
==== Front
BMC Nephrol
BMC Nephrol
BMC Nephrology
1471-2369
BioMed Central London

3704
10.1186/s12882-024-03704-w
Research
The risk of thromboembolic events in patients with nephrotic syndrome and relatively high albumin levels: a study over 10 years
Liu Yi-meng 123
Gao Shuang 123
Liu Li-jun lijun.liu@aliyun.com

123
1 grid.11135.37 0000 0001 2256 9319 Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
2 https://ror.org/03m01yf64 grid.454828.7 0000 0004 0638 8050 Key Laboratory of Renal Disease, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Ministry of Health of China, Beijing, China
3 https://ror.org/02drdmm93 grid.506261.6 0000 0001 0706 7839 Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
11 9 2024
11 9 2024
2024
25 30118 10 2023
8 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients.

Methods

This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software.

Results

There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01).

Conclusions

Our study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events.

Keywords

Albumin
Nephrotic syndrome
Thromboembolic events
Venous thrombus embolism
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pmcIntroduction

Thromboembolic events are common complications of NS (nephrotic syndrome). Within the first 6 months of NS, the risks of thromboembolic events, both VTE (venous thrombus embolism) and ATE (atrial thrombus embolism), are considered to be particularly high (annual incidences, 9.85% and 5.52%) [1]. Regardless of the primary factors of the disease or the secondary factors caused by subsequent treatment, various factors jointly participate in the hypercoagulable state of patients with NS and lead to thromboembolic events, further worsening their prognosis.

In the 2021 KDIGO clinical practice guideline, histological diagnosis [especially of MN (membranous nephropathy), proteinuria level (24-h proteinuria > 10 g/d), and serum albumin level (< 25 g/L) are listed as the best predictors of VTE for glomerulonephritis. Regardless of the degree of proteinuria, a low serum albumin level is considered to increase the VTE risk independently [2]. The VTE risk increases proportionately with declining albumin level. A large cohort study identified a total of 158 VTE events in 7037 patients [absolute event rate (AER) 2.25%], an AER of 4.1% in patients with albumin < 2.5 g/dL, an AER of 3.4% in patients with albumin 2.5–2.99 g/dL, an AER of 2.5% in patients with albumin 3–3.99 g/dL and an AER of only 1.4% in patients with albumin > 4 g/dL [3]. On the other hand, ATE has been associated with eGFR (estimated glomerular filtration rate) and multiple classical risk factors for atherosclerosis but not with either proteinuria or serum albumin level in patients with NS [1].

While current prophylactic anticoagulation indications mainly focus on low serum albumin level (< 25 g/L), little is known about the proportion and characteristics of patients with relatively high serum albumin levels. Therefore, we conducted a study to explore the proportion of patients with relatively high albumin levels among those with NS and relevant thromboembolic events and to assess the difference between those with relatively high albumin levels (≥ 25 g/L) and low albumin levels (< 25 g/L). Our findings could help with clinical decision making in regard to prophylactic anticoagulation.

Materials and Methods

Study patients

This study recruited all hospitalized patients in Peking University First Hospital for the past 10 years (2012–2022) who had diagnoses of NS and relevant thromboembolic events.

The diagnosis of NS was recorded if a patient had proteinuria greater than 3.5 g/day with a serum albumin level less than 30 g/L or a previous diagnosis of NS before hospital admission [2]. The diagnoses of thromboembolic events varied between thrombus types: DVT (deep venous thrombosis) was confirmed by ultrasonography (mainly by leg vein Doppler), PE (pulmonary embolism) was confirmed by computer tomography pulmonary angiography (CTPA) or perfusion lung scanning, RVT (renal venous thrombosis) was confirmed by renal ultrasonography, and ATE was confirmed by computed tomography scanning or magnetic resonance imaging. The main exclusion criteria were patients whose thromboembolic events were clinically decided to be caused by other diseases and patients whose serum albumin levels were not available within a week of the diagnoses of their thromboembolic events.

