The main hypothesis of the study is that there may be a difference in the risk of AVF/AVG dysfunction between SLE and non-SLE patients due to endothelial activation, apoptosis, and atherogenesis [6–8]. To the best of our knowledge, previous research addressing the risk of vascular access dysfunction in SLE patients receiving HD had not analysed the rate of dysfunction in SLE patients after 1 year [4, 5]. The observation period in this study was over a 10-year duration. The results have shown that SLE patients on HD had a significantly higher risk of developing AVF/AVG dysfunction during the long-term period follow up, especially after the first year, 1st-year-to-10th-year, and overall periods.
Shafi et al. conducted a study where 66.6% of 36 SLE patients developed VAT at 1 year as compared to 38.9% of 36 non-SLE patients (P < 0.05) and the odds ratio of VAT in SLE patients was 3.1 (95% confidence interval = 1.2, 8.2) . Plantinga et al. carried out a study on 117,836 incident adult and pediatric ESRD patients with a one-year follow-up period and revealed that SLE patients who started treatment with a permanent vascular access on first dialysis were less likely to experience patency loss than non-SLE patients within the first year (43.8% vs. 55.0%, respectively). This outcome may be due to the nature of the population in this study where SLE-ESRD patients were found to less likely have comorbid conditions (such as diabetes, congestive heart failure, peripheral vascular disease) and to smoke than the other ESRD patients . Cuen-Ojeda et al. conducted a retrospective review of AVFs created between 2008 and 2017 where 134 patients were identified. When compared to patients with chronic diseases such as diabetes, hypertension, and idiopathic ESRD, SLE patients have an increased risk of developing AVF patency loss within the first 6 months of follow-up .
The possible pathogenetic mechanisms associated with a higher risk of vascular access thrombosis (VAT) include the Virchow triad, which consists of stasis, hypercoagulability, and endothelial injury . Stasis is the condition of reduced blood flow within the vascular access. Hypoalbuminemia is a predisposing factor for stasis and is usually attributed to nephrotic syndrome or disease exacerbation in SLE, both of which may lead to vascular access dysfunction [11, 12]. Hypercoagulability in SLE may be attributed to lupus-specific antibodies (aPLs), which can lead to VAT through possible mechanisms such as atherogenesis, and endothelial activation . Inflammation in SLE may also increase certain procoagulant factors that may increase the risk of developing VAT . Endothelial activation and damage is commonly observed in SLE patients. Different mechanisms have been proposed to explain the prevalence of endothelial dysfunction in SLE . Atehortúa et al. pointed out that different components of the immune system seem to participate in endothelial injury, such as autoantibody production and immune complex formation, which is characterized by an increase in the expression of adhesion molecules, production of pro-inflammatory cytokines and prothrombotic factors, oxidative stress upregulation, and abnormal vascular tone modulation . The structural damage and attenuation of endothelial function in vascular access may lead to their loss of viability and integrity, which may eventually result in possible long-term vascular access failure.
VAT is a common complication that develops in majority of HD patients with an arteriovenous access, accounting for 65%-85% cases of permanent vascular access loss . Antiphospholipid (aPL) antibodies, which include anticardiolipin (aCL) antibodies and lupus anticoagulants (LAC), are the most common acquired blood protein defects causing thrombosis [17, 18]. In SLE patients, there were 30%-40% who tested positive for aPL  and the prevalence of positive LAC activity ranged between 11–30% and positive aCL activity between 17–40% [20–22].
Grönhangen-Riska et al. reported for the first time the presence of aCL in the HD population . Phillips et al. showed that the aCL presence had no significant relationship with thrombotic events , but Prakash et al. showed that HD patients with elevated IgG-aCL titers have higher odds of recurrent AVG thrombosis . Haviv found that vascular access occluders had higher mean IgG and IgM aCL levels than non-occluders (24.47 and 8.39 IU/mL in occluders [p < 0.0226] vs. 8.45 and 3.59 IU/mL in non-occluders [p < 0.05]). These results indicated that HD patients, especially those with recurrent access occlusion episodes, may be associated with elevated IgG aCL levels, which could be applied to predicting the occlusive status of HD patients . Shafi et al. observed SLE patients on HD during a 1-year period where patients with positive aCL antibodies had a statistically significantly higher rate of VAT (83.3%) as opposed to patients with negative aCL antibodies (33.3%) .
