Antiphospholipid Syndrome Nephropathy Research Articles

#1707 Antiphospholipid antibodies in lupus nephritis

Abstract Background and Aims Antiphospholipid antibodies (aPL) constitute a heterogeneous family of antibodies against anionic phospholipids or phospholipid-binding proteins. They may occur in association with autoimmune diseases, infections, and sometimes in the general population. Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the association of aPL with clinical activity, renal damage, renal activity and outcomes in patients with LN. Method A total of 157 patients (11 male, 146 female, age between 17 and 58 years) with LN were included in this study. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of LN was used to classify the patients into LN subsets. Histopathological renal activity and damage were estimated using the Activity Index (AI) and Chronicity Index (CI), respectively. Levels of anticardiolipin (aCL) antibodies, anti-β2-glycoprotein I (anti-β2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained. Long-term renal outcome was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease stage, after a median follow-up of 20,5 ± 8, 7 years, counting from the occasion of the first renal biopsy. Renal and extra-renal symptoms were analyzed. Patients which have more than one class LN features, were excluded from the study. The treatment includes standard treatment for LN, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, anticoagulants, cyclophosphamide, mycophenolate mofetil, azathioprine. Results LN patients were classified according to the baseline renal biopsies as patients with: minimal mesangial LN (4), mesangial-proliferative LN (30), focal proliferative LN (31), diffuse proliferative LN (48), membranous LN (44). aPL antibodies were detected in 89 (56,69%) patients, aCL antibodies – in 72 (45,86%), anti-β2-GPI antibodies – in 58 (36,94%) and LAC were detected in 46 (29,30%) patients. None of these patients had a concomitant diagnosis of antiphospholipid syndrome nephropathy. Follow-up was similar between aPL-positive and aPL-negative patients. LN patients with positive aPL antibodies had significantly higher SLEDAI (p < 0,05), anti-dsDNA levels (p < 0,05), anti-ribosomal-P antibodies levels (p < 0,05), anti-C1q antibodies (p < 0,05), lower serum C3 (p < 0,005) and C4 (p < 0,05) levels, and higher intensity of complement C3 (p < 0,05) deposits in kidney tissue than the aCL antibody–negative LN patients. aPL-seropositivity was associated with more rapid decline in eGFR (–1,06 mL/min/year compared to –0,45 mL/min/year in aPL-seronegative patients) and showed inferior patient survival (89,8% and 67,9% at 10 and 15 years, respectively, compared to 97,3% and 76% in aPL-seronegative patients). No significant correlation was found between serum aPL antibodies levels and activity or chronicity index scores in renal biopsies at baseline, ANA levels, or age. Conclusion We concluded that aPL-seropositivity are correlated with clinical activity in patients with LN and are associated with inferior long-term patient survival.

Kidney disease in antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

Thrombotic microangiopathy due to primary antiphospholipid syndrome: successful treatment with eculizumab.

Antiphospholipid syndrome nephropathy includes a variety of histological lesions, including thrombotic microangiopathy, which is not included among the diagnostic criteria of antiphospholipid syndrome. Whereas in secondary antiphospholipid syndrome, e.g. to systemic lupus erythematosus, there is emerging evidence of a benefit from complement blockade with eculizumab, optimal treatment of primary antiphospholipid syndrome-associated thrombotic microangiopathy is currently unknown. We report the case of a 36-year-old male patient with primary antiphospholipid syndrome-associated thrombotic microangiopathy, presenting with a clinical picture of atypical hemolytic-uremic syndrome with frequent relapses, treated with eculizumab (four 900mg weekly doses followed by 1200mg fortnightly infusions) leading to resolution of hemolysis, long-term remission and partial kidney function recovery (peak serum creatinine 3.8mg/dL, decreased and stabilized around 2.5mg/dL) over a follow up period of over 2 years.

A Case of Antiphospholipid Syndrome Nephropathy with Acute Thrombotic Microangiopathy After Renal Transplantation.

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

Antiphospholipid syndrome nephropathy: Current knowledge and unanswered questions

The definition of acute and chronic antiphospholipid syndrome (APS) nephropathy was recently updated using a multiphase methodology in the context of the development of the new APS classification criteria. Currently, there is no consensus for the treatment of APS nephropathy, which mainly relies on the general recommendations for the management of APS. Based on evidence from experimental studies and a few clinical studies and case series, targeted treatments such as B-cell depletion, anti-B-cell activating factor antibody, complement inhibition, mammalian target of rapamycin inhibition, and neutrophil extracellular traps or interferon targeting may show promise for the treatment of microvascular manifestations in APS, including APS nephropathy. Validation of the new APS nephropathy definition and/or efforts for improvement in proposed terminology, along with the assessment of the safety and efficacy of potential targeted treatments in randomized controlled trials, are major future research directions. In this review, we summarize the current knowledge of APS nephropathy and discuss unanswered questions.

