尿毒症规律血液透析患者脑出血危险因素分析

doi:10.3969/j.issn.1004-583X.2022.01.003

摘要/Abstract

摘要：

目的探讨尿毒症规律血液透析患者脑出血发生的危险因素。方法回顾性分析2012年1月至2020年6月青岛大学附属医院及其附近医院收治的尿毒症规律血液透析发生脑出血患者(脑出血组)44例,随机选取同时段尿毒症规律血液透析未发生脑出血患者(对照组)224例,比较两组一般资料及实验室指标。采用独立样本t检验、χ²检验、Mann-Whitney U检验及Logistic回归分析处理数据,绘制危险因素列线图,建立临床预测模型。结果多因素Logistic回归分析结果显示,高血清钙、低血清钠、高白细胞计数、高日常血液透析时收缩压、脑出血事件前收缩压、既往高血压病史、既往脑血管事件史、原发病为多囊肾、日常应用华法林为尿毒症规律血液透析患者脑出血的独立危险因素;基于上述危险因素构建尿毒症规律血液透析患者脑出血发生风险的列线图预测模型,校正曲线提示模型准确度良好。结论高血清钙、低血清钠、高血白细胞计数、高日常血液透析时收缩压、脑出血事件前收缩压、既往高血压病史、既往脑血管事件史、原发病为多囊肾、日常应用华法林为尿毒症规律血液透析患者发生脑出血的独立危险因素,列线图对尿毒症规律血液透析患者发生脑出血的风险评估有一定的临床价值。

关键词: 尿毒症, 脑出血, 危险因素

Abstract:

Objective To explore the risk factors of cerebral hemorrhage in uremic patients on regular hemodialysis. Methods Totally 44 uremic patients with cerebral hemorrhage on regular hemodialysis (cerebral hemorrhage group) admitted to the Affiliated Hospital of Qingdao University and other surrounding hospitals from January 2012 to June 2020 were analyzed retrospectively, 224 uremic patients on regular hemodialysis without cerebral hemorrhage in the same period were randomly enrolled (control group). The general data and laboratory indicators between groups were analyzed. Data was addressed with independent sample t-test, chi-square test (χ² test), Mann-Whitney U-test and Logistic regression analysis, the nomogram for predicting factor was drawn to establish clinical prediction model. Results The results of multivariate logistics regression analysis showed that the independent risk factors for uremic patients with cerebral hemorrhage on regular hemodialysis were high serum serum calcium, low serum sodium, high white blood cell count, high systolic blood pressure on daily regular hemodialysis, systolic blood pressure before cerebral hemorrhage events, previous history of hypertension and cerebrovascular events, primary polycystic kidney disease, daily intervention by warfarin. Based on the above risk factors a nomogram for prediction model factor of risk of cerebral hemorrhage in patients with uremia on regular hemodialysis was established, and the correction curve showed good accuracy of the model. Conclusion The independent risk factors for uremic patients with cerebral hemorrhage on regular hemodialysis were high serum calcium, low serum sodium, high white blood cell count, high systolic blood pressure on daily regular hemodialysis, systolic blood pressure before cerebral hemorrhage events, previous history of hypertension and cerebrovascular events, primary polycystic kidney disease, daily intervention by warfarin, and the nomogram has certain clinical value for the risk assessment of uremic patients with cerebral hemorrhage on regular hemodialysis.

Key words: uremia, cerebral hemorrhage, risk factors

中图分类号:

R692.5

李文哲, 商进春, 李春梅, 田芬, 李君, 崔莉, 邢广群. 尿毒症规律血液透析患者脑出血危险因素分析[J]. 临床荟萃, 2022, 37(1): 20-25.

Li Wenzhe, Shang Jinchun, Li Chunmei, Tian Fen, Li Jun, Cui Li, Xing Guangqun. Risk factors of cerebral hemorrhage in uremic patients on regular hemodialysis[J]. Clinical Focus, 2022, 37(1): 20-25.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.01.003