Data collection

Multiple characteristics, including demographic characteristics, laboratory examinations, pathological classifications, prior treatment during the whole course,combination with autoimmune disease, other factors related to thromboembolism and time of the occurrence of thromboembolic events were collected. For demographic characteristics, age, sex, smoking, and body mass index (BMI) were collected. The laboratory examinations were red blood cells (RBCs), hemoglobin, platelet, albumin, eGFR, 24-h proteinuria, lipids and coagulation parameters. The data were collected from the latest laboratory examinations before the thromboembolic events were confirmed. In particular, coagulation parameters, including D-dimer, FDP (fibrinogen degradation product), FIB (fibrinogen), protein C, protein S, and antithrombin, were recorded. Former usage of steroids, immunosuppressants, diuretics, albumin infusions, and anticoagulants were recorded as prior treatment. Confirmed autoimmune disease, lupus anticoagulant and anti-phospholipid antibodies were recorded in autoimmune disease. The severity of edema, former hospitalization/longtime bedrest, confirmed/suspected neoplasms were recorded as other factors related to thromboembolism.

Moreover, pathological classification was recorded if renal biopsy was performed. All biopsies were examined by light microscopy and immunofluorescence electron microscopy. In particular, the serum level of anti-PLA2R antibody was measured by ELISA and was considered positive at > 20 U/ml [4]. If the anti-PLA2R antibody was positive in a patient without renal biopsy, the disease was classified as MN because the specificity of a positive anti-PLA2R antibody test for the diagnosis of MN is 0.99 [2].

Statistical analysis

For categorical data, the results were expressed as percentages and were compared between groups by the chi-square test (serum albumin levels < 25 vs. ≥ 25 g/L). For continuous data that were normally distributed, the results were expressed as mean ± standard deviation (SD) and were compared by the independent-samples t test. For continuous data that were nonnormally distributed, the results were expressed as median [interquartile range (IQR)] and were compared by the Mann–Whitney test. P values were considered statistically significant if they were less than 0.05. The data were analyzed using Statistical Product and Service Solutions (SPSS) 20.0 (IBM, New York, USA).

Results

Clinical characteristics

There were 312 hospitalized patients with NS in our center over the past 10 years (2012–2022) who had NS-associated thromboembolic events, 84 (26.9%) with serum albumin levels ≥ 25 g/L (relatively high-albumin group) and 228 (73.1%) with serum albumin levels < 25 g/L (relatively low-albumin group). Table 1 lists the baseline characteristics of the two groups. Table 1 Characteristics of patients with NS and relevant thromboembolic events

