ArticleInternal and emergency medicine2026
Refractory lupus nephritis: national multicenter study.
Article in Internal and emergency medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Refractory lupus nephritis (LN) remains a major therapeutic challenge and a leading cause of progression to end-stage kidney disease (ESKD) in systemic lupus erythematosus (SLE). To characterize a large multicenter cohort of refractory LN, evaluate therapeutic strategies used after non-response, and determine long-term renal outcomes. Multicenter longitudinal cohort including 68 patients with refractory LN from several Spanish centers. Refractoriness was defined according to the GLOSEN consensus as failure to reduce proteinuria by > 25% or worsening of proteinuria and/or renal function after ≥3 months of triple immunosuppressive therapy. Demographic, clinical, histological, therapeutic and outcome data were collected. The cohort included 68 patients (61 women), mean age 34.5 [27-45] years. Renal biopsy showed predominantly proliferative classes (III-IV and mixed forms). Extrarenal involvement was frequent, mainly articular (82.3%), hematological (70.6%) and cutaneous (60.3%). Before non-response, most patients had received corticosteroids (98.5%), mycophenolate mofetil (82.3%), antimalarials (91.2%) and cyclophosphamide (36.8%). Non-response occurred after 16.1 ± 9.5 months and was due to persistent proteinuria (61.8%), worsening renal function (25%) or both (13.2%). Over 12 months, creatinine remained stable, from 0.96 to 1.02 mg/dL (p = 0.726), C3 increased from 56.3 to 85.55 mg/dL (p < 0.001), C4 rose from 0.82 to 1.02 mg/dL (p < 0.001), while proteinuria decreased from 1.9 ± 0.5 to 0.57 ± 0.24 g/24 h (p < 0.001). After treatment modification or intensification-including tacrolimus (39.7%), rituximab (27.9%) and belimumab (27.9%), 41 patients (60.3%) achieved LN remission during a mean follow-up of 59.7 ± 46 months. Ten patients progressed to ESKD (6 requiring hemodialysis and 4 undergoing kidney transplantation). Infections were the most frequent complication (30.9%). Therapeutic escalation allowed LN remission in a substantial proportion patients with refractory LN; however. the risk of progression to ESKD remained high. These findings highlight the need for earlier recognition of non-response and more effective treatment strategies to prevent irreversible renal damage.
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