Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus and a significant cause of CKD and ESRD in young adults, particularly women. The ISN/RPS 2003 classification of LN, updated in the 2018 revision published by Bajema et al. in Kidney International, provides the standardized histopathological framework that guides therapeutic decisions based on class, activity, and chronicity of glomerular lesions.
ISN (International Society of Nephrology) co-developed the original 2003 classification system with the Renal Pathology Society, and the 2018 revision incorporated refined criteria for distinguishing focal from diffuse proliferative LN and introduced clearer definitions of activity and chronicity indices. The prognostic significance of chronicity indices, including interstitial fibrosis and tubular atrophy, was substantiated in retrospective cohort analyses published in Kidney International and the Journal of the American Society of Nephrology.
The LUNAR trial evaluated rituximab added to standard mycophenolate mofetil and corticosteroid induction in proliferative LN (Rovin et al., Arthritis & Rheumatism, 2012) and did not reach its primary endpoint, highlighting the complexity of study design in LN. Subsequent breakthrough results came from the BLISS-LN trial (Furie et al., New England Journal of Medicine, 2020), demonstrating that belimumab added to standard therapy reduced the risk of renal flares and improved the primary efficacy renal response at two years.
The AURORA 1 trial (Rovin et al., Lancet, 2021) demonstrated that voclosporin, a calcineurin inhibitor analogue with a more predictable pharmacological profile, combined with mycophenolate mofetil and low-dose steroids, achieved significantly higher complete renal response rates at 52 weeks compared to standard therapy. The NOBILITY trial evaluated obinutuzumab, a type II anti-CD20 monoclonal antibody, also showing superior complete renal response at 76 weeks.
The International Society of Nephrology has emphasized the need for biomarker-guided treatment monitoring in LN. Urinary biomarkers including TWEAK/Fn14, MCP-1, and ALCAM have been investigated in prospective studies as markers of renal flare activity. ISN-affiliated investigators have contributed to the development and validation of the BILAG-based composite lupus assessment (BICLA) and kidney-specific response criteria used in contemporary LN clinical trial design.