Anti-β2GPI-domain I antibody is associated with extra-criteria manifestations in a large prospective antiphospholipid syndrome cohort in China

BackgroundAnti-β2GPI-domain I (β2GPI-DI) antibody is pathogenic in patients with antiphospholipid syndrome (APS), but its additional clinical associations and diagnostic value are controversial.MethodsA total of 378 patients were included, of which...

Renal manifestations in connective tissue diseases

Connective tissue diseases (CTD) comprise agroup of inflammatory systemic diseases that can affect various organs. Kidney involvement is frequently associated with significant irreversible damage and often before patients become symptomatic. Screening tests of blood and urine as well as clinical vigilance are therefore essential for all CTDs with possible renal involvement. Akidney biopsy is the gold standard for the diagnosis, prognosis and treatment decisions. Acommon and severe organ involvement in systemic lupus erythematosus (SLE) is glomerulonephritis (GN), also collectively referred to as lupus nephritis (LN). If left untreated LN often leads to end-stage renal failure. The treatment depends on the clinical parameters and histopathology of the renal involvement. Mycophenolate mofetil and cyclophosphamide are potent but nonspecific immunosuppressants which have been available for many years. Recently, new substances specific for LN have also been approved for the first time. Kidney involvement in Sjogren's syndrome has been far less studied. In studies the frequency of renal involvement is still unclear and ranges from 5% to 33%. Tubulointerstitial nephritis (IN) is the typical form of renal involvement which clearly differs from GN in its clinical presentation. Recommendations for treatment are based exclusively on retrospective studies. Arenal crisis in systemic scleroderma (SSc) is a rare but feared complication with ahigh mortality. An antiphospholipid syndrome (APS) nephropathy (APSN) can occur during CTD. These entities are vasculopathies and often thrombotic microangiopathies, which clearly differ from GN and IN in terms of pathophysiology, clinical features and treatment. This article provides an overview of the diversity of the most important renal manifestations of CTDs.

Artemisinin derivative SM934 in the treatment of autoimmune and inflammatory diseases: therapeutic effects and molecular mechanisms.

Artemisinin and its derivatives are the well-known anti-malarial drugs derived from a traditional Chinese medicine. In addition to antimalarial, artemisinin and its derivatives possess distinguished anti-cancer, anti-oxidant, anti-inflammatory and anti-viral activities, but the poor solubility and low bioavailability hinder their clinical application. In the last decades a series of new water-soluble and oil-soluble derivatives were synthesized. Among them, we have found a water-soluble derivative β-aminoarteether maleate (SM934) that exhibits outstanding suppression on lymphocytes proliferation in immunosuppressive capacity and cytotoxicity screening assays with 35-fold higher potency than dihydroartemisinin. SM934 displays significant therapeutic effects on various autoimmune and inflammatory diseases, including systemic lupus erythematosus, antiphospholipid syndrome nephropathy, membranous nephropathy, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and dry eye disease. Here, we summarize the immunomodulatory effects, anti-inflammatory, anti-oxidative and anti-fibrosis activities of SM934 in disease-relevant animal models and present the probable pharmacological mechanisms involved in its therapeutic efficacy. This review also delineates a typical example of natural product-based drug discovery, which might further vitalize natural product exploration and development in pharmacotherapy.

Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy

BackgroundAntiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN. MethodsRetrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed. ResultsThirty patients were included (19 women) with a median age of 40 years (34–52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31–60) mL/min/1.73 m2. Glomerular thrombotic microangiopathy was found in 12/24 cases, fibrous intimal hyperplasia in 12/22 cases and focal cortical atrophy in 17/29 cases. Nineteen patients had moderate to severe interstitial fibrosis (>25%). Six patients developed ESRD at a median follow-up of 6.2 (1.8–9.1) years. The ESRD-free survival rates at 5 and 10 years were 80.0% (95% CI 57.6%–91.4%) and 72.7% (95% CI, 46.9%–87.4%) respectively. None of the histological factors considered was significantly associated with a decrease in eGFR at 12 months. Thrombosis recurrence-free survival was 77.8% (95% CI 48.2%–91.6%) at 10 years. Overall survival was 94% at 10 years (95% CI 65.0%–99.2%). ConclusionsThe renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.

