纤维蛋白原/白蛋白比值与系统性红斑狼疮肾脏损害及疾病活动度的相关性

张想想; 潘海峰; 王德光

doi:10.16462/j.cnki.zhjbkz.2023.08.011

纤维蛋白原/白蛋白比值与系统性红斑狼疮肾脏损害及疾病活动度的相关性

doi: 10.16462/j.cnki.zhjbkz.2023.08.011

1.
安徽医科大学第二附属医院肾脏内科，合肥 230601
2.
安徽医科大学公共卫生学院流行病与卫生统计学系，合肥 230032

基金项目:

安徽省自然科学基金 2008085MH244

安徽医科大学第二附属医院国家自然科学基金孵育计划项目 2020GMFY04

安徽医科大学2020年临床与前期学科共建项目 2020lcxk022

详细信息

通讯作者:
王德光，E-mail：wangdeguang@ahmu.edu.cn

中图分类号: R593.241
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出版历程
- 收稿日期: 2022-06-07
- 修回日期: 2022-09-25
- 网络出版日期: 2023-09-02
- 刊出日期: 2023-08-10

The correlation analysis between the fibrinogen-albumin ratio and renal damage and disease activity of systemic lupus erythematosus

1.
Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
2.
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei 230032, China

Funds:

Natural Science Foundation of Anhui Province 2008085MH244

Incubation Program of National Natural Science Foundation of China of The Second Hospital of Anhui Medical University 2020GMFY04

Co-construction Project of Clinical and Preliminary Disciplines of Anhui Medical University in 2020 2020lcxk022

More Information

Corresponding author: WANG Deguang, E-mail: wangdeguang@ahmu.edu.cn

摘要

摘要: 目的探讨系统性红斑狼疮(systemic lupus erythematosus, SLE)初诊患者纤维蛋白原/白蛋白比值(fibrinogen-albumin ratio, FAR)与肾脏损害及疾病活动度的相关性。方法以159例健康人群作为对照组，回顾性分析156例SLE初诊患者的相关临床数据。结果 SLE患者的FAR明显高于对照组(Z=-10.390, P < 0.001)，SLE患者中重度活动组FAR明显高于轻度活动组(Z=-4.703, P < 0.001)，狼疮肾炎组FAR明显高于非狼疮肾炎组(Z=-6.312, P < 0.001)；SLE患者的FAR和补体C3(r=-0.249, P=0.002)、血清总蛋白(r=-0.474, P < 0.001)呈负相关，和血沉(r=0.383, P < 0.001)、C-反应蛋白(r=0.293, P < 0.001)、血尿素氮(r=0.220, P=0.006)、血尿酸(r=0.296, P < 0.001)、血肌酐(r=0.180, P=0.025)、24 h尿蛋白(r=0.588, P < 0.001)及SLE疾病活动度指数(r=0.430, P < 0.001)呈正相关；多因素logistic回归分析模型分析显示FAR是SLE疾病中重度活动(OR=1.010, 95% CI: 1.003~1.018, P=0.008)、肾脏损害(OR=1.020, 95% CI: 1.009~1.032, P < 0.001)的独立危险因素。根据受试者工作特征曲线，FAR用于诊断SLE、SLE疾病中重度活动及肾脏损害的曲线下面积分别为0.84(95% CI: 0.79~0.88)、0.72(95% CI: 0.64~0.80)及0.80(95% CI: 0.72~0.87)。结论 FAR与SLE患者疾病活动度、肾脏损害相关，对评估SLE疾病活动度及肾脏损害具有一定的临床意义。
- 纤维蛋白原/白蛋白比值 /
- 系统性红斑狼疮 /
- 狼疮肾炎 /
- 疾病活动度
Abstract: Objective To explore the relationship between the fibrinogen-albumin ratio (FAR) and renal damage and disease activity in newly diagnosed patients with systemic lupus erythematosus (SLE). Methods The medical records of relevant clinical data of 156 newly diagnosed SLE patients and 159 healthy controls were retrospectively analyzed. Results The FAR of SLE patients was significantly higher than that of healthy controls (Z=-10.390, P < 0.001). The FAR of SLE patients in the moderate and severe disease activity group was higher than that in the mild disease activity group (Z=-4.703, P < 0.001). The FAR in lupus nephritis group was significantly higher than that in non-lupus nephritis group (Z=-6.312, P < 0.001). The FAR of SLE patients was negatively correlated with complement 3 (r=-0.249, P=0.002), serum total protein (r=-0.474, P < 0.001), and positively correlated with erythrocyte sedimentation rete (r=0.383, P < 0.001), C-reactive protein (r=0.293, P < 0.001), blood urea nitrogen (r=0.220, P=0.006), uric acid (r=0.296, P < 0.001), creatinine (r=0.180, P=0.025), 24-hour urine protein (r=0.588, P < 0.001) and SLE disease activity index (r=0.430, P < 0.001). Multivariate logistic regression analysis showed that FAR was an independent risk factor for moderate to severe SLE activity and renal damage. According to receiver operating characteristic curve, the areas under the curve of FAR for diagnosis of SLE, prediction of moderate to severe SLE activity and renal damage were 0.84(95% CI: 0.79-0.88), 0.72(95% CI: 0.64-0.80), 0.80(95% CI: 0.72-0.87), respectively. Conclusions FAR is associated with disease activity and renal damage in SLE patients, and has certain clinical significance for assessing SLE disease activity and renal damage.
- Fibrinogen-albumin ratio /
- Systemic lupus erythematosus /
- Lupus nephritis /
- Disease activity