Characteristics	Albumin ≥ 25 g/L (n = 84)	Albumin < 25 g/L (n = 228)	P value	
Demographic characteristics	
 Gender, Male (n, %)	57 (67.9%)	170 (74.6%)	0.26	
 Smoking (n, %)	25 (29.8%)	92 (40.4%)	0.08	
 Age (in years)	51.0 ± 17.2	52.6 ± 17.2	0.46	
 BMI (kg/m2)	25.8 ± 3.8	25.7 ± 3.8	0.82	
Laboratory examinations	
 RBC (*1012/L)	4.2 ± 0.9	4.0 ± 0.9	0.05	
 Hemoglobin (g/L)	128.7 ± 25.8	122.1 ± 27.3	0.06	
 Platelet (*109/L)	238.5 ± 94.4	241.1 ± 108.6	0.84	
 Albumin (g/L)	28.4 ± 2.7	19.6 ± 3.2		
 eGFR (mL/min/1.73m2)	71.1 ± 32.3	65.6 ± 35.6	0.25	
 24-h proteinuria (g/24 h)	6.7 ± 4.9	11.4 ± 6.8	 < 0.01	
 TG (mmol/L)	2.9 ± 1.5	3.0 ± 2.0	0.71	
 TCHO (mmol/L)	7.2 ± 2.2	8.7 ± 3.4	 < 0.01	
 HDL-C (mmol/L)	1.2 ± 0.4	1.3 ± 0.8	0.76	
 LDL-C (mmol/L)	4.3 ± 1.9	5.1 ± 2.4	 < 0.01	
Coagulation parameters	
 D-Dimer (mg/L)	0.8 [0.3, 2.6]	1.0 [0.4, 2.8]	0.38	
 FIB (mg/L)	4.3 ± 1.9	4.7 ± 1.6	0.13	
 FDP (mg/L)	5.9 [2.0, 13.6]	7.6 [3.2, 17.6]	0.50	
 Protein C (%)	131.1 ± 42.1 (n = 9)	131.5 ± 53.4 (n = 15)	0.98	
 Protein S (%)	86.1 ± 27.0 (n = 9)	86.6 ± 31.2 (n = 15)	0.97	
 Antithrombin (%)	87.7 ± 20.4 (n = 8)	80.2 ± 19.7 (n = 13)	0.41	
Prior treatment	
 Steroid (n, %)	31 (36.9%)	106 (46.5%)	0.13	
 Immunosuppressor (n, %)	25 (29.8%)	81 (35.5%)	0.33	
 Rituximab (n, %)	2 (2.4%)	2 (0.9%)		
 Diuretic (n, %)	25 (29.8%)	110 (48.2%)	 < 0.01	
 Albumin (n, %)	5 (6%)	56 (24.6%)	 < 0.01	
 Anticoagulant (n, %)	14 (16.7%)	67 (29.4%)	0.01	
Autoimmunity disease	
 Autoimmunity disease (n, %)	10 (11.9%)	8 (3.5%)	0.03	
 Lupus anticoagulant (n, %)	8 (9.5%)	5 (2.2%)	0.03	
 Anticardolipin/Anit-β2 glycoprotein1 antibodies	3 (3.6%)	4 (1.8%)	0.95	
Other factors related to thromboembolism	
 Moderate to severe edema (n, %)	33 (60.0%)	180 (89.1%)	 < 0.01	
 Former hospitalization/long time bedrest (n, %)	12 (15.4%)	73 (32.3%)	 < 0.01	
 Confirmed/suspected neoplasms (n, %)	6 (7.1%)	9 (3.9%)	0.24	
Time of the occurrence of thromboembolic events	
 Concurrent with diagnosis (n, %)	34 (40.5%)	58 (25.6%)	0.01	
 A week within renal biopsy (n, %)	2 (2.4%)	16 (7.0%)	0.12	
 Subsequent follow-up within 6 months (n, %)	32 (38.1%)	93 (41.0%)	0.65	
 Subsequent follow-up after 6 months (n, %)	16 (19.0%)	60 (26.4%)	0.18	
RBC red blood cell, eGFR estimated glomerular filtration rate, FIB Fibrinogen, FDP fibrinogen degradation product, TG triglycerides, TCHO total cholesterol, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol

The two groups were similar with respect to sex, age, BMI, hemoglobin, RBCs, platelets, eGFR (71.1 ± 32.3 vs. 65.6 ± 35.6 ml/min/1.73 m2) and smoking history. Compared with the low-albumin group, the high-albumin group had a significantly lower level of 24-h proteinuria (6.7 ± 4.9 vs. 11.4 ± 6.8 g/24 h, P < 0.01). The coagulation parameters were comparable between the two groups.

As for prior treatment, patients with NS in the high-albumin group had a significantly lower rate of diuretic, albumin, and anticoagulant use. No significant differences were found between the two groups in the usage of steroids and immunosuppressants. However, patients with NS in the high-albumin group had a significantly higher rate of autoimmune disease (11.9% vs. 3.5%, P = 0.03) and positive LA(positive lupus anticoagulant) (9.5% vs. 2.2%, P = 0.03). Among patients in the high-albumin group in our study, 4 were diagnosed with simple systemic lupus erythematosus (SLE) and 3 were diagnosed with SLE and secondary antiphospholipid syndrome (APS) along with positive LA.

