血清氨基末端脑钠肽前体水平初筛腹膜透析患者容量超负荷的价值

doi:10.16138/j.1673-6087.2023.03.005

摘要/Abstract

摘要：

目的: 探讨腹膜透析（peritoneal dialysis，PD）患者血清氨基末端脑钠肽前体（N-terminal pro-B natriuretic peptide，NT-proBNP）水平与患者水合状态、心功能指标的关系，并进一步分析影响PD患者NT-proBNP水平的因素。方法: 回顾性收集2019年5月—2022年1月在上海交通大学医学院附属瑞金医院PD中心随访的PD患者111例，根据多频生物电阻抗人体成分分析仪（body composition monitor，BCM）测定结果，按相对水合状态（relative hydration status，DHS），即超负荷水量（overhydration，OH）和细胞外水（extracellular water，ECW）比值，将其分为容量正常组（OH/ECW≤15%）与容量超负荷组（OH/ECW>15%）。比较2组患者血清NT-proBNP水平与水合状态关系，并进一步分析探讨影响NT-proBNP水平的相关因素。以BCM结果作为“金标准”，受试者操作特征曲线（receiver operator characteristic curve，ROC曲线）确定容量超负荷时NT-proBNP最佳阈值。并根据NT-proBNP进行分组，比较2组的临床资料。结果: 容量超负荷组和容量正常组在收缩压、尿量、总尿素清除指数（urea clearance index，Kt/V）、总肌酐清除率（creatinine clearance rate，CCr）、4 h透析液肌酐/血肌酐比值（dialysate to plasma ratio for urea at 4 hours，4hD/PCr）、降压药种类、利尿剂种类、血红蛋白、血清白蛋白、log₂（NT-proBNP）、室间隔厚度（interventricular septal thickness，IVST）、左室后壁厚度（left ventricular posterior wall thickness，LVPWT）、左房内径（left atrial diameter，LAD）、OH、TBW、ECW、OH/TBW、ECW/TBW、ECW/ICW方面差异有统计学意义（均P<0.05）。log₂（NT-proBNP）水平与收缩压、透析龄、超滤量、透析剂量、降压药分组、IVST、LVPWT、LAD、左心室收缩末期内径（left ventricular end-systolic dimension，LVESD）、左室舒张末期内径（left ventricular end-diastolic dimension，LVEDD）、OH、OH/ECW呈正相关（均P<0.05），与尿量、总Kt/V、总CCr、标准蛋白分解率（normalized protein catabolic rate，nPCR）、血红蛋白、血清白蛋白、左室射血分数（left ventricular ejection fraction，LVEF）呈负相关（均P<0.05）。NT-proBNP 4 896 ng/L可作为初筛容量超负荷的临界值，按此分组的2组患者收缩压、尿量、超滤量、总Kt/V、总CCr、IVST、LVPWT、OH/ECW指标差异有统计学意义（均P<0.05）。结论: PD患者NT-proBNP水平普遍升高，其大于4 896 ng/L提示容量超负荷，可作为初步判断PD患者容量超负荷的简易监测指标。

关键词: 腹膜透析, 氨基末端脑钠肽前体, 容量超负荷, 多频生物电阻抗法, 超声心动图

Abstract:

