The changes of whole brain functional connectivity in hemodialysis (HD) patients with end-stage renal disease (ESRD) are still unclear, which may be associated with multiple factors, such as elevated neurotoxins, anemia, and side effects of hemodialysis. Resting-state functional magnetic resonance imaging (rs-fMRI) data of 71 patients (43 males, 28 females; mean age, 33.4 ± 9.4 years) and 43 age- and gender-matched healthy volunteers (29 males, 14 females; mean age, 30.6 ± 8.8 years) were acquired. Neuropsychological tests including number connection test type A (NCT-A), digit symbol test (DST), line-tracing test (LTT), serial-dotting test (SDT), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to evaluate cognitive and psychiatric conditions in all subjects. Blood biochemistry tests including serum creatinine levels, blood urea, hematocrit, and Ca2+ level were taken in HD patients. Forty-two connections significantly different between HD patients with ESRD and controls were found (all P < 0.05, Bonferroni corrected) and identified as connectivities of interests (COIs), among which 39 connections (92.9 %) were markedly decreased in patients. Of the 39 weaker connections, 24 were related to the frontal lobe regions. Widespread weakening of cortical and subcortical network connectivity in ESRD patients was more directly related with neuropsychological impairments and anemia rather than serum creatinine level, blood urea and dialysis duration. In particular, impairments in the medial prefrontal lobe could play an important role in mediating psychological dysfunctions.
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Conflict of interest
The authors disclose no conflicts.
Supported by grants from National Natural Science Foundation of China (grant No. 81101039 to G.Z., grants No. 81322020, 81230032, and 81171313 to L.J.Z.), the Program for New Century Excellent Talents in the University (NCET-12-0260 to L.J.Z.), and China Postdoctoral Science Foundation of Jiangsu Province (grant No. 1002083C to G.Z.).
Bajaj JS, Wade JB, Sanyal AJ (2009) Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology 50(6):2014–2021PubMedCrossRefGoogle Scholar
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 57(1):289–300Google Scholar
Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34(4):537–541PubMedCrossRefGoogle Scholar
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(3):353–363PubMedCrossRefGoogle Scholar
Chou MC, Hsieh TJ, Lin YL, et al. (2013) Widespread white matter alterations in patients with end-stage renal disease: A voxelwise diffusion tensor imaging study. AJNR Am J Neuroradiol. Jun 20. [Epub ahead of print] PMID:23788598Google Scholar
Collins AJ, Foley RN, Herzog C et al (2011) US renal data system 2010 annual data report. Am J Kidney Dis 57(A8):e1–e526Google Scholar
Elias MF, Elias PK, Seliger SL, Narsipur SS, Dore GA, Robbins MA (2009) Chronic kidney disease, creatinine and cognitive functioning. Nephrol Dial Transplant 24(8):2446–2452PubMedCentralPubMedCrossRefGoogle Scholar
Fazekas G, Fazekas F, Schmidt R et al (1996) Pattern of cerebral blood flow and cognition in patients undergoing chronic haemodialysis treatment. Nucl Med Commun 17(7):603–608PubMedCrossRefGoogle Scholar
Ferenci P, Lockwood A, Mullen K et al (1998) Hepatic encephalopathy–definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna. Hepatology 35(3):716–721CrossRefGoogle Scholar
Hsieh TJ, Chang JM, Chuang HY et al (2009) End-stage renal disease: in vivo diffusion-tensor imaging of silent white matter damage. Radiology 252(2):518–525PubMedCrossRefGoogle Scholar
Hsu CY, McCulloch CE, Curhan GC (2002) Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol 13(2):504–510PubMedGoogle Scholar
Kamata T, Hishida A, Takita T et al (2000) Morphologic abnormalities in the brain of chronically hemodialyzed patients without cerebrovascular disease. Am J Nephrol 20(1):27–31PubMedCrossRefGoogle Scholar
Kim HS, Park JW, Bai DS et al (2011) Diffusion tensor imaging findings in neurologically asymptomatic patients with end stage renal disease. Neuro Rehabil 29(1):111–116Google Scholar
Kimmel PL, Cukor D, Cohen SD et al (2007) Depression in end-stage renal disease patients: a critical review. Adv Chron Kidney Dis 14(4):328–334CrossRefGoogle Scholar
Kirschbaum B (2004) Effect of high bicarbonate hemodialysis on ionized calcium and risk of metastatic calcification. Clin Chim Acta 343(1–2):231–236PubMedCrossRefGoogle Scholar
Liang X, Wen J, Ni L et al (2013) Altered pattern of spontaneous brain activity in the patients with end-stage renal disease: a resting-state functional MRI study with regional homogeneity analysis. PLoS One 8(8):e71507PubMedCentralPubMedCrossRefGoogle Scholar
Madan P, Kalra OP, Agarwal S et al (2007) Cognitive impairment in chronic kidney disease. Nephrol Dial Transplant 22(2):440–444PubMedCrossRefGoogle Scholar
Madhavan D, Heinrichs-Graham E, Wilson TW (2013) Whole-brain functional connectivity increases with extended duration of focal epileptiform activity. Neurosci Lett 542:26–29PubMedCrossRefGoogle Scholar
Rocca MA, Absinta M, Moiola L et al (2010) Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis. Radiology 254(2):541–550PubMedCrossRefGoogle Scholar
Tzourio-Mazoyer N, Landeau B, Papathanassiou D et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15(1):273–289PubMedCrossRefGoogle Scholar
Zhang LJ, Zheng G, Zhang L et al (2012) Altered brain functional connectivity in patients with cirrhosis and minimal hepatic encephalopathy: a functional MR imaging study. Radiology 265(2):528–536PubMedCrossRefGoogle Scholar
Zhang LJ, Wen J, Ni L, et al. (2013) Predominant gray matter volume loss in patients with end-stage renal disease: a voxel-based morphometry study. Metab Brain Dis 28(4):647–654Google Scholar