Advertisement

Metabolic Brain Disease

, Volume 33, Issue 5, pp 1641–1648 | Cite as

Association between abnormal thalamic metabolites and sleep disturbance in patients with end-stage renal disease

  • Xueying Ma
  • Yan Zhang
  • Shaohui Ma
  • Peng Li
  • Dun Ding
  • Hua Liu
  • Jixin Liu
  • Ming Zhang
Original Article
  • 71 Downloads

Abstract

Sleep disturbances are common in end-stage renal disease (ESRD) patients. However, the underlying neuropathological mechanisms are largely unclear. Previous studies have revealed the important role of the thalamus in the potential mechanisms of sleep disorders. We hypothesized that the sleep disturbances in ESRD patients may correspond to metabolic changes of thalamus and the uremic factors may have a vital contribution on these changes. We performed multi-voxel 1H-MRS of bilateral thalami in 27 ESRD patients who currently receiving hemodialysis treatment and 21 age-matched healthy volunteers. ESRD patients underwent Pittsburgh Sleep Quality Index (PSQI) scale and restless legs syndrome (RLS) rating scale assessment. Laboratory blood tests including serum creatinine, serum urea, cystatin-C, serum parathyroid hormone (PTH), calcium and phosphorus levels, hemoglobin and hematocrit were performed in all ESRD patients close to the time of the MR examination. We found correlations among elevated PTH, higher PSQI score and RLS rating score in ESRD patients. ESRD patients displayed decreased N-acetylaspartate and creatine ratio (NAA/Cr) of thalami compared with controls. There were significantly negative correlation between NAA/Cr and serum PTH level or PSQI score. The metabolic changes of thalami played an important role in the neuropathological mechanisms of lower sleep quality in ESRD patients. Secondary hyperparathyroidism as one of the main uremia-related factors was closely related to abnormal metabolites of the thalamus in patients with ESRD, revealing the crosstalk procedure between renal impairment and brain function.

Keywords

End-stage renal disease Magnetic resonance spectroscopy Sleep quality Metabolites Thalamus 

Notes

Acknowledgements

Ming Zhang and Ji-xin Liu were responsible for the design and study concept. Xue-ying Ma, Yan Zhang, Shao-hui Ma contributed to the data acquisition. Xue-ying Ma, Yan Zhang, Shaohui Ma, Peng Li and Dun Ding contributed to the data analysis and interpretation of findings. Xue-ying Ma drafted the manuscript. Ji-xin Liu and Ming Zhang revised the manuscript. Xue-ying Ma and Yan Zhang contributed equally to this work. All authors critically reviewed the manuscript and approved the final version for publication. This research was supported by the National Natural Science Foundation of China (Grant No. 81371530, 81571640 and 81471737) and Natural Science Foundation of Shaanxi Province of China (Grant No. 2017ZDJC-13).

Funding

This research was supported by the National Natural Science Foundation of China (Grant No. 81371530 and 81571640) and Natural Science Foundation of Shaanxi Province of China (Grant No. 2017ZDJC-13).

Compliance with ethical standards

Conflict of interest

The authors disclose no conflicts.