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图 1 FAR诊断SLE、SLE疾病中重度活动及肾脏损害的ROC曲线

1. A: FAR诊断SLE的ROC曲线；2. B : FAR诊断SLE疾病中重度活动的ROC曲线；3. C : FAR诊断SLE肾脏损害的ROC曲线；4. AUC：曲线下面积；5. FAR: 纤维蛋白原/白蛋白比值；6. SLE: 系统性红斑狼疮；7. ROC: 受试者工作特征。

Figure 1. ROC curve of FAR for the diagnosis of SLE, moderate to severe SLE activity and renal damage

1. A: ROC curve for FAR diagnosis of SLE; 2. B: ROC curve for the diagnosis of moderate to severe SLE disease by FAR; 3. C: ROC curve for FAR to diagnose renal impairment in SLE; 4.AUC: areas under curve; 5. FAR: fibrinogen-albumin ratio; 6. SLE: systemic lupus erythematosus; 7. ROC: receiver operating characteristic.

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表 1 SLE组和对照组的一般资料及实验室指标比较

Table 1. Comparison of general data and laboratory indicators between SLE patients and controls

参数Parameter	对照组 Control group (n=159)	SLE组 SLE group (n=156)	t/z/χ²值 value	P值 value
年龄/岁, (x±s) Age/years, (x±s)	37.35±12.26	36.01±13.76	0.917	0.360
性别(男/女) Gender (male/female)	21/138	16/140	0.662	0.416
WBC/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	5.85(4.93, 6.92)	3.31(2.58, 4.48)	-11.305	< 0.001
N/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	3.28(2.68, 4.02)	2.01(1.57, 2.96)	-8.288	< 0.001
L/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	1.81(1.50, 2.32)	0.84(0.63, 1.13)	-13.286	< 0.001
M/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	0.40(0.32, 0.50)	0.29(0.22, 0.38)	-6.210	< 0.001
RBC/(×10¹²·L^-1), [M(P₂₅, P₇₅)]	4.33(4.05, 4.62)	3.72(3.23, 4.02)	-10.284	< 0.001
Hb/(g·L^-1), [M(P₂₅, P₇₅)]	127.00(120.00, 135.00)	105.00(90.25, 116.00)	-10.462	< 0.001
PLT/(×10⁹·L^-1), (x±s)	223.74±51.22	138.37±75.39	11.735	< 0.001
STP/(g·L^-1), [M(P₂₅, P₇₅)]	67.50(63.50, 71.50)	69.55(60.50, 74.60)	-0.398	0.691
Alb/(g·L^-1), [M(P₂₅, P₇₅)]	41.00(39.00, 43.10)	32.05(25.35, 36.53)	-12.908	< 0.001
G/(g·L^-1), [M(P₂₅, P₇₅)]	26.50(23.80, 29.60)	36.80(31.23, 41.80)	-10.960	< 0.001
BUN/(mmol·L^-1), [M(P₂₅, P₇₅)]	4.84(4.00, 5.72)	4.30(3.23, 5.80)	-1.756	0.079
UA/(μmol·L^-1), [M(P₂₅, P₇₅)]	278.00(235.00, 336.00)	283.00(225.25, 365.75)	-0.015	0.988
Cr/(μmol·L^-1), [M(P₂₅, P₇₅)]	53.00(47.00, 64.00)	61.00(48.25, 74.00)	-3.385	0.001
Fib/(μmol·L^-1), [M(P₂₅, P₇₅)]	2 440.00(2 120.00, 2 780.00)	2 925.00(2 382.50, 3 680.00)	-6.025	< 0.001
FAR[M(P₂₅, P₇₅)]	60.34(50.48, 67.03)	90.43(68.16, 136.04)	-10.390	< 0.001
注：WBC, 白细胞数；N, 中性粒细胞数；L, 淋巴细胞数；M, 单核细胞数；RBC, 红细胞数；Hb, 血红蛋白；PLT, 血小板数；STP, 血清总蛋白；Alb, 白蛋白；G, 球蛋白；BUN, 尿素氮；UA, 尿酸；Cr, 肌酐；Fib, 纤维蛋白原；FAR, 纤维蛋白原/白蛋白比值; SLE, 系统性红斑狼疮。 Note：WBC, white blood cell count; N, neutrophil count; L, lymphocyte count; M, monocyte count; RBC, red blood cell count; Hb, hemoglobin; PLT, platelet count; STP, serum total protein; Alb, albumin; G, globulin; BUN, blood urea nitrogen; UA, uric acid; Cr, creatinine; Fib, fibrinogen; FAR, fibrinogen-albumin ratio; SLE, systemic lupus erythematosus.

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表 2 不同分组的SLE患者的一般资料及实验室指标比较

Table 2. Comparison of general data and laboratory indicators of SLE patients in different groups