LncRNA MEG3 in Promoting Antiphospholipid Syndrome Nephropathy in Patients with Systemic Lupus Erythematosus

LncRNA MEG3 in Promoting Antiphospholipid Syndrome Nephropathy in Patients with Systemic Lupus Erythematosus

Non-criteria manifestations in primary antiphospholipid syndrome: a French multicenter retrospective cohort study

BackgroundFrom this retrospective study, we aimed to (1) describe the prevalence and characteristics of non-criteria features in primary antiphospholipid syndrome (p-APS) and (2) determine their prognostic value.MethodsThis retrospective French multicenter cohort study included all patients diagnosed with p-APS (Sydney criteria) between January 2012 and January 2019. We used Kaplan-Meier and adjusted Cox proportional hazards models to compare the incidence of relapse in p-APS with and without non-criteria manifestations.ResultsOne hundred and seventy-nine patients with p-APS were included during the study time, with a median age of 52.50 years [39.0; 65.25] and mainly women (n = 112; 62.6%). Among them, forty-three patients (24.0%) presented at least one non-criteria manifestation during the follow-up: autoimmune cytopenias (n = 17; 39.5%), Libman Sachs endocarditis (n = 5; 11.6%), APS nephropathy (n = 4; 9.3%), livedo reticularis (n = 8; 18.6%), and neurological manifestations (n = 12; 27.9%). In comparison to p-APS without any non-criteria manifestations (n = 136), p-APS with non-criteria features had more arterial thrombosis (n = 24; 55.8% vs n = 48; 35.3%; p = 0.027) and more frequent pre-eclampsia (n = 6; 14.3% vs n = 4; 3.1%; p = 0.02). The prevalence of triple positivity was significantly increased in patients with non-criteria features (n = 20; 47.6% vs n = 25; 19.8%; p = 0.001). Patients with p-APS and non-criteria manifestations (n = 43) received significantly more additional therapies combined with vitamin K antagonists and/or antiaggregants. Catastrophic APS (CAPS) tended to be more frequent in p-APS with non-criteria features (n = 2; 5.1% vs none; p = 0.074).The p-APS with non-criteria manifestations had significantly increased rates of relapse (n = 20; 58.8% vs 33; 33.7%; p = 0.018) in bivariate analysis, but in survival analyses, the hazard ratio (HR) of relapse was not significantly different between the two groups (HR at 1.34 [0.67; 2.68]; p = 0.40).ConclusionsThe presence of non-criteria features is important to consider, as they are associated with particular clinical and laboratory profiles, increased risk of relapse, and need for additional therapies. Prospective studies are necessary to better stratify the prognosis and the management of p-APS.

Characteristics and risk factors of retinal vasculopathy in antiphospholipid syndrome.

Retinal vasculopathy including retinal artery occlusion (RAO) or retinal vein occlusion (RVO) was recently found to occur more frequently in antiphospholipid syndrome (APS) patients than non-APS patients. This study aims to investigate the clinical manifestation and risk factors of retinal vasculopathy among APS patients. In this single-center prospective cohort study, we evaluated APS patients with or without retinal vasculopathy during 2018-2020 at Peking Union Medical College Hospital. Clinical variables were compared, and a logistical regression model was built to explore risk factors. Hierarchical cluster analysis using Euclidean distances was applied to identify clusters of variables. A total of 310 APS patients (67.4% female, mean age 38.1years) were included, of whom 18 (5.8%) were diagnosed with retinal vasculopathy (9 with RVO and 9 with RAO). No significant differences were found among most demographic characteristics, clinical manifestations, or antibody profiles. APS-related heart valve disease (odds ratio OR 13.66, 95% confidence interval CI 4.55-40.98), APS nephropathy (OR 12.77, 95% CI 4.04-40.35), and thrombocytopenia (OR 2.63, 95% CI 1.01-6.89) were predictive of retinal vasculopathy. APS-related heart valve disease and nephropathy were also found to be statistically significant predictors in multivariate logistical regression analysis. Non-criteria manifestations were aggregated with retinal vasculopathy from a cluster analysis of variables. Patients with APS-related heart valve disease and nephropathy suffered a higher risk of retinal vasculopathy. The underlying mechanisms of aPL-associated retinal vasculopathy may involve thrombotic microangiopathy, leading to poor prognosis and therapeutic changes.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets.

Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.

Management of Non-criteria Manifestations in Antiphospholipid Syndrome.

To review the available evidence on the management of a variety of non-criteria manifestations in antiphospholipid syndrome (APS), including valvular disease, alveolar hemorrhage, thrombocytopenia, hemolytic anemia, APS nephropathy, skin ulcers, livedo reticularis, cognitive dysfunction, and epilepsy. Current treatment relies on low-level evidence and mainly on expert consensus due to the rarity and the heterogeneity of non-criteria APS manifestations and the diversity in management approaches. Conventional anticoagulation and/or antiplatelet APS treatment do not adequately control most of non-criteria manifestations. Increasing knowledge about the contribution of inflammatory in addition to, or independently of, thrombotic mechanisms in non-criteria APS manifestations provides insight into the potential effect of novel therapies targeting B-cells, mammalian target of rapamycin, neutrophil, and complement or interferon pathways. Existing evidence is limited by lack of high-quality studies. Better understanding of the pathophysiology and clinical phenotypes of APS and well-designed prospective studies of homogenous populations are needed to provide evidence-based recommendations for the management of non-criteria APS manifestations.

Validation of the adjusted global antiphospholipid syndrome score in a single centre cohort of APS patients from Turkey.

The adjusted global antiphospholipid syndrome score (aGAPSS) is a recently developed thrombotic risk assessment score that considers the antiphospholipid antibody (aPL) profile and conventional cardiovascular risk factors. In this retrospective study, we aimed to evaluate the validity of the aGAPSS in predicting clinical manifestations (criteria and extra-criteria) of antiphospholipid syndrome (APS) in a single centre cohort of patients. Ninety-eight patients with APS ± systemic lupus erythematosus (SLE) were classified according to clinical manifestations as vascular thrombosis (VT), pregnancy morbidity (PM) or both (VT + PM). The aGAPSS was calculated for each patient as previously defined. Mean aGAPSS of the cohort was calculated as 10.2 ± 3.8. Significantly higher aGAPSS values were seen in VT (n = 58) and VT + PM (n = 29) groups when compared to PM (n = 11) group (10.6 ± 3.7 vs 7.4 ± 2.9, P = 0.005; 10.7 ± 4 vs 7.4 ± 2.9, P = 0.008, respectively), mainly due to lower frequencies of cardiovascular risk factors in PM. Higher aGAPPS values were also associated with recurrent thrombosis (11.6 ± 3.7 vs 9.9 ± 3.6, P = 0.04). Regarding extra-criteria manifestations, patients with livedo reticularis (n = 11) and APS nephropathy (n = 9) had significantly higher aGAPSS values (12.9 ± 3.4 vs 9.9 ± 3.7, P = 0.02; 12.4 ± 2.9 vs 10 ± 3.8, P = 0.04, respectively). The computed AUC demonstrated that aGAPSS values ≥10 had the best diagnostic accuracy for thrombosis. Our results suggest that patients with higher aGAPSS values are at higher risk for developing vascular thrombosis (either first event or recurrence) and extra-criteria manifestations, especially livedo reticularis and APS nephropathy.

Primary antiphospholipid syndrome associated with anti-phospholipase A2 receptor antibody-positive membranous nephropathy

BackgroundThe kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy.Case presentationA 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission.ConclusionWe report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.

1366 Primary Antiphospholipid Syndrome, Acute Necrotizing Pancreatitis, and IgA Nephropathy in a Young Male: Single Pathogenesis or Rare Association?

