Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide range of clinical manifestations. Lupus nephritis (LN), one of the most severe complications affecting organs, is initially diagnosed in 40–60 % of patients with SLE [[1], [2], [3]]. The incidence and severity of LN are notably higher among pediatric patients aged 10 to 13 years [4], with approximately 5–20 % of those affected progressing to end-stage renal disease, which carries significant morbidity and mortality risks [5]. Numerous studies have indicated that individuals with LN often experience inadequate disease control, thereby increasing the likelihood of developing end-stage kidney disease. This situation not only imposes a substantial economic burden on patients but also adversely impacts the mental health of pediatric populations [[6], [7], [8]].
LN primarily arises from renal injury caused by the deposition of circulating or immune complexes. Additionally, a small proportion of SLE affects the kidneys through non-immune complex mechanisms, such as lupus interstitial nephritis or renal vascular disease [9,10].
Therefore, the use of immunosuppressants is recommended for the management of LN. Options include glucocorticoids, cyclophosphamide, mycophenolate mofetil (MMF), and tacrolimus (TAC) [11,12]. Flare occurs in 25–50 % of patients with LN who attain either complete or partial renal remission following immunosuppressive therapy [[13], [14], [15]]. In recent years, evidence has demonstrated that multi-target therapy incorporating glucocorticoids, MMF, and TAC is more effective than the use of individual immunosuppressive agents. Furthermore, employing multiple agents at lower doses can enhance therapeutic efficacy while minimizing adverse reactions [16,17]. For decades, multi-target strategies have served as the foundation for anti-rejection therapy following solid organ transplantation [[18], [19], [20]]. Controlled clinical trials have established MMF as a viable option for sustaining renal responses after the induction therapy for LN [21,22]. The relative specificity of MMF for activated lymphocytes, along with its anti-proliferative and anti-fibrotic effects, underscores its efficacy in the treatment of LN [23]. The calcineurin inhibitor TAC is a potent suppressor of T-cell proliferation. Numerous studies have demonstrated that calcineurin inhibitors exert protective effects on glomerular podocytes, independent of their immunosuppressive properties [24,25]. These findings may elucidate the underlying mechanism of the anti-proteinuric effect of TAC, which has been observed in the management of glomerular diseases, particularly those characterized by membranous lesions [26,27]. Previous research has demonstrated that TAC is effective, well-tolerated, and safe for both the induction and maintenance treatment of LN [[28], [29], [30]].
In recent studies involving MMF, hydroxychloroquine (HCQ), and prednisone regimens, the mycophenolic acid (MPA)-area under the concentration-time curve between 0 h and 12 h (AUC0–12h) has been shown to correlate with clinical responses in patients with LN and may serve as a predictor for disease status. However, there is a lack of relevant research examining whether MPA-AUC0–12h is associated with clinical outcomes in the context of multi-target therapy. The objective of this study was to explore the relationship between MPA-AUC0–12h and renal remission or lupus activity in pediatric LN patients undergoing multi-target therapy, aiming to establish an effective threshold for MPA-AUC0–12h that can predict clinical responses.
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