What Are The Advancements in The Treatment Of Lupus Nephritis?
Mar 14, 2024
Lupus nephritis (LN) is kidney damage caused by systemic lupus erythematosus (SLE). About 50% of SLE patients have clinical manifestations of renal damage, and renal biopsy shows that renal involvement is almost 100%. LN is one of the important causes of end-stage renal failure in my country [1].
Click to Cistanche for kidney disease
March 14 this year is World Kidney Day, and the theme is Kidney Health for All: Promoting Equitable Medical Services and Optimized Drug Treatment Practices. In the past year, in the field of LN, what drug research progress is worthy of attention?
The content of this article will be based on a high-scoring review of CKD management published in the British Medical Journal (BMJ) [2], taking stock of the cutting-edge advances in LN treatment. Come and take a look!
Voclosporin
The AURORA 1 (NCT03021499) study is a double-blind, randomized, multicenter, placebo-controlled Phase III clinical study, which confirmed that Voclosporin combined with mycophenolate mofetil (MMF) and low-dose steroids has good efficacy and safety in the treatment of LN [3 ].
Following the AURORA 1 study, 216 patients entered the AURORA 2 study and continued to receive Voclosporin treatment for 2 years, aiming to evaluate the long-term safety, tolerability, and clinical efficacy of Voclosporin.
The results showed that the adverse event (AE) characteristics of the Voclosporin and the placebo groups were similar to those of the AURORA 1 study and well tolerated. The mean corrected glomerular filtration rate (eGFR) in both groups was stably maintained within the normal range.
At 2 years of treatment, the eGFR slope was -5.4ml/min/1.73m2 in the placebo group and -0.2ml/min/1.73m2 in the Voclosporin group.
After 3 years of treatment, proteinuria continued to improve in the Voclosporin group, and the complete renal remission rate was higher than that in the placebo group. Studies have shown that Voclosporin is safe and effective in the long-term treatment of LN [4].
In addition, the VOCAL study (NCT05288855) is a double-blind, placebo-controlled, dose-escalation study designed to evaluate the efficacy, safety, and pharmacokinetics of voclosporin in the treatment of adolescent LN for 24 weeks. It is expected to be initially completed in 2024[5].
After the VOCAL study, patients entered the VOCAL-EXT study and continued to receive Voclosporin treatment for 12 months, aiming to evaluate the long-term efficacy and safety of Voclosporin in the treatment of adolescent LN. The study is expected to be initially completed in 2026 [6].
Atacicept
The APRIL-LN study (NCT00573157) is a randomized, double-blind, placebo-controlled Phase II/III clinical study designed to evaluate the efficacy and safety of Atacicept combined with standard of care (SoC) in patients with active LN. However, the study was terminated early due to serious complications in the patient [7].
In addition, the COMPASS study (NCT05609812) is a randomized, double-blind, multinational, multi-center, placebo-controlled phase III clinical study designed to evaluate the efficacy and safety of Atacicept in the treatment of active LN. It is expected to be initially completed in 2026[8].
Anifrolumab
The TULIP-LN study (NCT02547922) is a randomized, double-blind, multi-center, placebo-controlled phase II clinical study designed to evaluate the efficacy and safety of the type I interferon receptor antibody anifrolumab in the treatment of active grade III/IV LN. sex.
Although the study did not reach the primary endpoint, compared with placebo, Anifrolumab intensive treatment (IR) improved various endpoints including complete renal response (CRR) [9].
In addition, the IRIS study (NCT05138133) is a randomized, double-blind, multi-center, placebo-controlled Phase III clinical study designed to evaluate the efficacy and safety of Anifrolumab in the treatment of adults with active proliferative LN. It is expected to be initially launched in 2026. Complete[10].
Lanalumab
The SIRIUS-LN study (NCT05126277) is a randomized, double-blind, parallel-group, multi-center, placebo-controlled phase III clinical study designed to evaluate the efficacy and safety of Ianalumab in the treatment of active LN based on compliance with the SoC. and tolerability, which is expected to be initially completed in 2027 [11].
secukinumab
The SELUNE study (NCT04181762) is a randomized, double-blind, parallel group, placebo-controlled phase III clinical study designed to evaluate the efficacy of subcutaneous (s.c.) 300 mg secukinumab combined with SoC compared with placebo combined with SoC. efficacy, safety and tolerability in patients with chronic LN, but the study was terminated early due to invalid analysis [12].
Obinutuzumab
The NOBILITY study (NCT02550652) is a randomized, double-blind, multi-center, placebo-controlled Phase II clinical study designed to evaluate the efficacy and safety of Obinutuzumab combined with SoC compared with placebo combined with SoC in the treatment of LN.
The results showed that after the 125 included patients were randomly assigned and received blind treatment, compared with the placebo group, patients in the Obinutuzumab group had better scores at week 52 [22 (35%) vs. 14 (23%)] and week 104 [ 26 (41%) vs. 14 (23%)], the CRR ratio was significantly higher, reaching the primary endpoint and key secondary endpoints of the study, and the safety profile was good.
The results of this study show that Obinutuzumab can help improve the clinical response of LN without increasing the incidence of serious adverse events [13].
In addition, the REGENCY study (NCT04221477) is a randomized, double-blind, multi-center, placebo-controlled phase III clinical study designed to evaluate the efficacy and safety of obinutuzumab in the treatment of LN (2003 ISN/RPS, level III or IV). The research is expected to be initially completed in 2024 [14].
ACTHar Gel
The ACTHar study (NCT02226341) is an open-label prospective randomized controlled study designed to evaluate the efficacy and safety of ACTHar gel in the treatment of proliferative LN, and is expected to be initially completed in 2024 [15].
How Does Cistanche Treat Kidney Disease?
Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.
Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.
Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.
Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.
Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.
Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.
Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.
In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.
In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.
