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Lupus Nephritis: The Past, The Present and The Future

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Dr Jai Radhakrishnan, USA    28 December 2018

  • Global prevalence of systemic lupus erythematosus (SLE) (per 1,00,000) - North America: 4.8-78.5; Europe: 25-91; Australia: 19-63; China: 30-50; Japan: 8-18. India has 6,00,000 to 1,000,000 patients.
  • Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis (LN): clarification of definitions, and modified National Institutes of Health activity and chronicity indices - New definitions: mesangial hypercellularity, and crescents (cellular, fibrocellular and fibrous); The term “Endocapillary proliferation” replaced by endocapillary hypercellularity; Class IV-S and IV-G eliminated; Active and chronic designations replaced by activity and chronicity indices.
  • Systemic lupus and pregnancy - Women to be counseled to delay pregnancy until a complete remission of LN has been achieved; Cyclophosphamide, mycophenolate mofetil (MMF), ACE inhibitors and ARBs should not be used during pregnancy; Hydroxychloroquine to be continued during pregnancy; LN patients who become pregnant while being treated with MMF should be switched to azathioprine; If LN patients relapse during pregnancy, they should receive treatment with corticosteroids and, depending on the severity of the relapse, azathioprine.
  • LN in children - Children with LN should receive the same therapies as adults with LN, with dosing based on patient size and GFR.
  • Unmet needs in proliferative LN - Induction: Remission rates 50%; Side effects/Corticosteroid-sparing; Resistant lupus; Maintenance: Reduction of flares; Corticosteroid side effects.
  • Multitarget therapy for induction treatment - A study found that multitarget therapy consisting of tacrolimus, MMF and steroid provided superior efficacy compared with intravenous cyclophosphamide (CYC) plus steroid as induction therapy for LN (Ann Intern Med. 2015;162(1):18-26).
  • Multitarget therapy for maintenance treatment - Multitarget therapy as a maintenance treatment for LN (tacrolimus, MMF and steroid) led to a low renal relapse rate and fewer adverse events compared to azathioprine plus steroid (J Am Soc Nephrol. 2017;28(12):3671-8).
  • A recent multicenter, randomized controlled study revealed that combined immunosuppressive treatment (CIST) is superior to routine CYC only therapy in LN (Clin Rheumatol. 2018 Nov 28).
  • Efficacy of rituximab in refractory LN - Weidenbusch et al have shown that rituximab induces remission of LN in patients who have not achieved remission with standard therapies.
  • Although survival in SLE patients has improved, a significant number of patients experience chronic disease including LN.
  • Initial therapy for LN - MMF = CYC: Multitargeted therapy.
  • Resistant disease - Switch to alternative regimen, rituximab, plasmapheresis, IVIg.
  • Maintenance therapy - MMF or azathioprine (MMF may be superior in patients who have remitted); Continue hydroxychloroquine.
  • Novel targets and personalized medicine approaches will help.

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