Lupus Nephritis: Current Perspectives and Moving Forward

Lichtnekert, Julia; Anders, Hans‐Joachim; Lech, Maciej

doi:10.2147/jir.s363722

Cited by 9 publications

(4 citation statements)

References 143 publications

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“… 14 31 32 It may be that current treatments reduce disease activity but do not alter the underlying pathophysiologic mechanisms of the disease and, therefore, its progression. 33 34 In this context, new treatments or better implementation of available treatment strategies are needed, especially for patients with more severe or frequently relapsing disease. Data from recent trials of add-on therapies in LN have shown favourable short-term results in terms of remission and relapse, but their potential role in DM remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

Παναγιωτόπουλος¹,

Kapsia²,

Michelakis³

et al. 2023

RMD Open

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ObjectiveA preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify aspects of DM criteria in LN, assess DM achievement in a real-world setting and examine potential DM predictors and long-term outcomes.MethodsWe collected clinical/laboratory and histological inception cohort data from biopsy-proven LN patients (82% females) with ≥72 months follow-up at two joint academic centres. Specific criteria for 24-hour proteinuria, estimated glomerular filtration rate (eGFR), renal flares and glucocorticoids dose were set at three time frames (months 0–12, 13–60 and 72) to assess DM. In the first model, DM was achieved if patients fulfilled all four criteria at all three time frames (achievers). In the second model, the continued glucocorticoids reduction criterion was excluded. Logistic regression analyses were performed. Possible different trends in DM achievement between past and recent decades were also investigated.ResultsDM was achieved by 60% of patients, increased to 70% when glucocorticoids excluded from DM criteria. 24-hour proteinuria at 9 months predicted DM achievement (OR 0.72, 95% CI 0.53 to 0.97, p=0.03), but none of baseline characteristics. Among patients with >72 month follow-up, non-achievers had worse renal outcomes (flares, >30% proteinuria increase, eGFR decline) than achievers at the end of follow-up (median 138 months). Patients diagnosed between 1992 and 2005 were found to have significantly lower percentages of DM achievement and met less often the glucocorticoids dose reduction criterion in all three time frames, compared with those diagnosed between 2006 and 2016 (p=0.006 and p<0.01, respectively).ConclusionsDM was achieved by only 60% of LN patients in a real-life setting, partly due to lack of glucocorticoids dose target attainment, while DM failure was associated with worse long-term renal outcomes. This may imply limitations in the effectiveness or implementation of current LN treatments, supporting the need for novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

Παναγιωτόπουλος¹,

Kapsia²,

Michelakis³

et al. 2023

RMD Open

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“…LN is usually accompanied by elevated anti-dsDNA antibodies and anti-nuclear antibodies (ANAs) as well as signs of renal insufficiency [26][27][28]. Therefore, we detected urinary protein concentrations and the above two serum indicators at 4, 6, 10, and 12 weeks in LN mice.…”

Section: Biochemical and Pathological Alterations Of Ln Micementioning

confidence: 97%

Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis

Li,

Yao,

Guo

et al. 2024

Cell Death Dis

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Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression. Mesangial cells (MCs) are intrinsic cells in the kidney that can regulate capillary blood flow, phagocytose apoptotic cells, and secrete vasoactive substances and growth factors. Previous studies have shown that various types of inflammatory cells can activate MCs for hyperproliferation, leading to disruption of the filtration barrier and impairment of renal function in LN. Here, we characterized the heterogeneity of kidney cells of LN mice by single-nucleus RNA sequencing (snRNA-seq) and revealed the interaction between macrophages and MCs through the CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, macrophages modulated the proliferation and migration of MCs through this ligand–receptor interaction. In LN mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC proliferation and reduced urinary protein levels. Together, our findings indicated that targeting the CXCL12/DPP4 axis with linagliptin treatment may serve as a novel strategy for the treatment of LN via the CXCL12/DPP4 axis.

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“…Conversely, in the absence of timely and standardized therapeutic interventions, renal function typically undergoes progressive deterioration, culminating in recurrent episodes and a markedly heightened mortality rate. The precise pathogenesis leading to LN is currently uncertain, but it is unequivocally established that aberrations in cell death and cellular debris clearance, augmented nucleic acid recognition and interferon signaling, genetic anomalies, lymphocytic dysregulation, aberrant complement system activation, and perturbed cytokine milieu collectively contribute to the initiation and progression of both SLE and LN ( Lichtnekert et al, 2022 ). It has been suggested that augmented programmed cell death and impaired neutrophil-specific clearance of apoptotic remnants, resulting in the breakdown of immune tolerance to nuclear autoantigens, may constitute the incipient trigger for systemic autoimmunity in SLE ( Yang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of tacrolimus in the treatment of lupus nephritis

Wang,

Zhou,

Niu

et al. 2024

Front. Pharmacol.

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Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus’ regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice.

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Lupus Nephritis: Current Perspectives and Moving Forward

Cited by 9 publications

References 143 publications

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis

Mechanism of tacrolimus in the treatment of lupus nephritis

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