Objective To explore the relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and hydration status and cardiac function indexes in the patients receiving peritoneal dialysis(PD) treatment，and to further analyze the factors affecting the level of NT-proBNP. Methods A total of 111 patients with PD who were followed up in the PD Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from May 2019 to January 2022 were enrolled and the data was analyzed retrospectively. According to the results of multi-frequency bioelectrical impedance body composition monitor (BCM), relative hydration status (DHS), the ratio obtained through dividing extracellular water (ECW) by overhydration (OH), the patients were divided into normal volume group (OH/ECW≤15%) and overhydration group (OH/ECW>15%). The relationship between serum NT-proBNP level and hydration status in two groups was compared, and the related factors affecting the level of NT-proBNP were further analyzed and discussed. Using BCM result as the“gold standard”, the receiver operator characteristic curve(ROC curve) determined the optimal threshold of NT-proBNP as the capacity was overloaded. The patients were divided into two groups according to NT-proBNP and their clinical data were compared. Results The indexes including systolic blood pressure, urine volume, urea clearance index (Kt/V), creatinine clearance rate(CCr), dialysate to plasma ratio for urea at 4 hours(4hD/PCr), types of antihypertensive drugs, type of diuretic, hemoglobin, serum albumin, log₂(NT-proBNP), interventricular septal thickness (IVST), left ventricular posterior wall thickness(LVPWT), left atrial diameter(LAD), OH, TBW, ECW, OH/TBW, ECW/TBW and ECW/ICW were detected in volume overload group and normal volume group, and showed statistically significant (all P<0.05). log₂(NT-proBNP) level was correlated with systolic blood pressure, dialysis duration, ultrafiltration volume, dialysis dose, antihypertensive drug group, IVST, LVPWT, LAD, left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic dimension (LVEDD), OH, OH/ECW were positively correlated (all P<0.05). It was negatively correlated with urine volume, Kt/V, CCr, normalized protein catabolic rate (nPCR), hemoglobin, serum albumin and LVEF (all P<0.05). NT-proBNP 4 896 ng/L could be used as the critical value of initial screening capacity overload and was applied to divide the patients into two groups, and the systolic blood pressure, urine volume, ultrafiltration volume, Kt/V, CCr, IVST, LVPWT, OH/ECW indicators showed significant differences (all P<0.05) in two groups. Conclusions The level of NT-proBNP in PD patients is generally increased, and it indicates volume overload as its value is greater than 4 896 ng/L, which can be used as a simple monitoring index for the preliminary judgment of volume overload in PD patients.

Key words: Peritoneal dialysis, N-terminal pro-brain natriuretic peptide, Capacity overload, Multifrequency bioresistance method, Echocardiography

中图分类号:

R459.5

李花, 黄晓敏, 张春燕, 杜路, 任红, 徐天. 血清氨基末端脑钠肽前体水平初筛腹膜透析患者容量超负荷的价值[J]. 内科理论与实践, 2023, 18(03): 157-164.

LI Hua, HUANG Xiaomin, ZHANG Chunyan, DU Lu, REN Hong, XU Tian. Value of serum N-terminal pro-brain natriuretic peptide levels in primary screening peritoneal dialysis patients with volume overload[J]. Journal of Internal Medicine Concepts & Practice, 2023, 18(03): 157-164.

