目的 探讨持续非卧床腹膜透析(continuous ambulatory peritoneal dialysis, CAPD)患者高磷血症与认知障碍之间的相关性。方法 纳入河北医科大学第二医院肾内科2021年1月至2022年12月长期规律门诊随访CAPD患者。采用蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA) 评估患者整体认知功能;通过测试A (trail-making test forms A, TA)评估患者执行功能。采用SPSS26.0进行统计处理。结果 312例CAPD患者认知障碍患病率为36.9%。单因素相关性分析显示,高磷血症(OR=2.333,95%CI 1.456~3.736,P<0.001)、年龄(OR=0.830,95%CI 1.076~1.135,P<0.001)与整体认知功能显著相关。血清白蛋白(OR=0.869,95%CI 0.770~0.982,P=0.024)和年龄(OR=1.073,95%CI 1.024~1.124,P=0.003)与执行功能相关。血钙(OR=0.218,95%CI 0.048~0.999,P=0.050)、iPTH(OR=1.000,95%CI 0.999~1.001,P=0.484)与整体认知功能无显著相关性。多因素回归分析结果显示,目的 探讨持续性非卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)患者高磷血症与认知障碍之间的相关性。 方法 纳入河北医科大学第二医院肾内科2021年1月—2022年12月长期规律门诊随访的CAPD患者。采用蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)评估患者整体认知功能;通过测试A(trail-making test forms A,TA)评估患者执行功能。采用SPSS 26.0进行统计处理。 结果 312例CAPD患者认知障碍患病率为36.9%。单因素相关性分析显示:高磷血症(OR=2.333,95% CI:1.456~3.736,P<0.001)、年龄(OR=0.830,95% CI:1.076~1.135,P<0.001)与整体认知功能相关。血清白蛋白(OR=0.869,95% CI:0.770~0.982,P=0.024)和年龄(OR=1.073,95% CI:1.024~1.124,P=0.003)与执行功能相关。血钙(OR=0.218,95% CI:0.048~0.999,P=0.050)、全段甲状旁腺激素(OR=1.000,95% CI:0.999~1.001,P=0.484)与整体认知功能无显著相关性。多因素回归分析结果显示:对人口学、临床及实验室混杂因素进行校正后,高磷血症仍与认知障碍相关(95% CI:3.272~17.741,P<0.001),高磷血症的CAPD患者认知障碍的发生率为非高磷血症患者的7.62倍。ROC曲线结果显示:当血磷取值为1.66时,约登指数最大值为0.30,灵敏度为75.7%,特异度为54.1%。 结论 在CAPD患者中,血磷水平影响患者的整体认知,高磷血症是腹膜透析患者认知障碍的独立危险因素,血磷水平大于1.66 mmol/L明显增加患者认知障碍的风险。
Objective To investigate the association between hyperphosphatemia and cognitive impairment in patients on continuous ambulatory peritoneal dialysis (CAPD). Methods This is a single-centered study recruited a total of 312 CAPD patients from the Second Hospital of Hebei Medical University in the period of January 2021 to December 2022. Their general cognitive function was examined using the Montreal Cognitive Assessment (MoCA), and their executive function was assessed by Test A (Trail-Making Test forms A, TA). Results were statistically processed by SPSS 26.0. Results ①Among the 312 CAPD patients, the prevalence of cognitive impairment was 36.9%. ②Univariate correlation analysis showed that hyperphosphatemia (OR=2.333, 95% CI:1.456~3.736, P<0.001) and age (OR=0.830, 95% CI:1.076~1.135, P<0.001) were correlated with general cognitive function, and serum albumin (OR=0.869, 95% CI:0.770~0.982, P=0.024) and age (OR=1.073, 95% CI:1.024~1.124, P=0.003) were correlated with executive function. There were no significant correlation between serum levels of calcium (OR=0.218, 95% CI:0.048~0.999, P=0.050) and iPTH (OR=1.000, 95% CI:0.999~1.001, P=0.484) and general cognitive and executive functions. ③Multivariate regression analysis suggested that hyperphosphatemia was significantly associated with cognitive impairment (95% CI:3.272~17.741, P<0.001) after adjustments for demographic, clinical and laboratory confounding factors. The incidence of cognitive impairment in CAPD patients with hyperphosphatemia was 7.62 times higher than that in the patients without hyperphosphatemia. ④ ROC curve indicated that when blood phosphorus was set at 1.66mmol/L, the maximum value of Youdon index was 0.30, the sensitivity was 75.7%, and the specificity was 54.10%. Conclusions In CAPD patients, serum phosphorus level affects general cognition of the patients, and hyperphosphatemia is an independent risk factor for cognitive impairment in CAPD patients. If serum phosphorus level increases to >1.66 mmol/L, the risk of cognitive impairment increases significantly.