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I1/20

图/表 5

参考文献 25

[1]	Toyoda K, Ninomiya T. Stroke and cerebrovascular diseases in patients with chronic kidney disease[J]. Lancet Neurol, 2014, 13(8):823-833. doi: 10.1016/S1474-4422(14)70026-2 URL
[2]	Thomé FS, Sesso RC, Lopes AA, et al. Brazilian chronic dialysis survey 2017[J]. J Bras Nefrol, 2019, 41(2):208-214. doi: 10.1590/2175-8239-jbn-2018-0178 URL
[3]	Wakasugi M, Matsuo K, Kazama JJ, et al. Higher mortality due to intracerebral hemorrhage in dialysis patients: A comparison with the general population in Japan[J]. Ther Apher Dial, 2015, 19(1):45-49. doi: 10.1111/1744-9987.12192 URL
[4]	Lee M, Saver JL, Chang KH, et al. Low glomerular filtration rate and risk of stroke: Meta-analysis[J]. BMJ, 2010, 341:c4249. doi: 10.1136/bmj.c4249 URL
[5]	Cherng YG, Lin CS, Shih CC, et al. Stroke risk and outcomes in patients with chronic kidney disease or end-stage renal disease: Two nationwide studies[J]. PLoS One, 2018, 13(1):e0191155.
[6]	Dad T, Weiner DE. Stroke and chronic kidney disease: Epidemiology, pathogenesis, and management across kidney disease stages[J]. Semin Nephrol, 2015, 35(4):311-322. doi: 10.1016/j.semnephrol.2015.06.003 URL
[7]	Tonelli M, Karumanchi SA, Thadhani R. Epidemiology and mechanisms of uremia-related cardiovascular disease[J]. Circulation, 2016, 133(5):518-536. doi: 10.1161/CIRCULATIONAHA.115.018713 URL
[8]	Saran R, Robinson B, Abbott KC, et al. Erratum regarding “US Renal Data System 2017 Annual Data Report: Epidemiology of Kidney Disease in the United States”[J]. Am J Kidney Dis, 2018, 71(4):501. doi: 10.1053/j.ajkd.2018.03.001 URL
[9]	Arnold J, Sims D, Ferro CJ. Modulation of stroke risk in chronic kidney disease[J]. Clin Kidney J, 2016, 9(1):29-38. doi: 10.1093/ckj/sfv136 pmid: 26798458
[10]	Kitamura M, Tateishi Y, Sato S, et al. Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis[J]. BMC Nephrol, 2019, 20(1):210. doi: 10.1186/s12882-019-1400-4 pmid: 31174486
[11]	Howarth C. The contribution of astrocytes to the regulation of cerebral blood flow[J]. Front Neurosci, 2014, 8:103.
[12]	Shroff RC, McNair R, Skepper JN, et al. Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification[J]. J Am Soc Nephrol, 2010, 21(1):103-112. doi: 10.1681/ASN.2009060640 URL
[13]	Beierwaltes WH. The role of calcium in the regulation of renin secretion[J]. Am J Physiol Renal Physiol, 2010, 298(1):F1-F11. doi: 10.1152/ajprenal.00143.2009 URL
[14]	Smajilovic S, Yano S, Jabbari R, et al. The calcium-sensing receptor and calcimimetics in blood pressure modulation[J]. Br J Pharmacol, 2011, 164(3):884-893. doi: 10.1111/bph.2011.164.issue-3 URL
[15]	Eisner DA, Caldwell JL, Kistamás K, Trafford AW. Calcium and excitation-contraction coupling in the heart[J]. Circ Res, 2017, 121(2):181-195. doi: 10.1161/CIRCRESAHA.117.310230 pmid: 28684623
[16]	O'Neill WC. Targeting serum calcium in chronic kidney disease and end-stage renal disease: Is normal too high?[J]. Kidney Int, 2016, 89(1):40-45. doi: 10.1016/j.kint.2015.10.001 URL
[17]	Abdullahi W, Tripathi D, Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection[J]. Am J Physiol Cell Physiol, 2018, 315(3):C343-C356. doi: 10.1152/ajpcell.00095.2018 URL
[18]	Cortina G, Hansford JR, Duke T. Central diabetes insipidus and cisplatin-induced renal salt wasting syndrome: A challenging combination[J]. Pediatr Blood Cancer, 2016, 63(5):925-927. doi: 10.1002/pbc.25910 pmid: 26928867
[19]	刘颖, 张艳, 莫颖. 对接受维持性血液透析患者预后影响因素的研究[J]. 当代医药论丛, 2020, 18(10):103-104.
[20]	Cohen G, Raupachova J, Borchhardt K, et al. Cinacalcet effect on polymorphonuclear leucocytes of kidney transplant patients[J]. Eur J Clin Invest 43 (5):476-482. doi: 10.1111/eci.2013.43.issue-5 URL
[21]	Yamada S, Tsuruya K, Taniguchi M, et al. Association between serum phosphate levels and stroke risk in patients undergoing hemodialysis: The Q-cohort study[J]. Stroke, 2016, 47(9):2189-2196. doi: 10.1161/STROKEAHA.116.013195 URL
[22]	Naganuma T, Takemoto Y, Shoji T, et al. Cerebral microbleeds predict intracerebral hemorrhage in hemodialysis patients[J]. Stroke, 2015, 46(8):2107-2112. doi: 10.1161/STROKEAHA.115.009324 URL
[23]	Wilkinson DA, Heung M, Deol A, et al. Cerebral aneurysms in autosomal dominant polycystic kidney disease: A comparison of management approaches[J]. Neurosurgery, 2019 84(6):E352-E361. doi: 10.1093/neuros/nyy336
[24]	肖文颖. 多囊肾伴高血压1例[J]. 中西医结合心血管病电子杂志, 2015, 3(21):197-198.
[25]	Xiao M, Li Q, Feng H, et al. Neural vascular mechanism for the cerebral blood flow autoregulation after hemorrhagic stroke[J]. Neural Plast, 2017, 2017:5819514.