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参考文献 28

[4]	Mair J. Biochemistry of B-type natriuretic peptide—where are we now?[J]. Clin Chem Lab Med, 2008, 46(11): 1507-1514.
[5]	Breidthardt T, Kalbermatter S, Socrates T, et al. Increasing B-type natriuretic peptide levels predict mortality in unselected haemodialysis patients[J]. Eur J Heart Fail, 2011, 13: 860-867. doi: 10.1093/eurjhf/hfr057 pmid: 21628312
[6]	Winkler K, Wanner C, Drechsler C, et al. Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death, stroke, myocardial infarction, and all-cause mortality in diabetic dialysis patients[J]. Eur Heart J, 2008, 29: 2092-2099. doi: 10.1093/eurheartj/ehn278 pmid: 18617483
[7]	Gutiérrez OM, Tamez H, Bhan I, et al. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in hemodialysis patients: prognostic value of baseline and follow-up measurements[J]. Clin Chem, 2008, 54(8): 1339-1348. doi: 10.1373/clinchem.2007.101691 pmid: 18539645
[8]	Paniagua R, Amato D, Mujais S, et al. Predictive value of brain natriuretic peptides in patients on peritoneal dialysis[J]. Clin J Am Soc Nephrol, 2008, 3(2): 407-415. doi: 10.2215/CJN.03820907 URL
[9]	Plum J, Schoenicke G, Kleophas W, et al. Comparison of body fluid distribution between chronic haemodialysis and peritoneal dialysis patients as assessed by biophysical and biochemical methods[J]. Nephrol Dial Transplant, 2001, 16(12):2378-2385. doi: 10.1093/ndt/16.12.2378 URL
[10]	van den Wall Bake AW, Kooman JP, Lange JM, et al. Adequacy of peritoneal dialysis and the importance of preserving residual renal function[J]. Nephrol Dial Transplant, 2006, 21 Suppl 2: ii34-ii37.
[11]	Cheng LT, Chen W, Tang W, et al. Residual renal function and volume control in peritoneal dialysis patients[J]. Nephron Clin Pract, 2006, 104(1): c47-c54. doi: 10.1159/000093670 URL
[12]	Devolder I, Verleysen A, Vijt D, et al. Body composition, hydration, and related parameters in hemodialysis versus peritoneal dialysis patients[J]. Perit Dial Int, 2010, 30(2): 208-214. doi: 10.3747/pdi.2008.00284 URL
[13]	Wizemann V, Wabel P, Chamney P, et al. The mortality risk of overhydration in haemodialysis patients[J]. Nephrol Dial Transplant, 2009, 24(5): 1574-1579. doi: 10.1093/ndt/gfn707 URL
[14]	Passauer J, Petrov H, Schleser A, et al. Evaluation of clinical dry weight assessment in haemodialysis patients using bioimpedance spectroscopy[J]. Nephrol Dial Transplant, 2010, 25(2): 545-551. doi: 10.1093/ndt/gfp517 URL
[15]	Lopot F, Nejedly B, Novotná H, et al. Age-related extracellular to total body water volume ratio (Ecv/TBW)—can it be used for "dry weight" determination in dialysis patients?[J]. Int J Artif Organs, 2002, 25(8): 762-769. pmid: 12296460
[16]	Yilmaz Z, Yildirim Y, Oto F, et al. Evaluation of volume overload by bioelectrical impedance analysis, NT-proBNP and inferior vena cava diameter in patients with stage 3&4 and 5 chronic kidney disease[J]. Ren Fail, 2014, 36(4): 495-501. doi: 10.3109/0886022X.2013.875815 URL
[17]	Park WY, Park S, Kim YW, et al. Clinical efficacy of biomarkers for evaluation of volume status in dialysis patients[J]. Medicine (Baltimore), 2020, 99(31): e21460. doi: 10.1097/MD.0000000000021460 URL
[18]	Vickery S, Price CP, John RI, et al. B-type natriuretic peptide(BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy[J]. Am J Kidney Dis, 2005, 46(4): 610-620. doi: 10.1053/j.ajkd.2005.06.017 pmid: 16183415
[19]	Palmer SC, Yandle TG, Nicholls MG, et al. Regional clearance of amino-terminal pro-brain natriuretic peptide from human plasma[J]. Eur J Heart Fail, 2009, 11(9): 832-839. doi: 10.1093/eurjhf/hfp099 pmid: 19605456
[20]	Jacobs LH, van de Kerkhof JJ, Mingels AM, et al. Inflammation, overhydration and cardiac biomarkers in haemodialysis patients: a longitudinal study[J]. Nephrol Dial Transplant, 2010, 25(1): 243-248. doi: 10.1093/ndt/gfp417 URL
[21]	Booth J, Pinney J, Davenport A. N-terminal proBNP—marker of cardiac dysfunction, fluid overload, or malnutrition in hemodialysis patients?[J]. Clin J Am Soc Nephrol, 2010, 5(6): 1036-1040. doi: 10.2215/CJN.09001209 URL
[22]	Ridao N, Luño J, García de Vinuesa S, et al. Prevalence of hypertension in renal disease[J]. Nephrol Dial Transplant, 2001, 16 Suppl 1: 70-73.
[23]	Alvarez-Lara MA, Martín-Malo A, Espinosa M, et al. Blood pressure and body water distribution in chronic renal failure patients[J]. Nephrol Dial Transplant, 2001, 16 Suppl 1: 94-97.
[24]	Celik G, Kara I, Yilmaz M, et al. The relationship between bioimpedance analysis, haemodynamic parameters of haemodialysis, biochemical parameters and dry weight[J]. J Int Med Res, 2011, 39(6): 2421-2428. pmid: 22289562
[25]	Jang M, Kim WH, Lee JH, et al. Numerical expression of volume status using the bioimpedance ratio in continuous ambulatory peritoneal dialysis patients[J]. Kidney Res Clin Pract, 2017, 36(3): 290-295. doi: 10.23876/j.krcp.2017.36.3.290 pmid: 28904881
[26]	Flythe JE, Chang TI, Gallagher MP, et al. Blood pressure and volume management in dialysis[J]. Kidney Int, 2020, 97(5): 861-876. doi: 10.1016/j.kint.2020.01.046 URL
[27]	DeFilippi C, van Kimmenade RR, Pinto YM. Amino-terminal pro-B-type natriuretic peptide testing in renal disease[J]. Am J Cardiol, 2008, 101(3A): 82-88. doi: 10.1016/j.amjcard.2007.11.029 pmid: 18243865
[1]	Zoccali C, Moissl U, Chazot C, et al. Chronic fluid overload and mortality in ESRD[J]. J Am Soc Nephrol, 2017, 28: 2491-2497. doi: 10.1681/ASN.2016121341 pmid: 28473637
[2]	Wang AY, Brimble KS, Brunier G, et al. ISPD cardiovascular and metabolic guidelines in adult peritoneal dialysis patients part Ⅰ-assessment and management of various cardiovascular risk factors[J]. Perit Dial Int, 2015, 35: 379-387. doi: 10.3747/pdi.2014.00279 URL
[3]	Wizemann V, Wabel P, Chamney P, et al. The mortality risk of overhydration in haemodialysis patients[J]. Nephrol Dial Transplant, 2009, 24(5): 1574-1579. doi: 10.1093/ndt/gfn707 URL
[28]	Zoccali C, Mallamaci F, Benedetto FA, et al. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients[J]. J Am Soc Nephrol, 2001, 12(7): 1508-1515. doi: 10.1681/ASN.V1271508 pmid: 11423580