References

  1. Allen RP, Barker PB, Horska A, Earley CJ (2013) Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology 80:2028–2034.  https://doi.org/10.1212/WNL.0b013e318294b3f6 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB (2014) Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated international restless legs syndrome study group (IRLSSG) consensus criteria – history, rationale, description, and significance. Sleep Med 15:860–873.  https://doi.org/10.1016/j.sleep.2014.03.025 CrossRefPubMedGoogle Scholar
  3. Benz RL, Pressman MR, Hovick ET, Peterson DD (2000) Potential novel predictors of mortality in end-stage renal disease patients with sleep disorders. Am J Kidney Dis 35:1052–1060.  https://doi.org/10.1016/S0272-6386(00)70039-4 CrossRefPubMedGoogle Scholar
  4. Brenner R, Munro P, Williams SC, Bell JD, Barker G, Hawkins C, Landon D, McDonald W (1993) The proton NMR spectrum in acute EAE: the significance of the change in the Cho: Cr ratio. Magn Reson Med 29:737–745CrossRefPubMedGoogle Scholar
  5. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92:1087–1187.  https://doi.org/10.1152/physrev.00032.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bugnicourt JM, Godefroy O, Chillon JM, Choukroun G, Massy ZA (2013) Cognitive disorders and dementia in CKD: the neglected kidney-brain axis. J Am Soc Nephrol 24:353–363.  https://doi.org/10.1681/asn.2012050536 CrossRefPubMedGoogle Scholar
  7. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res 28:193–213CrossRefPubMedGoogle Scholar
  8. Castillo M, Kwock L, Mukherji SK (1996) Clinical applications of proton MR spectroscopy. Am J Neuroradiol 17:1–16PubMedGoogle Scholar
  9. Chai C, Yan S, Chu Z, Wang T, Wang L, Zhang M, Zuo C, Haacke EM, Xia S, Shen W (2015) Quantitative measurement of brain iron deposition in patients with haemodialysis using susceptibility mapping. Metab Brain Dis 30:563–571.  https://doi.org/10.1007/s11011-014-9608-2 CrossRefPubMedGoogle Scholar
  10. Chou F-F, Chen J-B, Hsieh K-C, Liou C-W (2008) Cognitive changes after parathyroidectomy in patients with secondary hyperparathyroidism. Surgery 143:526–532.  https://doi.org/10.1016/j.surg.2007.11.019 CrossRefPubMedGoogle Scholar
  11. Cortelli P, Perani D, Parchi P, Grassi F, Montagna P, De Martin M, Castellani R, Tinuper P, Gambetti P, Lugaresi E, Fazio F (1997) Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein. Neurology 49:126–133CrossRefPubMedGoogle Scholar
  12. Coulon P, Budde T, Pape HC (2012) The sleep relay--the role of the thalamus in central and decentral sleep regulation. Pflugers Arch 463:53–71.  https://doi.org/10.1007/s00424-011-1014-6 CrossRefPubMedGoogle Scholar
  13. Drüeke TB, Eckardt KU (2002) Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients. Nephrol Dial Transplant 17:28–31.  https://doi.org/10.1093/ndt/17.suppl_5.28 CrossRefPubMedGoogle Scholar
  14. Esposito MG, Cesare CM, De Santo RM, Cice G, Perna AF, Violetti E, Conzo G, Bilancio G, Celsi S, Annunziata F, Iannelli S, De Santo NG, Cirillo M, Livrea A (2008) Parathyroidectomy improves the quality of sleep in maintenance hemodialysis patients with severe hyperparathyroidism. J Nephrol 21 Suppl 13:S92–S96Google Scholar
  15. Fazekas G, Fazekas F, Schmidt R, Flooh E, Valetitsch H, Kapeller P, Krejs GJ (1996) Pattern of cerebral blood flow and cognition in patients undergoing chronic haemodialysis treatment. Nucl Med Commun 17:603–608CrossRefPubMedGoogle Scholar
  16. Ferrarelli F, Peterson MJ, Sarasso S, Riedner BA, Murphy MJ, Benca RM, Bria P, Kalin NH, Tononi G (2010) Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles. Am J Psychiatry 167:1339–1348.  https://doi.org/10.1176/appi.ajp.2010.09121731 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Foley RN, Collins AJ (2007) End-stage renal disease in the United States: an update from the United States renal data system. J Am Soc Nephrol 18:2644–2648.  https://doi.org/10.1681/asn.2007020220 CrossRefPubMedGoogle Scholar
  18. Geissler A, Fründ R, Kohler S, Eichhorn HM, Krämer B, Feuerbach S (1995) Cerebral metabolite patterns in dialysis patients: evaluation with H-1 MR spectroscopy. Radiology 194:693–697CrossRefPubMedGoogle Scholar
  19. Hanly PJ, Gabor JY, Chan C, Pierratos A (2003) Daytime sleepiness in patients with CRF: impact of nocturnal hemodialysis. Am J Kidney Dis 41:403–410.  https://doi.org/10.1053/ajkd.2003.50066 CrossRefPubMedGoogle Scholar
  20. Hollander M, Bots M, Del Sol AI, Koudstaal PJ, Witteman J, Grobbee D, Hofman A, Breteler M (2002) Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly. Circulation 105:2872–2877CrossRefPubMedGoogle Scholar
  21. Jorde R, Waterloo K, Saleh F, Haug E, Svartberg J (2006) Neuropsychological function in relation to serum parathyroid hormone and serum 25–hydroxyvitamin D levels. J Neurol 253:464–470CrossRefPubMedGoogle Scholar
  22. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. (2002) Am J Kidney Dis 39:S1–266Google Scholar
  23. Khudaverdyan D, Asratyan A (1996) Effect of the parathyroid hormone—calcium system on functional activity of the hypothalamus-neurohypophysis complex. Bull Exp Biol Med 122:1069–1071CrossRefGoogle Scholar
  24. Kuwabara Y, Sasaki M, Hirakata H, Koga H, Nakagawa M, Chen T, Kaneko K, Masuda K, Fujishima M (2002) Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failure. Kidney Int 61:564–569.  https://doi.org/10.1046/j.1523-1755.2002.00142.x CrossRefPubMedGoogle Scholar