项目	脑出血组(n=44)	对照组(n=224)	统计值	P值
性别[例(%)]
男女	26(59.1) 18(40.9)	133(59.4) 91(40.6)	χ²=0.001	0.972
年龄(岁)	54(45, 64)	54(43, 64)	Z=-0.535	0.593
高血压病史[例(%)]
是否	41(93.2) 3(6.8)	70(31.3) 154(68.7)	χ²=58.135	<0.05
脑出血事件前收缩压(mmHg)	184.810±24.081	147.400±19.887	t=-10.91	<0.05
脑出血事件前舒张压(mmHg)	103.930±14.608	82.780±13.349	t=-9.376	<0.05
日常血液透析时收缩压(mmHg)	159.120±22.343	146.970±20.056	t=-3.57	<0.05
日常血液透析时舒张压(mmHg)	88.910±13.425	83.130±13.106	t=-2.639	<0.05
糖尿病病史[例(%)]
是否	23(52.3) 21(47.7)	31(13.8) 193(86.2)	χ²=33.763	<0.05
脑血管事件史[例(%)]
是否	32(72.8) 12(27.2)	43(19.2) 181(80.8)	χ²=52.291	<0.05
透析时肝素使用[例(%)]
是否	40(90.9) 4(9.1)	216(96.4) 8(3.6)	χ²=2.619	0.106
原发病为多囊肾[例(%)]
是否	4(9.1) 40(90.9)	2(0.9) 222(99.1)	χ²=11.293	<0.05
初始透析方式是否为血液透析[例(%)]
是否	40(90.9) 4(9.1)	213(95.1) 11(4.9)	χ²=1.216	0.270
日常应用华法林[例(%)]
是否	18(40.9) 26(59.1)	5(2.2) 219(97.8)	χ²=70.121	<0.05
日常应用阿司匹林[例(%)]
是否	12(27.3) 32(72.7)	89(39.7) 135(60.3)	χ²=2.431	0.119

项目	脑出血组(n=44)	对照组(n=224)	统计值	P值
性别[例(%)]
男女	26(59.1) 18(40.9)	133(59.4) 91(40.6)	χ²=0.001	0.972
年龄(岁)	54(45, 64)	54(43, 64)	Z=-0.535	0.593
高血压病史[例(%)]
是否	41(93.2) 3(6.8)	70(31.3) 154(68.7)	χ²=58.135	<0.05
脑出血事件前收缩压(mmHg)	184.810±24.081	147.400±19.887	t=-10.91	<0.05
脑出血事件前舒张压(mmHg)	103.930±14.608	82.780±13.349	t=-9.376	<0.05
日常血液透析时收缩压(mmHg)	159.120±22.343	146.970±20.056	t=-3.57	<0.05
日常血液透析时舒张压(mmHg)	88.910±13.425	83.130±13.106	t=-2.639	<0.05
糖尿病病史[例(%)]
是否	23(52.3) 21(47.7)	31(13.8) 193(86.2)	χ²=33.763	<0.05
脑血管事件史[例(%)]
是否	32(72.8) 12(27.2)	43(19.2) 181(80.8)	χ²=52.291	<0.05
透析时肝素使用[例(%)]
是否	40(90.9) 4(9.1)	216(96.4) 8(3.6)	χ²=2.619	0.106
原发病为多囊肾[例(%)]
是否	4(9.1) 40(90.9)	2(0.9) 222(99.1)	χ²=11.293	<0.05
初始透析方式是否为血液透析[例(%)]
是否	40(90.9) 4(9.1)	213(95.1) 11(4.9)	χ²=1.216	0.270
日常应用华法林[例(%)]
是否	18(40.9) 26(59.1)	5(2.2) 219(97.8)	χ²=70.121	<0.05
日常应用阿司匹林[例(%)]
是否	12(27.3) 32(72.7)	89(39.7) 135(60.3)	χ²=2.431	0.119