指标	容量正常组（n=59）	容量超负荷组（n=52）	统计量	P
年龄（岁）	55.99±14.75	53.91±14.57	0.155	>0.05
性别（男/女）	29/31	34/18	2.967	>0.05
BMI（kg/m²）	22.53±2.84	22.39±3.38	2.010	>0.05
收缩压（mmHg）	140.00±20.64	152.50±24.12	0.283	0.004
舒张压（mmHg）	82.75±11.72	86.54±13.46	0.608	>0.05
透析龄（月)	62.3（46.5，81.2）	65.8（42.8，92.5）	3 134.0	>0.05
透析剂量（L/24 h）	7.84±1.80	8.46±1.75	0.391	>0.05
尿量（mL/24 h）	800（220，1 200）	300（0，748)	2 373.5	0.001
超滤量（mL/24 h）	500（225，760）	665（325，975）	2 979.0	>0.05
Kt/V	2.24±0.42	2.04±0.49	2.588	0.024
CCr（L/周）	70.75±25.99	58.72±19.22	7.145	0.007
nPCR	0.94±0.16	0.92±0.21	1.910	>0.05
4hD/PCr（μmol/L）	0.59±0.09	0.65±0.11	4.685	0.003
腹膜转运类型（低/高）	44/15	24/28	9.409	0.002
降压药种类（<3种及≥3种）	46/13	22/29	14.058	0.000
利尿剂种类（有/无）	54/5	32/19	13.283	0.000
CRP（mg/L）	1.55（0.52，4.63）	1.87（0.65，5.81）	3 129.5	>0.05
血红蛋白（g/L）	112.22±16.07	105.25±17.27	0.555	0.030
血钠（mmol/L）	141.28±2.86	140.92±2.75	0.348	>0.05
血糖（mmol/L）	5.25±1.78	4.98±1.13	1.370	>0.05
血清白蛋白（mmol/L）	36.71±4.34	33.81±4.83	0.535	0.001
血钙（mmol/L）	2.34±0.16	2.28±0.17	0.632	>0.05
血磷（mmol/L）	1.69±0.45	1.73±0.53	1.749	>0.05
总胆固醇（mmol/L）	5.09±1.07	4.77±1.29	1.966	>0.05
甘油三酯（mmol/L）	2.02±1.10	1.71±1.12	0.016	>0.05
低密度脂蛋白（mmol/L）	3.11±0.93	2.90±1.04	0.820	>0.05
Iog ₂（NT-proBNP）	10.93±2.22	12.60±1.95	1.171	0.000

