The influence of repeated flares in response to therapy and prognosis in lupus nephritis

Abstract

Background Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney, and patient prognosis. Methods All patients from a biopsy-proven LN cohort between 2 008 and 2 018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare, or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the eGFR, doubling of serum creatinine, end-stage kidney disease, and patient survival. Results A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare, and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria, and hematuria among groups. The NIH chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. Conclusions A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the NOBILITY Trial

“…Disease flare is a major risk factor for loss of kidney function, and prevention of flares is an important therapeutic goal for lupus nephritis management. 7,30 With every lupus nephritis flare, damage to the kidney accumulates. 31 By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage.…”

“…Treatment with obinutuzumab reduced the risk of lupus nephritis flare by 57%. Disease flare is a major risk factor for loss of kidney function, and prevention of flares is an important therapeutic goal for lupus nephritis management 7,30 . With every lupus nephritis flare, damage to the kidney accumulates 31 .…”

“…4,5 It is also clear that lupus nephritis relapse portends a worse long-term kidney and patient prognosis. [6][7][8] Preservation of long-term kidney function is a major therapeutic goal in lupus nephritis. As lupus nephritis clinical trials generally span 12 to 24 months, there has been an effort to identify study endpoints that serve as surrogate markers for long-term kidney health.…”

“…Despite numerous advances in the treatment of active lupus nephritis, including the regulatory approvals of belimumab in 2020 and voclosporin in 2021, 2,3 complete renal response (CRR) rates remain low 4,5 . It is also clear that lupus nephritis relapse portends a worse long‐term kidney and patient prognosis 6–8 …”

Clinical significance of exostosin 1 in confirmed and suspected lupus membranous nephropathy

“…Cox proportional hazards regression models determined predictive factors for CR to treatment after adjustment for other factors such as eGFR and numbers of LN flare. 19 …”