参数Parameter	根据疾病活动度分组Patients were grouped according to disease activity
参数Parameter	轻度活动组 Mild activity group (n=74)	中重度活动组 Moderate to severe activity group (n=82)	t/z/Ω²值 value	P值 value
年龄/岁, (x±s) Age/years, (x±s)	36.01±12.77	36.00±14.68	0.006	0.995
性别(男/女) Gender (male/female)	6/68	10/72	0.706	0.401
WBC/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	3.27(2.55, 4.31)	3.38(2.63, 4.80)	-0.524	0.601
N/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	1.88(1.47, 2.74)	2.05(1.61, 3.08)	-1.248	0.212
L/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	0.89(0.67, 1.16)	0.81(0.56, 1.11)	-1.081	0.280
M/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	0.30(0.23, 0.38)	0.28(0.21, 0.38)	-0.879	0.380
RBC/(×10¹²·L^-1), [M(P₂₅, P₇₅)]	3.84(3.33, 4.05)	3.70(3.13, 4.01)	-1.154	0.249
Hb/(g·L^-1), (x±s)或[M(P₂₅, P₇₅)]	105.61±21.88	100.12±20.02	1.635	0.104
PLT/(×10⁹·L^-1), (x±s)	135.37±78.96	141.07±72.39	-0.471	0.639
STP/(g·L^-1), [M(P₂₅, P₇₅)]	71.60(66.55, 77.03)	62.85(55.95, 73.95)	-4.383	< 0.001
Alb/(g·L^-1), (x±s)	34.17±6.03	27.54±7.44	6.132	< 0.001
G/(g·L^-1), (x±s)或[M(P₂₅, P₇₅)]	36.95(32.30, 42.10)	36.45(29.30, 40.65)	-1.182	0.237
BUN/(mmol·L^-1), [M(P₂₅, P₇₅)]	4.21(3.07, 5.40)	4.44(3.44, 6.82)	-1.941	0.052
UA/(μmol·L^-1), [M(P₂₅, P₇₅)]	249.50(203.30, 321.25)	329.50(236.50, 410.00)	-3.668	< 0.001
Cr/(μmol·L^-1), [M(P₂₅, P₇₅)]	55.50(47.00, 67.25)	65.00(52.75, 82.50)	-2.741	0.006
Fib/(μmol·L^-1), [M(P₂₅, P₇₅)]	2 625.00(2 207.50, 3 435.00)	3 220.00(2 520.00, 3 732.50)	-2.543	0.011
24 h尿蛋白/(mg·d^-1), [M(P₂₅, P₇₅)] 24 hour urine protein /(mg·d^-1), [M(P₂₅, P₇₅)]	164.15(97.56, 324.56)	1 311.70(424.43, 3 966.33)	-6.894	< 0.001
CRP/(mg·L^-1), [M(P₂₅, P₇₅)]	3.62(1.00, 7.83)	4.80(1.55, 7.40)	-0.709	0.479
ESR/(mm·h^-1), [M(P₂₅, P₇₅)]	21.00(11.00, 42.25)	25.00(12.00, 40.25)	-0.366	0.715
C3/(g·L^-1), [M(P₂₅, P₇₅)]	0.62(0.44, 0.84)	0.40(0.28, 0.61)	-4.551	< 0.001
C4/(g·L^-1), [M(P₂₅, P₇₅)]	0.10(0.05, 0.15)	0.05(0.04, 0.10)	-2.509	0.012
抗ds-DNA抗体阳性率/% Positive rate of anti-ds-DNA antibody /%	21.60	37.80	4.839	0.028
抗Sm抗体阳性率/% Positive rate of anti-Sm antibody /%	36.50	34.10	0.093	0.760
抗SSA抗体阳性率/% Positive rate of anti-SSA antibody /%	56.80	65.90	1.360	0.244
抗SSB抗体阳性率/% Positive rate of anti-SSB antibody /%	5.40	18.30	6.040	0.014
SLEDAI[M(P₂₅, P₇₅)]
FAR[M(P₂₅, P₇₅)]	74.90(62.65, 110.13)	111.32(82.12, 154.08)	-4.703	< 0.001

