特发性膜性肾病患者血栓栓塞事件发病率及危险因素的队列研究

doi:10.24920/11809

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This large retrospective study investigated the incidence and risk factors for thromboembolic events in IMN patients. The authors found increased incidences for ATE and VTE, especially in 6 month after diagnosis of the disease. Severe proteinuria, hypoalbuminemia, and those risk factors for atherosclerosis were found to be associated with thromboembolic events.

Abstract

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ ²=18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

Key words: idiopathic membranous nephropathy, thromboembolic events, arterial, venous

Zou Peimei, Li Hang, Cai Jianfang, Chen Zhenjie, Li Chao, Xu Ping, Li Mingxi, Chen Limeng, Li Xuemei, Li Xuewang. A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy[J].Chinese Medical Sciences Journal, 2018, 33(2): 91-99.

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References 23.

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	ATEs (n=71)	VTEs (n=53)	Pvalue
Sex, n (%)			0.84
Male	44(62.0)	34(64.2)
Female	27(38.0)	19(35.8)
Age, year	57.0±11.9	49.6±14.8	0.003
History of
Smoking, n(%)	31 (43.7)	15 (28.3)	0.08
Hypertension, n (%)	46 (64.8)	26 (49.1)	0.08
Diabetes, n(%)	16 (22.5)	14 (26.4)	0.62
Prior ATE, n(%)	4 (5.6)	2 (3.8)	0.63
Observation time, month	43.2 (5.4, 145.1)	43.6 (21.5, 62.0)	0.41
Proteinuria, g/24 h	6.38 (3.79, 10.16)	7.30 (4.88, 10.54)	0.15
Serum albumin, g/L	26.7±6.3	25.8±6.6	0.45
eGFR, ml/min/1.73 m²	88.65±22.27	97.22±18.86	0.03
Total cholesterol, mmol/L	7.98±2.42	8.87±2.84	0.11
Triglycerides, mmol/L	2.43 (1.81, 3.60)	3.32 (1.96, 4.71)	0.10
LDL-C, mmol/L	5.41±2.19	5.63±2.48	0.68
NS, n (%)	49 (69.0)	38 (71.7)	0.75

Characteristics	ATEs (n=58)				VTEs (n=56)				P value^?
Characteristics	Mean/ Median	Early onset (n=27)	Delayed onset (n=31)	P value*	Mean/ Median	Early onset (n=48)	Delayed onset (n=8)	P value*	P value^?
Age, year	59.0±11.4	59.4±11.8	58.7±11.2	0.81	50.0±15.4	49.0±16.0	56.4±9.5	0.21	0.001
Proteinuria, g/24 h	3.5(1.05, 7.12)	4.5(2.0, 6.7)	2.8(0.7, 7.8)	0.33	6.2(4.5, 9.6)	6.2(4.5, 9.8)	6.7(4.4, 9.2)	0.76	0.002
Serum albumin, g/L	29.8±8.0	26.8±7.6	32.4±7.5	0.01	25.1±7.7	25.1±8.1	25.1±5.8	1.00	0.002
eGFR, ml/min/ 1.73m²	84.2±22.1	87.5±20.8	81.6±23.1	0.35	94.8±22.3	96.6±21.4	84.0±26.3	0.14	0.02
Total cholesterol, mmol/L	7.4(5.1, 8.9)	7.8(6.5, 8.9)	6.1(4.9, 9.3)	0.11	8.0(6.3, 9.3)	8.4±2.7	7.9±1.4	0.66	0.21
Triglycerides, mmol/L	2.1(1.7, 3.0)	2.1(1.7, 4.3)	2.6(1.1, 2.9)	0.75	3.4(1.9, 4.4)	3.4(2.0, 4.0)	1.9(1.6, 4.8)	0.63	0.04
LDL-C, mmol/L	4.3(2.7, 6.5)	5.5(2.7, 6.7)	3.8(2.6, 6.4)	0.27	4.5(3.4, 7.0)	4.5(3.3, 7.2)	4.51(3.45, -)	0.87	0.54
NS, n (%)									< 0.001
NS status	24 (42.1)	16 (59.3)	8 (26.7)	0.01	44 (81.5)	38 (79.2)	6 (75.0)	N/A
Sub-NS	22 (38.6)	10 (37.0)	12 (38.7)		8 (14.8)	8 (16.7)	0 (0.0)
CR	11 (19.3)	1 (3.7)	10 (35.5)		2 (3.7)	2 (4.2)	0 (0.0)

Variables	n	ATE			VTE
Variables	n	HR	95% CI	Pvalue	HR	95% CI	P value
Sex, male	449	1.2	0.8-2.0	0.39	1.6	0.8-2.4	0.29
Age, years	766			< 0.001			0.35
<35	167	1.0	reference		1.0	reference
35-54	323	5.1	1.2-21.7		0.8	0.4-1.7
≥55	276	13.0	3.1-53.3		1.3	0.6-2.6
History of	766
Smoking	228	1.7	1.0-2.7	0.03	0.9	0.5-1.7	0.81
Hypertension	360	1.8	1.1-3.0	0.02	0.9	0.5-1.6	0.77
Diabetes	90	1.5	0.8-2.8	0.24	1.3	0.6-2.9	0.44
ATE	35	2.4	1.1-5.2	0.03	0.8	0.2-3.4	0.79
Proteinuria, g/24 h	712			0.04			0.03
<3.5	191	1.0	reference		1.0	reference
3.5-8.0	313	1.3	0.7-2.7		3.6	1.3-10.5
>8.0	208	2.2	1.1-4.4		4.3	1.5-12.8
Serum albumin, g/L	710			0.64			0.01
<20	73	1.6	0.6-4.4		5.5	1.5-19.9
20-35	198	1.4	0.6-3.0		2.3	0.7-7.6
≥35	246	1.0	reference		1.0	reference
eGFR, ml/min/1.73 m²	760			0.10			0.27
≥90	517	1.0	reference		1.0	reference
60-89	195	1.4	0.8-2.4		1.4	0.8-2.5
<60	48	2.2	1.0-4.8		0.3	0.1-2.4
Total cholesterol, mmol/L	543			0.97			0.14
<5.18	43	1.0	reference		1.0	reference
5.18-7.76	240	0.9	0.3-2.4		2.4	0.3-18.3
>7.76	260	0.9	0.3-2.3		4.1	0.6-30.5

ATE				VTE
Variables	HR	95% CI	Pvalue	Variables	HR	95% CI	Pvalue
History of				Serum albumin, g/L			0.03
Smoker	1.4	0.8-2.4	0.19	<20	3.2	0.8-12.5
ATE	1.6	0.7-3.5	0.28	20-35	1.3	0.4-4.5
Hypertension	1.1	0.6-1.8	0.84	≥35	1.0	reference
Age, years			0.001
<35	1.0	reference
35-54	4.4	1.0-19.1
≥55	9.2	2.2-39.5
Proteinuria, g/24 h			0.11	Proteinuria, g/24 h			0.13
<3.5	1.0	reference		<3.5	1.0	reference
3.5-8.0	1.1	0.6-2.3		3.5-8.0	3.0	1.0-8.9
>8.0	1.9	0.9-3.8		>8.0	3.2	1.0-10.1

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A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy

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