指标	容量正常组（n=59）	容量超负荷组（n=52）	统计量	P
IVST（mm）	9.90±1.50	11.04±2.10	1.375	0.002
LVPWT（mm）	9.65±1.57	10.51±2.43	2.408	0.037
LAD（mm）	38.50±5.20	41.12±4.68	0.455	0.009
LVESD（mm）	32.42±5.40	32.57±4.63	0.334	>0.05
LVEDD（mm）	50.39±5.56	51.31±4.98	1.458	>0.05
LVESV（mL）	44.50±20.12	44.33±15.93	0.354	>0.05
LVEDV（mL）	122.56±32.64	128.10±29.53	1.126	>0.05
LVEF（%）	64.65±6.69	65.82±5.03	0.546	>0.05
OH（L）	1.4（0.8，2.3）	3.9（3.2，5.28）	1 847.0	0.000
TBW（L）	34.30±7.03	38.28±9.94	3.437	0.016
ECW（L）	15.65±2.90	18.78±4.83	5.361	0.000
ICW（L）	18.65±4.34	19.50±5.46	1.599	>0.05
OH/TBW	0.46（0.24，0.62）	0.11（0.84，0.14）	1 778.0	0.000
ECW/TBW	0.460±0.027	0.493±0.029	0.347	0.000
ECW/ICW	0.855±0.092	0.978±0.116	2.363	0.000

指标	r	P
收缩压	0.320	0.001
透析龄	0.301	0.001
超滤量	0.435	0.000
透析剂量	0.469	0.000
降压药分组	0.404	0.000
IVST	0.534	0.000
LVPWT	0.543	0.000
LAD	0.547	0.000
LVESD	0.346	0.000
LVEDD	0.357	0.000
OH	0.496	0.000
OH/ECW	0.516	0.000
尿量	-0.589	0.000
总Kt/V	-0.352	0.000
总CCr	-0.538	0.000
nPCR	-0.192	0.043
血红蛋白	-0.382	0.000
血清白蛋白	-0.228	0.016
LVEF	-0.213	0.032

指标	NT-proBNP≥4 896 ng/L（n=48）	NT-proBNP<4 896 ng/L（n=63）	统计量	P
BMI（kg/m²）	22.85±2.91	22.15±3.23	0.227	>0.05
收缩压（mmHg）	152.40±25.06	140.29±19.95	2.032	0.005
尿量（mL/24 h）	135.0（0，437.5）	800（500，1 200）	1 792.5	0.000
超滤量（mL/24 h）	767.0（500.0，1 022.5）	480（224，698）	2 896.0	0.000
Kt/V	1.97±0.38	2.28±0.47	1.033	0.000
CCr（L/周）	51.7（45.8，56.9）	69.3（52.8，90.3）	1 886.0	0.000
IVST（mm）	11.47±2.07	9.71±1.34	2 261.5	0.000
LVPWT（mm）	11.16±2.49	9.26±1.18	2 248	0.000
LVEF（%）	63.84±7.48	66.24±7.48	1 996.5	0.044
OH/ECW	0.21±0.10	0.12±0.07	5.593	0.000