Pathological classifications

Table 2 shows the pathological classifications of the two groups. No significant difference was found between the two groups in any pathological type. Table 2 Pathological classifications of patients with NS and relevant thromboembolic events

Pathological classifications	Albumin ≥ 25 g/L (n = 84)	Albumin < 25 g/L (n = 228)	P value	
MN (n, %)	39 (46.4%)	117 (51.3%)	0.45	
non-typical MN	2 (5.1%)	11 (9.4%)	0.49	
Anti-PLA2R positive MN (n, %)	18 (69.2%)	74 (93.0%)	 < 0.01	
MCD (n, %)	5 (6.0%)	25 (11.0%)	0.13	
DN (n, %)	4 (4.8%)	4 (1.8%)	0.23	
Renal amyloidosis (n, %)	6 (7.1%)	5 (2.2%)	0.10	
LN (n, %)	4 (4.8%)	4 (1.8%)	0.23	
FSGS (n, %)	1 (1.2%)	10 (4.4%)	0.08	
Other (n, %)	4 (4.8%)	5 (2.2%)		
Unknown (n, %)	21 (25.0%)	58 (25.4%)		
Total (n, %)	84 (100%)	228 (100%)		
1. MN membranous nephropathy, PLA2R M-type Phospholipase A2 receptor, MCD minimal change disease, DN diabetic nephropathy, LN lupus nephritis, FSGS focal segmental glomerular sclerosis

2. The percentage of anti-PLA2R positive MN were calculated among all the patients with MN along with performed anti-PLA2R antibody test

In patients with NS in the high-albumin group, the leading pathological type was MN (39, 46.4%), followed by renal amyloidosis (6, 7.1%), MCD (minimal change disease) (5, 6.0%), LN (lupus nephritis) (4, 4.8%), DN (diabetic nephropathy) (4, 4.8%), FSGS (focal segmental glomerular sclerosis) (1, 1.2%), and others (4, 4.8%). The pathological diagnosis of 21 cases (25.0%) remained unknown. In patients with NS in the low-albumin group, MN was also the most common type (117, 51.3%), followed by MCD (25, 11.0%), FSGS (10, 4.4%), renal amyloidosis (5, 2.2%), DN (4, 1.8%), LN (4, 1.8%) and others (5, 2.2%), while 58 types (25.4%) remained unknown. Several patients did not receive renal biopsies due to anticoagulation treatment for the encountered thromboembolic events. In addition, the incidence rate of anti-PLA2R-positive MN in the high-albumin group was significantly lower than that in the other group (69.2% vs. 93.0%, P < 0.01).

Thrombus types

Table 3 shows the thrombus types in the two groups. The distribution of thrombus types was comparable between the two groups. The most common thromboembolic events were PE (28, 33.3% in the high-albumin group vs. 92, 40.4% in the low-albumin group), followed by DVT (19, 22.6% vs. 37, 16.2%) and RVT (11, 13.1% vs. 27, 11.8%). Table 3 Thrombus types of patients with NS and relevant thromboembolic events

Thrombus types	Albumin ≥ 25 g/L
(n = 84)	Albumin < 25 g/L (n = 228)	P value	
DVT (n, %)	19 (22.6%)	37 (16.2%)	0.22	
PE (n, %)	28 (33.3%)	92 (40.4%)	0.25	
RVT (n, %)	11 (13.1%)	27 (11.8%)	0.77	
PE + DVT (n, %)	4 (4.8%)	24 (10.5%)	0.06	
PE + RVT (n, %)	2 (2.4%)	10 (4.4%)	0.42	
RVT + DVT (n, %)	4 (4.8%)	8 (3.5%)	0.61	
PE + DVT + RVT (n, %)	4 (4.8%)	5 (2.2%)	0.31	
ATE (n, %)	10 (11.9%)	22 (9.6%)	0.56	
Other (n, %)	2 (2.4%)	3 (1.3%)		
Total (n, %)	42 (100%)	111 (100%)		
DVT deep vein thrombosis, PE pulmonary embolism, RVT renal vein thrombosis, ATE arterial thrombus embolism

Discussion

Our study reviewed 312 patients with NS and relevant thromboembolic events, and 26.9% of them developed thromboembolic events with relatively high albumin levels. All patients received a full dose of anticoagulation therapy after being diagnosed with thromboembolic events. Both groups were similar with respect to clinical characteristics and coagulation parameters, except for 24-h proteinuria. In the high-albumin group, no significant difference in clinical characteristics was found that could directly contribute to their thrombus risk compared with the other group. MN was found to be the most common type of NS among patients with relevant thromboembolic events in both groups. Anti-PLA2R-positive MN in the high-albumin group was significantly less common than it was in the other group. Furthermore, patients in the high-albumin group had a significantly higher rate of autoimmune disease.

