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Letter
Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study
  1. Savino Sciascia1,2,
  2. Jinoos Yazdany3,
  3. Maria Dall'Era3,
  4. Roberta Fenoglio2,
  5. Massimo Radin1,
  6. Ishita Aggarwal3,
  7. Maria J Cuadrado4,5,
  8. Karen Schreiber5,6,7,
  9. Antonella Barreca8,
  10. Mauro Papotti8,
  11. Dario Roccatello1,2
  1. 1 Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
  2. 2 SCU Nephrology and Dialysis(ERKnet member), S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
  3. 3 Division of Rheumatology, Russell/Engleman Research Center, University of California, San Francisco, California, USA
  4. 4 Lupus Unit, Department of Rheumatology, Guy's and St Thomas' Hospital, London, UK
  5. 5 Department of Thrombosis and Haemophilia, Guy's and St Thomas' Hospital, London, UK
  6. 6 King Christian X’s Rheumatology Hospital, Graasten, Denmark
  7. 7 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen, Denmark
  8. 8 Division of Pathology, Department of Medical Sciences, University of Turin, Turin, Italy
  1. Correspondence to Dr Savino Sciascia, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin, Turin 10154, Italy; savino.sciascia{at}unito.it

https://doi.org/10.1136/annrheumdis-2018-214559

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    The management of lupus nephritis (LN) and concomitant thrombotic microangiopathy (TMA), with or without antiphospholipid antibodies (aPL), remains controversial, and few studies are available to inform clinical management.1–4

    The purpose of this multicentre retrospective study was to analyse the impact of anticoagulation (vitamin K antagonists (VKAs) and/or heparins) in addition to conventional immunosuppression on kidney outcomes (assessed at 12 months, according to the Kidney Disease: Improving Global Outcomes-KDIGOguidelines5) in patients with biopsy-proven LN and concomitant TMA.

    Data source, population and statistical analysis are detailed in the online supplementary material 1. Anticoagulation was considered if given for at least three consecutive months after TMA diagnosis.

    We retrospectively identified 97 patients with biopsy-proven LN and TMA (2007–2017). See online supplementary table 1 for clinical and demographic characteristics. Laboratory parameters were collected at the time of the biopsy. The mean age of patients was 38.9±15.2 years (13–69) and 85 females (87.6%). Most had proliferative LN (class IV in 84.5%). In total, 42 (43%) patients presented with acute and 55 (57%) with features of chronic TMA. All patients had received treatment with standard immunosuppressants (55% mycophenolate, 39% cyclophosphamide, 6% other regimen) and steroids. At 12 months, complete response (CR) was observed in 37 patients (38.1%), partial response (PR) in 22 (22.6%) and no response (NR) in 38 (39.1%). Sixty-one patients (62.9%) were aPL positive and 37 (38.1%) of these patients received anticoagulation with a VKA and/or heparins. Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months (3-12).

    We observed a higher rate of clinical response (CR/PR, together or computed separately) in patients who received anticoagulation (CR in 22 (59.46%), PR in 7 (18.91%); NR in 8 (21.62%)) compared with those without (CR in 15 (25.0%), PR in 15 (25.0%); NR in 30 (50%)), p<0.01) (table 1).

    View this table:
    Table 1

    Univariate analysis of patient characteristics by kidney outcome

    When limiting the analysis on the 61 patients with aPL, we observed a higher rate of complete response in those receiving anticoagulation (patients receiving anticoagulant therapy: CR in 22 (59.46%), PR in 7 (18.91%); NR in 8 (21.62%)) versus patients not receiving VKA/heparins (CR in 8 (30.77%), PR in 7 (26.92%); NR in 8 (34.62%),p=0.046) (figure 1).

    Figure 1
    Figure 1

    Comparison of kidney outcomes between patients receiving anticoagulation and those without ((A) all 97 patients; (B), limiting to patients positive for antiphospholipid antibodies). aPL, antiphospholipid antibodies; CR, complete response; LN, lupus nephritis; NR, no response; PR, partial response;TMA thrombotic microangiopathy.

    After multivariate analysis, aPL positivity (any) (β=1.23,OR 2.4;95% CI 1.2 to 7.3;p=0.03), anti-dsDNA positivity (β=1.98,OR 12.8; 95% CI 3.0 to 71.3; p=0.002) and chronic features of TMA (β=1.31,OR 3.0; 95% CI 1.2 to 17.5; p=0.04) were all associated with no kidney response.

    When limiting the analysis to aPL-positive patients, after adjusting for type of immunosuppressant therapy and LN class, variables that were significantly associated with CR+PR were features of acute TMA rather than chronic (β=1.95, OR 8.62; 95% CI 1.4 to 97.1; p=0.03) and the use of VKA/heparins (β=1.21 OR 2.1; 95% CI 1.02 to 16.2; p=0.046).

    In summary, in our study the use of anticoagulation was associated with any response to treatment at 1 year, in line with the fact that about 60% of the patients with CR received VKA or heparins. Similarly, when limiting the analysis to patients with aPL, we observed a rate of any response (either CR+PR) as high as 66% in patients receiving anti-coagulant treatment compared with those receiving immunosuppression alone (34%).

    Despite its limitations (the relatively short duration of follow-up to gauge the relapse rate; lack of standardised protocol for LN treatment; the use of anticoagulation agents was not randomised but based on the treating physicians’ judgement), this study represents the largest available multicentre cohort of real-life systemic lupus erythematosus patients with biopsy-proven LN and concomitant TMA.

    To conclude, in patients with concomitant LN and TMA, the use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool; the presence of aPL, anti-dsDNA antibodies and chronic features of TMA was associated with poorer kidney outcomes.

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    Footnotes