参数Parameter	根据有无肾脏损害分组Patients were grouped according to the presence or absence of renal damage
参数Parameter	SLE-NLN组 SLE without LN group (n=88)	SLE-LN组 SLE with LN group (n=68)	t/z/χ²值 value	P值 value
年龄/岁, (x±s) Age/years, (x±s)	35.86±13.76	36.19±13.88	-0.147	0.884
性别(男/女) Gender (male/female)	4/84	12/56	7.153	0.007
WBC/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	3.22(2.57, 4.04)	3.40(2.62, 4.87)	-0.820	0.412
N/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	1.91(1.51, 2.67)	2.05(1.58, 3.35)	-0.906	0.365
L/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	0.87(0.66, 1.15)	0.82(0.59, 1.10)	-0.556	0.578
M/(×10⁹·L^-1), [M(P₂₅, P₇₅)]	0.29(0.21, 0.36)	0.30(0.23, 0.43)	-0.953	0.341
RBC/(×10¹²·L^-1), [M(P₂₅, P₇₅)]	3.82(3.38, 4.08)	3.69(3.00, 3.96)	-1.596	0.111
Hb/(g·L^-1), (x±s)或[M(P₂₅, P₇₅)]	108.50(92.25, 118.00)	102.50(87.00, 114.00)	-1.823	0.068
PLT/(×10⁹·L^-1), (x±s)	135.83±81.62	141.65±66.91	-0.476	0.634
STP/(g·L^-1), [M(P₂₅, P₇₅)]	72.00(66.88, 76.80)	61.35(54.55, 69.73)	-6.115	< 0.001
Alb/(g·L^-1), (x±s)	34.54±5.45	25.70±6.99	8.603	< 0.001
G/(g·L^-1), (x±s)或[M(P₂₅, P₇₅)]	37.60±8.30	35.29±8.47	1.708	0.090
BUN/(mmol·L^-1), [M(P₂₅, P₇₅)]	4.20(3.11, 5.34)	5.05(3.47, 7.58)	-2.718	0.007
UA/(μmol·L^-1), [M(P₂₅, P₇₅)]	249.50(194.25, 305.00)	349.00(260.50, 422.50)	-4.911	< 0.001
Cr/(μmol·L^-1), [M(P₂₅, P₇₅)]	56.50(48.00, 67.00)	66.00(53.25, 87.75)	-2.881	0.004
Fib/(μmol·L^-1), [M(P₂₅, P₇₅)]	2 645.00(2 232.50, 3 332.50)	3 380.00(2 705.00, 4 027.50)	-4.012	< 0.001
24 h尿蛋白/(mg·d^-1), [M(P₂₅, P₇₅)] 24 hour urine protein /(mg·d^-1), [M(P₂₅, P₇₅)]	139.23(89.01, 233.00)	2 155.35(1 147.58, 5 408.13)	-10.693	< 0.001
CRP/(mg·L^-1), [M(P₂₅, P₇₅)]	3.62(1.10, 7.70)	4.99(1.60, 7.31)	-0.960	0.337
ESR/(mm·h^-1), [M(P₂₅, P₇₅)]	20.50(10.00, 40.00)	26.50(15.00, 43.00)	-1.816	0.069