Among patients with NS, previous research found that those with MN were at greatest risk for the development of thromboembolism, regardless of their albumin levels. The other common histologies include MCD and FSGS [5]. Patients with primary MN have an increased risk of VTE, greater than that attributable to NS alone. In the presence or absence of NS, there is also a close correlation between the risk of VTE and the histological diagnosis in patients with glomerulonephritis, while patients with MN are still at the highest risk [6]. Moreover, primary MN was found to increase the risk of arterial thromboembolic events, which were measured as cardiovascular events [7].

In our study, MN was still the most common type in patients with NS and relevant thromboembolic events. Interestingly, anti-PLA2R-positive MN in patients with NS with high albumin levels was significantly less common than the other group in our study. Anti-PLA2R antibody level is thought to be associated with clinical disease activity. Patients with high anti-PLA2R antibody levels reached remission of proteinuria significantly later than those with low anti-PLA2R antibody levels. While anti-PLA2R antibody levels fell over time in one cohort of patients with spontaneous remission, they remained high in patients without reductions in proteinuria [8]. Furthermore, anti-PLA2R antibody was found to be an independent risk factor for VTE [9]. However, our study showed that several patients even developed thromboembolic events when their anti-PLA2R antibody levels fell. This suggests that even during remission of MN, there is still a risk of thromboembolic events. However, little is known about the reason behind the high thrombus risks of patients with MN. In patients with MN, recent research found that patients with Th17 (T helper lymphocyte-17)-mediated inflammation had more VTE [10]. Overall, we should pay attention to patients with MN among all patients with NS for their high thrombus risks, regardless of their albumin levels or anti-PLA2R antibody levels.

Moreover, patients with NS with high albumin levels in our study had a significantly higher rate of autoimmune disease, mainly APS and SLE. In APS or SLE, NS could be the clinical manifestation of renal involvement. APS is an autoimmune disorder characterized by recurrent ATE or VTE and/or recurrent spontaneous abortion, along with persistently elevated levels of antiphospholipid antibodies (aPLs). Research has shown that 30%–40% of patients with SLE were positive for aPLs. Of patients with both SLE and positive aPLs, approximately half were found to develop APS within 10–20 years [11]. APS alone is usually classified as primary APS, and APS in the presence of SLE or another autoimmune disorder is classified as secondary APS. The kidney is a major target organ in APS, both primary and secondary. Renal involvement is a well-recognized manifestation of APS, characterized by thrombosis at any vascular site in the kidney [11]. Furthermore, although glomerulonephritis is rarely reported in patients with APS, MN is still the most commonly reported glomerulonephritis in patients with primary APS [12].

In patients with SLE, LA is an important biomarker for hypercoagulability. LA is an acquired autoantibody of the immunoglobulin G (IgG) or immunoglobulin M (IgM) type that acts on platelet factor III, inhibiting the generation of the prothrombin activator complex [13]. One study showed a significant association between the presence of thrombotic complications in SLE and the presence of LA [14]. Among patients with SLE, those with positive LA have a higher incidence of ATE and VTE than those without [13]. This finding shows the importance of screening for secondary factors of NS and identifying autoimmune diseases in patients with NS. For those who were previously diagnosed with SLE, examinations of LA and aPLs are crucial.

