Treatment of lupus nephritis: consensus, evidence and perspectives

Mok, Chi Chiu; Teng, Y K Onno; Saxena, Ramesh; Tanaka, Yoshiya

doi:10.1038/s41584-023-00925-5

Cited by 54 publications

(43 citation statements)

References 148 publications

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“…Complete histologic response in Bx2 is associated with lower relapse rate and preserved eGFR in the long term. [3][4][5][6][7][8][9] Mycophenolate associated with Belimumab from the beginning allowed in 90% of patients to achieve a CHR compared to 50% in the placebo group: this would suggest a positive difference in favor of the SOC + Belimumab combination, showing that inflammation was probably controlled earlier in this group.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 The massive use of corticosteroids is, even nowadays, one of the factors that most contributes to chronic organ damage during the treatment of LN, although its use is increasingly restricted in all current treatment guidelines. 8 Since several pathways of the immune system are usually activated, the treatment of LN is prolonged and requires the frequent combination of more than one immunosuppressant to achieve remission. 9 Therefore, treatment should then be aimed at preserving renal function but, due to the potential side effects of the numerous drugs used, another priority should be given to avoid as much toxicity as possible.…”

Section: Discussionmentioning

confidence: 99%

“…Histological activity may persist in an inapparent way in 30 to 40% of patients with sustained clinical remission after several years of immunosuppressive treatment. [3][4][5][6][7][8][9][10][11][12] This study included 20 patients (10 in MMF + PBO group and 10 in MMF + Belimumab) who, having participated in the BLISS LN trial and its OLE phase, were rebiopsied after receiving immunosuppressive treatment for 43.6 (15.8) months (mean ± SD) from Bx1 so as to assess 113 ± 28.6 98.5 ± 28.4 100.6 ± 28,7 U-PCR a 3.7 ± 1.8 3.2 ± 2.9 3.9 ± 2.5 Bx1 class…”

Section: Discussionmentioning

confidence: 99%

“…However, this limited scenario has been expanded in recent years with the approval of Belimumab and Voclosporin for the treatment of LN, as both drugs were shown to be able to increase the likelihood of renal response when associated with SOC. [6][7][8][9][10][11][12][13] Belimumab's mechanism of action (neutralizing B-cell activating factor, with the subsequent down-regulation of B-cell function and decrease in autoantibody production), together with an excellent safety profile, turns it into a valuable therapeutic option associated with SOC. 6 In this study, patients in the Belimumab group received Belimumab from the start of treatment and for at least 30 consecutive months.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A “post-hoc” analysis of participants in the BLISS-LN and open label extension study belonging to a single center

Malvar,

Alberton,

Recalde

et al. 2023

Lupus

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Background: Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes. Research Design and Study Sample: In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response. Ten patients treated with MMF + Placebo versus 10 receiving MMF + Belimumab, were compared evaluating the complete clinical (CCR) and complete histological response (CHR) and the flares in each group. Results: All the patients in the Belimumab group showed a CCR and 7 in the Placebo one; CHR was found in 9 and 5 patients of the Belimumab and Placebo group, respectively. None of the patients in the Belimumab group flared meanwhile two of the Placebo one did it. Conclusions: Although the number of patients is insufficient to be able to draw unquestionable conclusions, adding Belimumab to the standard of care treatment with MMF would seem to increase the possibility of achieving a CCR, CHR, and a lower rate of relapses during treatment and long follow-up.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A “post-hoc” analysis of participants in the BLISS-LN and open label extension study belonging to a single center

Malvar,

Alberton,

Recalde

et al. 2023

Lupus

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Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus

Yen,

Wang,

Hsu

et al. 2024

JAMA Netw Open

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ImportanceLupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is).ObjectiveTo investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes.Design, Setting, and ParticipantsThis multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023.ExposuresIndividuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching.Main Outcomes and MeasuresThe Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups.ResultsFrom 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers.Conclusions and RelevanceIn this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.

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Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response

Fava,

Wagner,

Guthridge

et al. 2024

Arthritis & Rheumatology

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ObjectiveAutoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership (AMP) LN longitudinal cohort to identify serological biomarkers of LN histological classification and treatment response, and how these biomarkers change over time based on treatment response.MethodsPeripheral blood samples were collected from 279 SLE patients undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead‐based assays (Bio‐Rad Bioplex 2200) and anti‐C1q by ELISA at the time of biopsy (baseline) and at 3‐, 6‐, and 12‐months post‐biopsy. Clinical response was determined at 12 months.ResultsProliferative LN (ISN/RPS class III/IV+V, n=160) was associated with higher concentrations of anti‐C1q, ‐chromatin, ‐dsDNA, and –ribosomal P autoantibodies compared to non‐proliferative LN (classes I/II/V/VI, n=108). Anti‐C1q and‐dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti‐C1q levels predicted complete response (AUC, 0.72; p, 0.002) better than baseline proteinuria (0.59; 0.21). Furthermore, all autoantibody levels, except for anti‐La/SSB, decreased over 12 months in proliferative, but not membranous, LN patients with a complete response.ConclusionsBaseline levels of anti‐C1q and ‐dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti‐C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in proliferative LN patients.image

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Treatment of lupus nephritis: consensus, evidence and perspectives

Cited by 54 publications

References 148 publications

Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A “post-hoc” analysis of participants in the BLISS-LN and open label extension study belonging to a single center

Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A “post-hoc” analysis of participants in the BLISS-LN and open label extension study belonging to a single center

Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus

Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response

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