  25. Lu R, Kiernan MC, Murray A, Rosner MH, Ronco C (2015) Kidney-brain crosstalk in the acute and chronic setting. Nat Rev Nephrol 11:707–719.  https://doi.org/10.1038/nrneph.2015.131 CrossRefPubMedGoogle Scholar
  26. Ma X, Tian J, Wu Z, Zong X, Dong J, Zhan W, Xu Y, Li Z, Jiang G (2016) Spatial disassociation of disrupted functional connectivity for the default mode network in patients with end-stage renal disease. PLoS One 11:e0161392.  https://doi.org/10.1371/journal.pone.0161392 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Malberti F, Marcelli D, Conte F, Limido A, Spotti D, Locatelli F (2001) Parathyroidectomy in patients on renal replacement therapy: an epidemiologic study. J Am Soc Nephrol 12:1242–1248PubMedGoogle Scholar
  28. Mittman N, Desiraju B, Meyer KB, Chattopadhyay J, Avram MM (2010) Treatment of secondary hyperparathyroidism in ESRD: a 2-year, single-center crossover study. Kidney Int Suppl:S33–S36.  https://doi.org/10.1038/ki.2010.191 CrossRefGoogle Scholar
  29. Montagna P (2005) Fatal familial insomnia: a model disease in sleep physiopathology. Sleep Med Rev 9:339–353.  https://doi.org/10.1016/j.smrv.2005.02.001 CrossRefPubMedGoogle Scholar
  30. Pai M-F, Hsu S-P, Yang S-Y, Ho T-I, Lai C-F, Peng Y-S (2007) Sleep disturbance in chronic hemodialysis patients: the impact of depression and Anemia. Ren Fail 29:673–677.  https://doi.org/10.1080/08860220701459642 CrossRefPubMedGoogle Scholar
  31. Perani D, Cortelli P, Lucignani G, Montagna P, Tinuper P, Gallassi R, Gambetti P, Lenzi GL, Lugaresi E, Fazio F (1993) [18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions. Neurology 43:2565–2569CrossRefPubMedGoogle Scholar
  32. Perl J, Unruh ML, Chan CT (2006) Sleep disorders in end-stage renal disease: 'Markers of inadequate dialysis'? Kidney Int 70:1687–1693.  https://doi.org/10.1038/sj.ki.5001791 CrossRefPubMedGoogle Scholar
  33. Roger SD, Harris DC, Stewart JH (1991) Possible relation between restless legs and anaemia in renal dialysis patients. Lancet 337:1551CrossRefPubMedGoogle Scholar
  34. Roman SA, Sosa JA, Pietrzak RH, Snyder PJ, Thomas DC, Udelsman R, Mayes L (2011) The effects of serum calcium and parathyroid hormone changes on psychological and cognitive function in patients undergoing parathyroidectomy for primary hyperparathyroidism. Ann Surg 253:131–137.  https://doi.org/10.1097/SLA.0b013e3181f66720 CrossRefPubMedGoogle Scholar
  35. Sabbatini M, Minale B, Crispo A, Pisani A, Ragosta A, Esposito R, Cesaro A, Cianciaruso B, Andreucci VE (2002) Insomnia in maintenance haemodialysis patients. Nephrol Dial Transplant 17:852–856CrossRefPubMedGoogle Scholar
  36. Sasaki O, Hattori N, Nakahama H, Inoue N, Nakamura S, Inenaga T, Kohno S, Sawada T, Kawano Y (2006) Positive correlations between cerebral choline and renal dysfunction in chronic renal failure. Neuroradiology 48:300–306CrossRefPubMedGoogle Scholar
  37. Scholtz CL, Swash M, Gray A, Kogeorgos J, Marsh F (1987) Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminum toxicity. Clin Neuropathol 6:93–97PubMedGoogle Scholar
  38. Silver J, Kilav R, Naveh-Many T (2002) Mechanisms of secondary hyperparathyroidism. Am J Physiol Renal Physiol 283:F367–F376.  https://doi.org/10.1152/ajprenal.00061.2002 CrossRefPubMedGoogle Scholar
  39. Smogorzewski MJ (2001) Central nervous dysfunction in uremia. Am J Kidney Dis 38:S122–S128CrossRefPubMedGoogle Scholar
  40. Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685CrossRefPubMedGoogle Scholar
  41. The International Restless Legs Syndrome Study G (2003) Validation of the international restless legs syndrome study group rating scale for restless legs syndrome. Sleep Med 4:121–132.  https://doi.org/10.1016/S1389-9457(02)00258-7 CrossRefGoogle Scholar
  42. Unruh ML, Levey AS, D'Ambrosio C, Fink NE, Powe NR, Meyer KB (2004) Restless legs symptoms among incident dialysis patients: association with lower quality of life and shorter survival. Am J Kidney Dis 43:900–909CrossRefPubMedGoogle Scholar
  43. von Krosigk M, Bal T, McCormick DA (1993) Cellular mechanisms of a synchronized oscillation in the thalamus. Science 261:361–364CrossRefGoogle Scholar
  44. Walker S, Fine A, Kryger MH (1995) Sleep complaints are common in a dialysis unit. Am J Kidney Dis 26:751–756CrossRefPubMedGoogle Scholar
  45. Walker MD, Fleischer J, Rundek T, McMahon DJ, Homma S, Sacco R, Silverberg SJ (2009) Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab 94:3849–3856.  https://doi.org/10.1210/jc.2009-1086 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Watanabe K, Watanabe T, Nakayama M (2014) Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology 44:184–193.  https://doi.org/10.1016/j.neuro.2014.06.014 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical ImagingFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Department of Magnetic Resonance ImagingBaoji Hospital of Traditional Chinese MedicineBaojiChina
  3. 3.Department of Medical ImagingNO. 215 Hospital of Shaanxi Nuclear IndustryXianyangChina
  4. 4.Department of NephrologyFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  5. 5.Center for Brain Imaging, School of Life Science and TechnologyXidian UniversityXi’anPeople’s Republic of China

Personalised recommendations