 1995;6:465–71. https://doi.org/10.1006/prep.1995.1062.

    Article  CAS  PubMed  Google Scholar 

  118. Lee BC, Choi IG, Kim YK, Ham BJ, Yang BH, Roh S, Choi J, Lee JS, Oh DY, Chai YG. Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence. Alcohol. 2009;43:265–9. https://doi.org/10.1016/j.alcohol.2009.04.003.

    Article  CAS  PubMed  Google Scholar 

  119. Nofuji Y, Suwa M, Sasaki H, Ichimiya A, Nishichi R, Kumagai S. Different circulating brain-derived neurotrophic factor responses to acute exercise between physically active and sedentary subjects. J Sports Sci Med. 2012;11:83–8.

    PubMed  PubMed Central  Google Scholar 

  120. Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A, Bianchi C, Mannari C, Martini C, Da Pozzo E, Schiavi E, Mariotti A, Roncaglia I, Palla A, Consoli G, Giovannini L, Massimetti G, Dell’Osso L. Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord. 2008;105:279–83. https://doi.org/10.1016/j.jad.2007.05.005.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Baris Afsar.

Ethics declarations

Conflicts of interest

None declared.

Additional information

Publisher's Note

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

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afsar, B., Afsar, R.E. Brain-derived neurotrophic factor (BDNF): a multifaceted marker in chronic kidney disease. Clin Exp Nephrol 26, 1149–1159 (2022). https://doi.org/10.1007/s10157-022-02268-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-022-02268-z

Keywords

Navigation