[1] 葛均波等,内科学第9版[M],北京,人民卫生出版社,2019,518-519.
[2] Coresh J,Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United State[J]. JAMA. 2007;298(17):2038-2047.
[3] Griva K, Stygall J, Hankins M , et al. Cognitive impairment and 7-year mortality in dialysis patients[J]. Am J Kidney Dis.2010;56(4):693-703.
[4] Kalirao P, Pederson S, Foley RN, et al. Cognitive impairment in peritoneal dialysis patients[J]. Am j Kidney Dis.2011; 57(4): 612-620.
[5] Kurella M, Chertow GM, Luan J, et al. Cognitive impairment in chronic kidney disease[J]. J Am Geriatr Soc.2004;52(11): 1863-1869.
[6] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders(DSM-5) [M]. American Psychiatric Pub;2013.
[7] Longfei Jia, Yifeng Du, Lancet Public Health[J] 2020 Dec;5(12):e661-e671.
[8] Griva K, Stygall J, Hankins M, Davenport A, et al. Cognitive impairment and 7-year mortality in dialysis patients[J]. Am J Kidney Dis 56: 693–703, 2010
[9] Chunyan Yi, Jianxiong Lin, Sci Rep [J]. 2018 Nov 23;8(1):17305.
[10] Ilianna Lourida,Jo Thompson-Coon, PLoS One[J].2015 May 26; 10(5): e0127574.
[11] Wei Ling Lau1&BrankoN. Huisa2, Transl Stroke Res[J], 2017 Feb; 8(1): 67-76.
[12] 耿明慧,黎煜妍,维持性血液透析患者钙磷代谢紊乱与认知障碍的关系[J], 临床肾脏病杂志,2022,第22卷第9期.
[13] T. M. Liew, L. Feng, Q. Gao, et al. Diagnostic utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: major and mild neurocognitive disorders[J]. J Am Med Dir Assoc 16, 144-148(2015).
[14] Y. H. Zhang et al., Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study[J]. Am J Kidney Dis 72, 691-700(2018).
[15] Xu R, Han QF, Zhu TY, et al. Impact of individual and environmental socioeconomic status on peritoneal dialysis outcomes: A retrospective multicenter cohort study[J]. PLoS One 7: e50766, 2012.
[16] 国家肾脏疾病临床医学研究中心,中国慢性肾脏病矿物质和骨异常诊治指南概要[J],肾脏病与透析肾移植杂志, 2019年02月, 第28卷 第1期.
[17] Bugnicourt JM, Godefroy O, Chillon JM, et al, Cognitive disorders and dementia in CKD: the neglected kidney-brain axis[J]. J Am Soc Nephrol. 2013;24:353–63.
[18] Kalirao P, Pederson S, Foley RN, et al. Cognitive impairment in peritoneal dialysis patients[J]. Am J Kidney Dis 57: 612–620, 2011.
[19] D. Asaoka et al., Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial[J]. J Alzheimers Dis 88, 75-95(2022).