C3/(g·L^-1), [M(P₂₅, P₇₅)]	0.58(0.43, 0.82)	0.39(0.28, 0.53)	-4.300	< 0.001
C4/(g·L^-1), [M(P₂₅, P₇₅)]	0.09(0.05, 0.14)	0.05(0.03, 0.10)	-2.169	0.030
参数Parameter	根据有无肾脏损害分组Patients were grouped according to the presence or absence of renal damage
参数Parameter	SLE-NLN组 SLE without LN group (n=74)	SLE-LN组 SLE with LN group (n=82)	t/z/χ²值 value	P值 value
抗ds-DNA抗体阳性率/% Positive rate of anti-ds-DNA antibody /%	28.40	32.40	0.283	0.594
抗Sm抗体阳性率/% Positive rate of anti-Sm antibody /%	34.10	36.80	0.120	0.729
抗SSA抗体阳性率/% Positive rate of anti-SSA antibody /%	58.00	66.20	1.096	0.295
抗SSB抗体阳性率/% Positive rate of anti-SSB antibody /%	8.00	17.60	3.369	0.066
SLEDAI[M(P₂₅, P₇₅)]	7.00(5.00, 10.00)	14.00(11.00, 20.00)	-7.719	< 0.001
FAR[M(P₂₅, P₇₅)]	75.45(63.26, 103.07)	132.31(88.69, 177.81)	-6.312	< 0.001
注：WBC, 白细胞数；N, 中性粒细胞数；L, 淋巴细胞数；M, 单核细胞数；RBC, 红细胞数；Hb, 血红蛋白；PLT, 血小板数；STP, 血清总蛋白；Alb, 白蛋白；G, 球蛋白；BUN, 尿素氮；UA, 尿酸；Cr, 肌酐；Fib, 纤维蛋白原；CRP, C-反应蛋白；ESR, 红细胞沉降率；C3, 补体3；C4, 补体4；ds-DNA, 双链DNA；Sm, 人名，Smith；SSA, 干燥综合征抗原A；SSB, 干燥综合征抗原B；SLEDAI, 系统性红斑狼疮疾病活动度指数；FAR, 纤维蛋白原/白蛋白比值；SLE, 系统性红斑狼疮；SLE-NLN, 系统性红斑狼疮非合并狼疮肾炎；SLE-LN, 系统性红斑狼疮合并狼疮肾炎。 Note：WBC, white blood cell count; N, neutrophil count; L, lymphocyte count; M, monocyte count; RBC, red blood cell count; Hb, hemoglobin; PLT, platelet count; STP, serum total protein; Alb, albumin; G, gobulin; BUN, blood urea nitrogen; UA, uric acid; Cr, creatinine; Fib, fibrinogen; CRP, c-reactive protein; ESR, erythrocyte sedimentation rete; C3, complement 3; C4, complement 4; ds-DNA, double stranded DNA; Sm, name，smith; SSA, sjogren′s syndrome antigen A; SSB, sjogren′s syndrome antigen B; SLEDAI, systemic lupus erythematosus disease activity index; FAR, fibrinogen-albumin ratio; SLE, systemic lupus erythematosus; SLE-NLN, systemic lupus erythematosus without lupus nephritis; SLE-LN, systemic lupus erythematosus with lupus nephritis.