项目	脑出血组(n=44)	对照组(n=244)	统计值	P值
血清钠(mmol/L)	136.553±6.230	141.487±3.498	t=5.043	<0.05
血清钙(mmol/L)	2.244±0.330	1.958±0.272	t=-6.075	<0.05
血清磷(mmol/L)	1.560(1.333,2.225)	1.920(1.578,2.283)	Z=-1.977	0.058
血清钾(mmol/L)	4.867±0.850	4.524±0.769	t=-2.636	<0.05
血肌酐(μmol/L)	760.819±299.471	803.496±254.091	t=0.980	0.328
尿素氮(mmol/L)	25.410(17.300,37.770)	28.220(21.625,34.935)	Z=-0.694	0.488
谷丙转氨酶(U/L)	14.700(10.500,20.400)	12.100(7.850,18.950)	Z=-2.113	<0.05
谷草转氨酶(U/L)	14.800(11.400,21.600)	13.000(10.150,17.250)	Z=-1.780	0.075
血清白蛋白(g/L)	33.900 (28.300,38.000)	34.900(29.950,39.350)	Z=-0.963	0.335
血清总蛋白(g/L)	59.345±9.146	60.651±8.943	t=0.874	0.383
TG(mmol/L)	1.890(1.410,2.860)	1.360(1.020,1.820)	Z=-4.437	<0.05
TC(mmol/L)	4.570(3.730,5.400)	4.040(3.435,4.980)	Z=-1.930	0.054
LDL-C(mmol/L)	2.470(1.980,3.340)	2.270(1.825,2.845)	Z=-2.251	<0.05
HDL-C(mmol/L)	1.100(0.970,1.270)	1.070(0.955,1.320)	Z=-0.216	0.829
血糖(mmol/L)	5.945(4.893,8.423)	4.870(4.283,6.115)	Z=-2.866	<0.05
D-二聚体(μg/L)	720.000(340.000,1180.000)	380.000(230.000,577.500)	Z=-4.945	<0.05
活化部分凝血活酶时间(s)	32.600(28.200,34.400)	31.150(28.125,34.000)	Z=-1.063	0.268
凝血酶原时间(s)	12.100(11.400,13.400)	11.800(10.700,12.675)	Z=-1.670	0.095
CRP(mg/L)	8.900(2.200,20.000)	2.510(0.515,9.460)	Z=-4.325	<0.05
PCT(ng/ml)	0.410(0.175,2.010)	0.270(0.070,0.600)	Z=-2.675	<0.05
白细胞计数(×10⁹/L)	7.445(5.550,9.863)	5.890(5.005,7.180)	Z=-3.496	<0.05
中性粒细胞(×10⁹/L)	5.530(3.638,6.590)	4.200(3.270,5.230)	Z=-3.049	<0.05
血小板计数(×10⁹/L)	178.175±67.057	186.349±68.026	t=0.702	0.483
血红蛋白(g/L)	98.000(75.000,113.000)	88.000(74.000,105.000)	Z=-1.945	0.052
BNP(pg/ml)	604.400(248.075,1558.625)	236.800(104.700,495.500)	Z=-3.873	<0.05
甲状旁腺素(pmol/L)	171.300(95.620,288.300)	239.700(134.100,355.100)	Z=-1.841	0.066
尿酸(μmol/L)	404.663±111.767	414.434±137.255	t=0.425	0.671
血沉(mm/h)	30.000(11.700,94.800)	20.900(13.575,34.425)	Z=-1.077	0.593

