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. 2024 Jul 1;35(7):955-958.
doi: 10.1681/ASN.0000000000000365. Epub 2024 Apr 9.

Immunosuppression Withdrawal in Patients with Lupus Nephritis: When, How, and for Whom Will It Be Safe?

Eleni Frangou  1   2 , Hans-Joachim Anders  3 , Ingeborg M Bajema  4 , Y K Onno Teng  5   6 , Ana Malvar  7 , Brad H Rovin  8 , Andreas Kronbichler  9
Affiliations

Immunosuppression Withdrawal in Patients with Lupus Nephritis: When, How, and for Whom Will It Be Safe?

Eleni Frangou et al. J Am Soc Nephrol. .
No abstract available

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Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/E631.

Figures

Figure 1
Figure 1
Proposed algorithm for immunosuppression continuation or slow and gradual withdrawal in patients with lupus nephritis in complete or partial clinical remission. At 12 months from diagnosis, patients are on maintenance immunosuppression and antimalarials to maintain control of disease activity and on renin-angiotensin system inhibition for kidney protection. At this time point, patients with complete clinical remission should continue immunosuppression as immune memory is long lasting. In patients who have achieved partial clinical remission by 12 months and in whom proteinuria has been continuously improving, the same immunosuppression should be continued as lesions may need a longer time to completely resolve. However, in patients with partial clinical remission but in whom proteinuria has not been further improving, a repeat biopsy should be considered to evaluate whether the plateau in proteinuria is due to chronic damage or because the activity index has not improved or has increased. If the plateau in proteinuria is due to chronic damage, current immunosuppression should be continued; if activity is not improving or is worsening, treatment modification/intensification should be considered. Thirty-six to 42 months from diagnosis, when intrarenal immunological remission can be achieved even without proteinuria reaching response criteria, we propose performing a repeat biopsy in all patients (irrespective of proteinuria levels) to gain information about specific active and chronic lesions. In patients with an activity index of more than 2, immunosuppressant withdrawal should not be attempted. In patients with complete histologic remission (activity index of 0), immunosuppressant withdrawal should be attempted under close observation. The first medication to taper off and discontinue is steroids. After determining the patient is stable off steroids, mycophenolate mofetil or azathioprine should be discontinued next, slowly decreasing the dose over 6 months. Data on the outcome of patients with an activity index of 1 or 2 are lacking. In these patients, the same immunosuppression scheme should be continued. Persistently positive anti-dsDNA, low serum complement, and endocapillary hypercellularity in repeat biopsy are associated with a flare risk. Extrarenal lupus manifestations should be taken into account. For patients who have not achieved histologic remission and continue immunosuppression, a repeat biopsy should be considered every 24 months until either the activity index becomes 0 or the patient develops sufficient chronic damage that risk of immunosuppression exceeds the benefit of bringing the activity under control. At this point, immunosuppression may be withdrawn, unless extrarenal disease necessitates ongoing treatment. Hydroxychloroquine should be maintained in all patients and nephroprotective measures should be optimized in patients with chronic damage. The algorithm does not apply to patients who did not achieve complete or partial clinical remission by 12 months from diagnosis. §Continue immunosuppression if the activity index is improving. §§Modify/intensify immunosuppression and evaluate adherence to therapy if the activity index has not improved from baseline biopsy or is increasing. *In repeat kidney biopsies, more than ten nonglobally sclerosed glomeruli and immunofluorescence are required. #A repeat biopsy should be considered every 24 months until either activity index becomes 0 or sufficient chronic damage has accumulated such that the risk of continued immunosuppression exceeds the benefit of treating any remaining activity. Complete and partial clinical remission: Normal or stable serum creatinine with inactive urine sediment in the absence of extrarenal lupus activity with either proteinuria <0.5 g/d or 50% reduction in proteinuria and to <3 g/d, respectively. Serological remission: Negative anti-dsDNA antibodies and normal serum complement levels. Intrarenal immunological remission: Absence of glomerular immunoglobulins or complement by immunofluorescence microscopy. Complete histologic remission: Activity index of 0 at repeat biopsy. anti-dsDNA, anti-double stranded DNA antibodies; HCQ, hydroxychloroquine.
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References

    1. Houssiau FA Vasconcelos C D’Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis. 2010;69(1):61–64. doi: 10.1136/ard.2008.102533 - DOI - PubMed
    1. Anders H-J, Saxena R, Zhao M, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7. doi: 10.1038/s41572-019-0141-9 - DOI - PubMed
    1. Malvar A Alberton V Lococo B, et al. Remission of lupus nephritis: the trajectory of histological response in successfully treated patients. Lupus Sci Med. 2023;10(1):e000932. doi: 10.1136/lupus-2023-000932 - DOI - PMC - PubMed
    1. Perez-Arias AA Márquez-Macedo SE Pena-Vizcarra OR, et al. The influence of repeated flares in response to therapy and prognosis in lupus nephritis. Nephrol Dial Transplant. 2023;38(4):884–893. doi: 10.1093/ndt/gfac304 - DOI - PubMed
    1. Fanouriakis A Kostopoulou M Cheema K, et al. 2019 update of the joint European league against rheumatism and European renal association-European dialysis and transplant association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713–723. doi: 10.1136/annrheumdis-2020-216924 - DOI - PubMed

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