Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE.

OBJECTIVE: Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort. METHODS: The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling. RESULTS: A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD. CONCLUSIONS: In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD.

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Systemic lupus Erythematosus activity and Hydroxychloroquine use before and after end-stage renal disease.

BACKGROUND: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. METHODS: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development. RESULTS: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission. Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p = 0.005), CNS manifestations (6 [20%] vs 1 [4%], p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p = 0.029). CONCLUSIONS: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.

Treatment of antiphospholipid syndrome beyond anticoagulation.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). At the present time, treatment is primarily focused on anticoagulation. However, there is increasing awareness of the mechanisms involved in APS pathogenesis, which has led to the trial of novel therapies targeting those mechanisms. Following a brief review of the etiopathogenesis of and current management strategies in APS, this paper focuses on the evidence for these potential, targeted APS treatments, e.g., hydroxychloroquine, statins, rituximab, belimumab, eculizumab, defibrotide, sirolimus, and peptide therapy.

Venous thromboembolism in chronic kidney disease: epidemiology, the role of proteinuria, CKD severity and therapeutics.

The worldwide prevalence of chronic kidney disease is 10-15 % of the adult population, is rising and increases susceptibility to venous thromboembolism (VTE). In this narrative review we discuss the underlying evidence behind the association of VTE/CKD and examine the role of worsening CKD stage, proteinuria, and the risk of recurrent VTE. As CKD may alter therapeutic options we discuss the role of emerging therapies, the non-vitamin K oral anticoagulants (NOAC), in the treatment of VTE.