项目	脑出血组(n=44)	对照组(n=244)	统计值	P值
血清钠(mmol/L)	136.553±6.230	141.487±3.498	t=5.043	<0.05
血清钙(mmol/L)	2.244±0.330	1.958±0.272	t=-6.075	<0.05
血清磷(mmol/L)	1.560(1.333,2.225)	1.920(1.578,2.283)	Z=-1.977	0.058
血清钾(mmol/L)	4.867±0.850	4.524±0.769	t=-2.636	<0.05
血肌酐(μmol/L)	760.819±299.471	803.496±254.091	t=0.980	0.328
尿素氮(mmol/L)	25.410(17.300,37.770)	28.220(21.625,34.935)	Z=-0.694	0.488
谷丙转氨酶(U/L)	14.700(10.500,20.400)	12.100(7.850,18.950)	Z=-2.113	<0.05
谷草转氨酶(U/L)	14.800(11.400,21.600)	13.000(10.150,17.250)	Z=-1.780	0.075
血清白蛋白(g/L)	33.900 (28.300,38.000)	34.900(29.950,39.350)	Z=-0.963	0.335
血清总蛋白(g/L)	59.345±9.146	60.651±8.943	t=0.874	0.383
TG(mmol/L)	1.890(1.410,2.860)	1.360(1.020,1.820)	Z=-4.437	<0.05
TC(mmol/L)	4.570(3.730,5.400)	4.040(3.435,4.980)	Z=-1.930	0.054
LDL-C(mmol/L)	2.470(1.980,3.340)	2.270(1.825,2.845)	Z=-2.251	<0.05
HDL-C(mmol/L)	1.100(0.970,1.270)	1.070(0.955,1.320)	Z=-0.216	0.829
血糖(mmol/L)	5.945(4.893,8.423)	4.870(4.283,6.115)	Z=-2.866	<0.05
D-二聚体(μg/L)	720.000(340.000,1180.000)	380.000(230.000,577.500)	Z=-4.945	<0.05
活化部分凝血活酶时间(s)	32.600(28.200,34.400)	31.150(28.125,34.000)	Z=-1.063	0.268
凝血酶原时间(s)	12.100(11.400,13.400)	11.800(10.700,12.675)	Z=-1.670	0.095
CRP(mg/L)	8.900(2.200,20.000)	2.510(0.515,9.460)	Z=-4.325	<0.05
PCT(ng/ml)	0.410(0.175,2.010)	0.270(0.070,0.600)	Z=-2.675	<0.05
白细胞计数(×10⁹/L)	7.445(5.550,9.863)	5.890(5.005,7.180)	Z=-3.496	<0.05
中性粒细胞(×10⁹/L)	5.530(3.638,6.590)	4.200(3.270,5.230)	Z=-3.049	<0.05
血小板计数(×10⁹/L)	178.175±67.057	186.349±68.026	t=0.702	0.483
血红蛋白(g/L)	98.000(75.000,113.000)	88.000(74.000,105.000)	Z=-1.945	0.052
BNP(pg/ml)	604.400(248.075,1558.625)	236.800(104.700,495.500)	Z=-3.873	<0.05
甲状旁腺素(pmol/L)	171.300(95.620,288.300)	239.700(134.100,355.100)	Z=-1.841	0.066
尿酸(μmol/L)	404.663±111.767	414.434±137.255	t=0.425	0.671
血沉(mm/h)	30.000(11.700,94.800)	20.900(13.575,34.425)	Z=-1.077	0.593

因素	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
因素	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
脑出血事件前收缩压	3.206	0.729	4.40	<0.01	24.667	5.907	103.020
日常血液透析时收缩压	2.818	0.850	3.32	<0.01	16.746	3.165	88.615
血清钠	-0.217	0.057	-3.83	<0.01	0.334	0.191	0.585
血清钙	3.432	0.874	3.93	<0.01	3.212	1.795	5.749
D-二聚体	0.002	0.001	3.51	<0.01	2.216	1.422	3.453
白细胞计数	0.238	0.086	2.78	0.005	1.792	1.188	2.702
既往高血压病史	3.010	0.869	3.46	<0.01	20.279	3.690	111.440
既往脑血管事件史	1.855	0.636	2.92	0.004	6.393	1.837	22.244
原发病为多囊肾	2.416	0.950	2.54	0.011	11.204	1.740	72.162
日常应用华法林	3.269	0.904	3.62	<0.01	26.280	4.472	154.430