Under The Progress Of Pathological Classification Of Patients With Lupus Nephropathy, How Can Biological Agents Turn The Tide, Achieve Complete Remission Of Kidneys, And Increase Serum Complement

Lupus nephritis (LN) is a common clinical manifestation and the main cause of death of systemic lupus erythematosus (SLE). It is more common in women, and the male-to-female ratio is 1: (9~10). Although men are not a high-incidence group of LN, studies have shown that male LN patients have an earlier onset age and a longer disease course. In the same age group, male LN patients have more severe renal damage and a worse long-term prognosis than females [1]. Due to the extremely high recurrence rate of LN, if the patient does not follow the doctor's advice to stop the drug, it may cause irreversible damage to the kidney.

Click to cistanche tubulosa examine for kidney disease

LN is a kidney disease caused by SLE. When SLE patients have proteinuria, hematuria, or decreased renal function, they can be diagnosed as LN. Generally, the incidence of LN in men is lower than that in women, but the time from onset to kidney damage is shorter, and it is often accompanied by damage to other organs, among which heart, lung, liver damage, central lesions, and polyserositis are more common, treatment effect and prognosis are also poor [1]. Recently, with the improvement of the understanding of LN and the application of renal biopsy techniques, the diagnosis rate of male LN patients has also increased significantly.

LN treatment includes two stages of remission induction and maintenance therapy, and its goal is to reduce urinary protein, improve patient prognosis, protect the kidney, prevent or delay renal function deterioration, and improve the quality of life of LN patients, highlighting the "people-oriented" medical concept[ 2,3]. But the reality is unsatisfactory. Although the standard treatment of hormones plus immunosuppressants can control the disease, long-term use of hormones has a significant risk of infection, and the recurrence rate of LN is high. It will be uncontrolled, and even end-stage renal disease (ESRD) will occur, and the fatality rate is extremely high. How to achieve renal remission and control the disease while reducing the use of hormones, the advent of belimumab is tantamount to "sending charcoal in the snow".

Belimumab is a fully human monoclonal antibody that targets and binds to soluble B lymphocyte stimulating factor through intravenous administration, inhibits the proliferation and differentiation of B cells, and induces the apoptosis of autoreactive B cells, thereby reducing serum levels of Autoantibodies to achieve the purpose of treatment of LN [4]. The currently well-known BLISS-LN study is a 104-week, randomized, double-blind, placebo-controlled phase III clinical trial for patients with LN, evaluating the efficacy and safety of belimumab in the treatment of LN. In this study, patients were randomly assigned in a 1:1 ratio to receive belimumab (10 mg/kg) or a placebo group, both of which were combined with standard treatment. The primary endpoint at Week 104 was primary efficacy renal response (PERR) at Week 104, and the primary secondary endpoint was the complete renal response (CRR). Patients were also assessed for time to kidney-related events or death.

The results showed that at week 104, more patients in the belimumab group achieved the primary endpoint PERR (43.0% vs. 32.3%, OR 1.55, 95% CI (1.04, 2.32), p=0.0311) and reached the key For secondary endpoints, the differences were statistically significant. Compared with the placebo group, the proportion of patients receiving belimumab treatment achieved and maintained PERR and CRR was higher, and the belimumab group significantly reduced the risk of kidney-related events within 104 weeks. In terms of safety endpoints, the belimumab group was comparable to the placebo group [5]. Italian scholars reported 2 cases of female type Ⅳ LN, both of whom were given MMF as induction therapy, but could not be tolerated due to gastrointestinal toxicity. Subsequently, belimumab combined with low-dose MMF was effective as induction therapy, and two patients achieved complete renal response [6]. After the recommendation of the 2019 EULAR/ERA-EDTA updated guidelines [7] and the 2019 "Chinese Guidelines for the Diagnosis and Treatment of Lupus Nephritis" [3].

In 2021, the Guidelines for Improving Kidney Disease Outcomes Global (KDIGO) also recommends that belimumab combined with conventional treatment can be used for the initial treatment of LN [8]. The National Medical Products Administration (NMPA) officially approved the marketing of belimumab on February 9, 2022. So far, belimumab has become the first and only biological target approved for the treatment of adults, children with SLE, and adult LN. to the preparation. Among them, adult indications have been included in national medical insurance, providing the possibility for more LN patients to benefit from biological agents.

The current prevalence of LN in the world is 0-241/100,000, China The prevalence of LN ranks second in the world, with more than 1 million people suffering from it. The male-to-female prevalence ratio is 1: (9~10). Although the symptoms of male LN patients are not typical, the pathological types are severe and the prognosis is poor, so more attention should be paid to clinical work.

For the treatment of male LN, first of all, because the symptoms of such patients are atypical, to avoid misdiagnosis, clinicians should create conditions to actively carry out laboratory tests and renal biopsy for early detection and timely diagnosis and treatment. Secondly, the patient should be instructed to have good compliance during the period of taking the medicine, and not to stop the medicine on his own to avoid relapse. Because every time LN relapses, more immune complexes will be deposited in the kidneys and other organs, which will aggravate organ damage, accelerate the disease process, and increase the difficulty of treatment.

Finally, for LN, a single drug or a combination of two drugs may be effective, but a combination of drugs is required for full remission. The reason is that LN is a systemic disease that needs to be blocked and treated from multiple targets and multiple pathways. The addition of belimumab to the traditional treatment plan can more comprehensively block multiple targets, thereby reducing the dosage of hormones and reducing the recurrence rate of the disease. In this way, belimumab can be described as "icing on the cake".

for more information:ali.ma@wecistanche.com