Quereda et al. found that 30% of HD patients exhibited LAC activity compared to 11% patients on conservative treatment (P < 0.02). Patients with LAC also exhibited a higher incidence of thrombosis than patients without it (23% vs. 13%, respectively) . Brunet et al. found that VAT was significantly more frequent in patients with LAC than in patients without LAC (62% vs. 26%, respectively; P = 0.01) . The Lupus in Minorities: Nature vs. Nurture (LUMINA) study found a significant correlation between thrombosis events and shorter disease duration, implying such events occur early in the course of SLE. In addition, the presence of LAC, smoking, older age, disease activity over time, and higher mean daily glucocorticoid dose were identified as risk factors in the development of venous thrombosis . Bataille et al. determined the aPL prevalence and risk factors in 192 HD patients where at least one type of aPL was found in 19.8% of patients, of which 74% had only LAC. There was a significant association between VAT history and aPL presence (hazard ratio = 3.03; 95% confidence interval = 1.69, 4.42; P < 0.001) where aPL presence, especially LAC, is associated with VAT in HD patients .
García-Martín et al. tested both aCL and LAC activity in 51 HD patients where 31% had aCL activity, 22% had LAC activity, and 37% had LAC and/or aCL activity. . Wahl et al. conducted a study where patients with SLE and LAC have approximately six times greater risk for venous thrombosis (odds ratio = 5.61; confidence interval = 3.80, 8.27; P < 0.0015) than patients without LAC, whereas patients with SLE and aCL have approximately two times greater risk for venous thrombosis (odds ratio = 2.17; confidence interval = 1.51, 3.11; P < 0.05) than patients without aCL .
Numerous studies have shown that SLE patients have increased risks of developing MACE, acute myocardial infarction, and stroke [33–35]. However, this study did not demonstrate SLE patients having a higher risk of developing MACE, AMI, and stroke than non-SLE patients. Differences in demographic characteristics in the SLE population of this study may account for the different outcomes and further studies may be needed to reevaluate the relationship between SLE, HD, and the aforementioned adverse events.
There are several limitations of this study that should be noted. This is a retrospective study and utilized a database where laboratory markers as potential prognostic variables cannot be analysed. It was also conducted in a single country (Taiwan) where all of the participants were of Chinese ethnicity. The prognosis and outcomes between SLE and non-SLE patients with different ethnicities is unknown, and may limit the generalization of results. The number of patients with AVG listed in the database were also too few and was combined with the number of patients with AVF for the final analysis. In spite of the aforementioned limitations, this study enrolled the largest number of SLE patients in analysing vascular access and has the longest observation period of 10 years.
AVF/AVG dysfunction in SLE patients is of crucial clinical relevance since it worsens the quality of life and is a clinical challenge for the healthcare professionals in HD units. Additional randomized large-scale prospective studies are needed in the future to confirm the results in this study and to also address the following important issues: (1) the roles of autoantibodies and other additional factors contributing to pathogenesis of AVF/AVG dysfunction, (2) the role of antiplatelet or anticoagulation in preventive strategy against VAT, and (3) the interaction between SLE, hemostasis, and immunological system in the pathogenesis of thromboembolism in SLE patients under maintenance HD.
In conclusion, there were significantly higher incidence rates of AVF/AVG dysfunction in SLE patients than non-SLE patients during long-term follow-up period (especially after 1 year and during the 1st-to-10th year period) in this study. A multi-disciplinary approach may be considered to improve vascular access patency in SLE patients. In order to extend the durability of a permanent vascular access and prevent further complications, such as VAT, early diagnostic evaluation of aCL and LAC activity in ESRD patients is recommended.