INTRODUCTION: Primary Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis, fetal loss and the presence of lupus anticoagulant (LA)/anticardiolipin antibodies. Primary APS is uncommon in males and poses diagnostic difficulties. Primary APS is considered as a rare cause of acute pancreatitis and IgA nephropathy (IgAN). We describe a patient of primary APS (probably the first reported case), who sequentially presented with cerebral venous thrombosis, later with recurrent episodes of acute necrotizing pancreatitis (ANP) followed by IgAN. Despite the initial diagnostic dilemmas, the patient was managed successfully. CASE DESCRIPTION/METHODS: A 30 year old male initially presented with sudden onset headache and generalized seizures. CECT brain revealed cerebral venous thrombosis. Cardiac and Pro thrombotic work up (including ANA and LA) was normal. He was treated with antiepileptics and warfarin. 3 months later, he presented with 3 episodes of acute pancreatitis. Each time the patient was managed conservatively with fluids and analgesics. However the last episode was very severe, CECT abdomen was suggestive of severe ANP with extensive splenic vein thrombosis (SVT). Anti-β2glycoprotein1 antibody test was strongly positive. APS was diagnosed according to revised Sapporo criteria. Low molecular heparin and steroids were started. After 5 months, although the patient recovered from ANP, he presented with hypoproteinemia and renal failure. Urine analysis showed RBC casts and proteinuria. Kidney biopsy showed mesangial IgAN with secondary segmental sclerosis. Patient recovered fully and is on follow up for two years. He is doing fine with low dose steroids, ACE inhibitors and warfarin with regular INR (target 2-3). DISCUSSION: This patient had multiple hospitalizations, all attributable to the rare manifestations of APS. It is perhaps the first case report where APS, ANP and IgAN are described in a single patient. Clinical suspicion can lead to early diagnosis, which makes it easy to manage such patients. Acute pancreatitis is considered as one of the rarest manifestation of APS, which is distinct from autoimmune pancreatitis. Renal biopsy was suggestive of IgAN, which is unusual and distinct from the APS nephropathy. Thrombosis of the pancreatic and renal microcirculation and vasculitis has been postulated as the underlying pathogenesis. To conclude, APS is a rare, yet treatable cause of acute pancreatitis. Urine examination is a must in cases of primary APS, with or without pancreas involvement.

Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics.

Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients. All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications. Two hundred and fifty-six TJRBs-119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics-were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups. TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.

Efficacy and tolerance of selective and non-selective factor Xa inhibitors in the prevention of thrombosis in kidney disease in patients with systemic lupus erythematosus and antiphospholipid syndrome

The use of factor Xa inhibitors is justified in the therapy of thrombosis in antiphospholipid syndrome (APS) and active lupus nephritis (LN). To monitor the efficacy and safety of these drugs, plasma anti-Xa (aXa) activity is determined. Objective : to assess the aXa activity of selective and non-selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and APS depending on how they affect the kidneys. Patients and methods. Clinical and laboratory findings were prospectively analyzed in SLE and APS patients who long received low molecular weight heparins (LMWHs) and selective Xa inhibitors, such as fondaparinux and rivaroxaban. The investigation enrolled 70 patients (54 females and 16 males) aged 39 years (range, 31 to 43 years) with SLE (n=15 (21%)), primary APS (PAPS) (n=10 (14%)), and SLE + APS (n=45 (65%)). Results . Kidney disease was diagnosed in 33 (47%) of the 70 patients. LN was detected in 15 (25%) of the 60 patients: 10 and 5 patients with SLE and SLE + APS, respectively. APS nephropathy (APSN) was manifested by elevated creatinine and urea levels with normal urine sediment and no history of glomerulonephritis and was observed in 18 (33%) of the 55 patients: in 16 with SLE + APS and 2 with PAPS. The therapeutic aXa range of 0.1—1.5 IU/ml was found in 43 (61%) of the 70 patients, low and high aXa activities were seen in 14 (20%) and 13 (19%) patients, respectively. In patients with APSN, the creatinine clearance (CC) depended on aXa levels: the highest CC was noted in patients with aXa >1.5 IU/mL, the lowest CC was in those with aXa <0.9 IU/ mL (p=0.046). The levels of aXa above the therapeutic range were more common in patients taking fondaparinux (9 (31%) out of the 29 patients) than in those using nadroparin (2 (7%) out of the 29 patients) (odds ratio (OR) 1.92; 95% confidence interval (CI), 1.25—2.97; p=0.04). In the fondaparinux group, high aXa was more frequently observed in patients with high SLE activity (7 (47%) out of the 15 patients) than in those with moderate or mild SLE activity (none out of the 7 patients) (OR 1.88; 95% CI, 1.17—3.01; p=0.037) and was unassociated with LN. The highest aXa level with no signs of hemorrhage was 2.08 IU/mL. Conclusion. The level of aXa is a qualitative laboratory marker for the efficacy and safety of LMWHs and fondaparinux. In patients with APS, the enhanced aXa activity of LMWHs and fondaparinux was associated with elevated CC and was not accompanied by hemorrhage. Fondaparinux is an effective and safe anticoagulant for the treatment and prevention of thrombosis in SLE and APS. The therapeutic window for aXa should be extended in these patients.