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Lupus nephritis: New predictors of renal outcomes and treatment strategies.

Comment on: Moroni G, Gatto M, Tamborini F, et al. Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis. Ann Rheum Dis 2020; 79:1077-1083. Link: https://ard.bmj.com/content/79/8/1077

Commented by: Luís Sousa Inês, MD, PhD. CHUC Lupus Clinic, Rheumatology Department. Centro Hospitalar Universitário de Coimbra (CHUC). Coimbra, Portugal. Faculty of Health Sciences. University of Beira Interior. Covilhã, Portugal.

Lupus nephritis (LN) is the most common severe organ involvement of Systemic lupus erythematosus (SLE), affecting 25 to 60% of patients. In developed countries, the estimated 5-year risk of end-stage renal disease (ESRD) is 11%, and in patients with diffuse proliferative LN up to 40% of patient can develop ESRD in the long-term, despite standard-of-care treatment of LN.1 So far, tested composite and single short-term variables did not univocally function as long-term prognostic markers of chronic kidney disease (CKD). Identification of reliable short-term predictors is an unmet need in clinical practice to help guiding treatment decisions. In this study, Moroni et al tested the ability of the EULAR/ERA-EDTA definition of response 2 to therapy at 1 year, along with covariates, to predict the long-term development of CKD. The study included 381 patients, mostly Caucasians, from 3 Italian referral centres, with biopsy-proven LN that received induction treatment between 1970 and 2016 and with a median follow-up of 10.7 years. In this cohort, 26% and 58% achieved partial and complete renal response, respectively, one year after starting induction treatment for LN. Independent predictors of CKD in multivariable analysis, were: no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547). This study may have been underpowered to discriminate between complete and partial renal response to prevent CKD.

These results provide evidence for the importance of achieving early response to treatment of LN to maximize the chances of long-term renal survival. There is still an unmet need for identifying early predictors of response to induction treatment that can guide the clinician to adjust therapy in order to optimise the chance of reaching renal remission up to 12 months. The rate of complete renal response at 1 year remains low and new therapies and treatment strategies are needed.

References:

  1. Tektonidou M, Dasgupta A, Ward MM. Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971–2015. A Systematic Review and Bayesian Meta-Analysis. Arthritis Rheum 2016; 68:1432-1441.
  2. 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; 79:713-723.
  3. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002; 46: 2121-31.
  4. Ward M, and Tektonidou MG. Belimumab as Add-on Therapy in Lupus Nephritis. N Engl J Med 2020; 383:1184-1185.
  5. Atisha-Fregoso Y, Malkiel S, Harris KM, et al. CALIBRATE: A Phase 2 Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Arthritis Rheumatol 2020 Aug 4. [Epub ahead of print] doi: 10.1002/art.41466.