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表 3 SLE疾病中重度活动、肾脏损害的多因素logistic回归分析

Table 3. Multivariate logistic regression analysis of moderate to severe SLE activity and renal damage

变量Variable	SLE疾病中重度活动Moderate to severe SLE activity					变量Variable	SLE肾脏损害Renal damage in SLE
变量Variable	β值 value	SE	Wald值 value	OR值(95% CI) OR value (95% CI)	P值 value	变量Variable	β值 value	SE	Wald值 value	OR值(95% CI) OR value (95% CI)	P值 value
FAR	0.010	0.004	7.090	1.010(1.003~1.018)	0.008	性别=男性 (Gender=male)	0.928	0.895	1.075	2.529(0.438~14.607)	0.300
C3/(g·L^-1)	-1.978	0.946	4.372	0.138(0.022~0.883)	0.037	FAR	0.020	0.006	12.508	1.020(1.009~1.032)	< 0.001
C4/(g·L^-1)	1.765	3.340	0.279	5.842(0.008~4 073.158)	0.597	SLEDAI	0.280	0.061	21.113	1.323(1.174~1.490)	< 0.001
Cr/(μmol·L^-1)	0.002	0.008	0.087	1.002(0.986~1.019)	0.767	C3(/g·L^-1)	-1.635	1.244	1.728	0.195(0.017~2.231)	0.189
UA/(μmol·L^-1)	0.004	0.002	3.661	1.004(1.000~1.008)	0.056	C4/(g·L^-1)	4.130	4.210	0.962	62.183(0.016~238 282.084)	0.327
抗ds-DNA抗体+ Anti-ds-DNA antibody/+	0.734	0.418	3.091	2.084(0.919~4.724)	0.079	BUN/(mmol·L^-1)	0.128	0.158	0.655	1.136(0.834~1.549)	0.418
抗SSB抗体+ Anti-SSB antibody/+	1.422	0.658	4.672	4.145(1.142~15.050)	0.031	Cr/(μmol·L^-1)	-0.018	0.014	1.644	0.983(0.957~1.009)	0.200
						UA/(μmol·L^-1)	0.005	0.002	3.946	1.005(1.000~1.010)	0.047
注：FAR, 纤维蛋白原/白蛋白比值; C3, 补体3; C4, 补体4; Cr, 肌酐; UA, 尿酸; ds-DNA, 双链DNA; SSB, 干燥综合征抗原B; SLEDAI, 系统性红斑狼疮疾病活动度指数; BUN, 尿素氮。 Note：FAR, fibrinogen-albumin ratio; C3, complement 3; C4, complement 4; Cr, creatinine; UA, uric acid; ds-DNA, double stranded DNA; SSB, sjogren′s syndrome antigen B; SLEDAI, systemic lupus erythematosus disease activity index; BUN, blood urea nitrogen.

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