[20] L. A. Zilliox, K. Chadrasekaran, J. Y. Kwan, et al. Diabetes and Cognitive Impairment[J]. Current Diabetes Reports 16, (2016).
[21] Seeley WW. Anterior insula degeneration in frontotemporal de-
[22] mentia. Brain Struct Funct[J]. 2010;214(5–6):465–75.
[23] Q. Zhang, Y. Wu, T. Han, et al. Changes in Cognitive Function and Risk Factors for Cognitive Impairment of the Elderly in China[J]: 2005–2014. International Journal of Environmental Research and Public Health 16, (2019).
[24] H. Karakizlis, K. Bohl, J. Ziemek, et al. Assessment of cognitive impairment and related risk factors in hemodialysis patients[J]. Journal of Nephrology 35, 931-942(2021).
[25] X. Tian et al., Cognitive Dysfunction and Its Risk Factors in Patients Undergoing Maintenance Hemodialysis[J]. Neuropsychiatric Disease and Treatment Volume 18, 2759-2769(2022).
[26] N. Das, J. Ren, J. Spence, et al. Phosphate Brain Energy Metabolism and Cognition in Alzheimer's Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil(31)Phosphorus Magnetic Resonance Spectroscopy at 7Tesla[J]. Front Neurosci 15, 641739(2021).
[27] N. Das, J. Ren, J. S. Spence, et al. Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment[J]. Frontiers in Aging Neuroscience 12, (2020).
[28] W. Lv, C. Cui, Z. Wang, et al.A High Serum Phosphate and Calcium-Phosphate Product Is Associated With Cerebral Small Vascular Disease in Patients With Stroke: A Real-World Study[J]. Front Nutr 9, 801667(2022).
[29] Reynolds JL, Joannides AJ, Skepper JN, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD[J]. J AmSoc Nephrol.(2004) 15:2857–67.
[30] Rroji, M.; Figurek, A.;Viggiano, D.; et al. Phosphate in the Context ofCognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease[J]. Int. JMol. Sci. 2022, 23, 7362.
[31] Tonelli, M.; Sacks, F.; Pfeffer, M.; et al. Relation Between Serum Phosphate Level and Cardiovascular Event Rate in People With Coronary Disease[J]. Circulation 2005, 112, 2627–2633.
[32] Bugnicourt, J.-M.; Chillon, J.-M.; Massy, Z.A.; et al. High Prevalence of Intracranial Artery Calcification in Stroke Patients with CKD: A Retrospective Study[J]. Clin. J. Am. Soc. Nephrol. 2009, 4, 284–290.
[33] Bartstra, J.W.; Beukel, T.C.V.D.; et al. Intracranial Arterial Calcification: Prevalence, Risk Factors, and Consequences[J]. J. Am. Coll. Cardiol. 2020, 76, 1595–1604.
[34] LV W, CUI C, WANG Z, et al. A High Serum Phosphate and Calcium-Phosphate Product Is Associated With Cerebral Small Vascular Disease in Patients With Stroke: A Real-World Study [J]. Front Nutr, 2022, 9: 801667.
[35] Lee, S.J.; Lee, I.-K.; Jeon, J.-H. Vascular Calcification—New Insights into Its Mechanism[J]. Int. J. Mol. Sci. 2020, 21, 2685.
[36] Cozzolino, M.; Ciceri, P.; Galassi, A.; et al. The Key Role of Phosphate on Vascular Calcification[J]. Toxins 2019, 11, 213
[37] Shanahan, C.; Crouthamel, M.H.; Kapustin, A.; et al. Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate[J]. Circ. Res. 2011, 109, 697–711.
[38] Li, Z.; Wiernek, S.; Patterson, C.; et al. MicroRNA-21 mediates high phosphate-induced endothelial cell apoptosis[J]. Am. J. Physiol. Physiol. 2018, 315, C830–C838.