Additionally, our study showed that patients with NS with high albumin levels had a significantly lower rate of anticoagulant usage, in accordance with the consensus that a low serum albumin level can increase VTE risk. A study found that prophylactic anticoagulants significantly decreased the risk of thromboembolic events in patients with NS but was also associated with more bleeding episodes, although the association was not significant [15]. There were multiple reasons that prophylactic anticoagulation failed to prevent thromboembolic events in our patients, including inadequate anticoagulation, initiation of prophylactic anticoagulation before thorough screening for thromboembolic events, suspension prophylactic anticoagulation before renal biopsy. The 2021 KDIGO clinical practice guideline used 25 g/L of serum albumin level as the threshold to initiate prophylactic anticoagulant in patients with MN [2]. To provide a personalized prophylactic anticoagulation decision in patients with MN, Lee et al. constructed a tool to estimate the likelihood of benefit based on the patient’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio [16]. For other pathological types, the serum albumin threshold for anticoagulation initiation has not been clearly set, although the level between 20 and 25 g/l in combination with one or more risk factors is agreed upon by most studies [2, 17]. However, our study found that there was still a rather high percentage of patients with NS who developed thromboembolic events with relatively high albumin level, indicating that the level of albumin may not be the only criterion for giving prophylactic anticoagulants.

Interestingly, as an emerging treatment for MN and some other pathological classifications, rituximab may also play a part in thromboembolic events. In our study, one patient with NS with a high albumin level developed thrombus right after rituximab usage and encountered thrombus recurrence after rituximab retreatment. Several articles also reported cases of thrombus during or right after rituximab treatment for other diseases [18–20]. However, they all failed to confirm whether the thrombi were directly related to rituximab. The relationship between thrombus and rituximab still requires further research.

Finally, we found that the percentage of our patients with albumin ≥ 28 g/L was somewhat high (40, 12.8%). Among all 40 of the patients, 17 (43%) were diagnosed with MN, and 5 (12.5%) were diagnosed with autoimmune disease. Therefore, physicians should consider the potential risk of a hypercoagulable state in patients with MN or combined autoimmune disease, even with albumin ≥ 28 g/L. The albumin concentration threshold for anticoagulation therapy may be higher in patients with MN or comorbid autoimmune disease.

Our study has several limitations. First, this study was lack of control group and had a small population size. All the patients were hospitalized, so there were no outpatients, which could lead to a certain degree of selection bias. Second, all our patients were diagnosed with thrombus while being screened for thromboembolic events during hospitalization, yet the thrombi could have formed before hospitalization without anyone knowing. Third, a rather high percentage of our patients (25.3%) were without renal biopsies. Finally, we failed to collect protein C, protein S, and antithrombin in the majority of cases because they were not performed routinely. Multicenter clinical studies with larger populations are needed in the future.

Conclusions

In general, our study found that there is still a high risk in patients with NS and relatively high albumin levels to develop thromboembolic events. MN is the most frequent type of NS among patients with relevant thromboembolic events, regardless of their albumin level. During remission of MN, there is still a risk of thromboembolic events. Therefore, adequate screening and prevention may be necessary for these patients.

Abbreviations

NS Nephrotic syndrome

MN Membranous nephropathy

PLA2R M-type phospholipase A2 receptor

VTE Venous thrombus embolism

ATE Atrial thrombus embolism

eGFR Estimated glomerular filtration rate

DVT Deep venous thrombosis

PE Pulmonary embolism

RVT Renal venous thrombosis

FDP Fibrinogen degradation product

FIB Fibrinogen

LA Lupus anticoagulant

SLE Systemic lupus erythematosus

APS Antiphospholipid syndrome

MCD Minimal change disease

LN Lupus nephritis

DN Diabetic nephropathy

FSGS Focal segmental glomerular sclerosis

Acknowledgements

Not applicable.

Authors’ contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yi-meng Liu and Shuang Gao. The first draft of the manuscript was written by Yi-meng Liu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

CAMS Innovation Fund for Medical Sciences (2019-I2M-5–046).

The General Program (Key Program, Major Research Plan) of National Natural Science Foundation of China (82,070,731).

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved and has been granted an exemption from requiring written informed consent by Peking University First Hospital Clinical Research Ethics Committee. (2023–741).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yi-meng Liu and Shuang Gao contributed equally to this work.
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