Diagnosis And Treatment Of ANCA-Associated VasculitisⅣ

Treatment: Induction of remission

Cyclophosphamide-based regimen

The introduction of cyclophosphamide, an alkylating agent, transformed ANCA-associated vasculitis from a disease that was almost universally fatal to one that, while still frequently fatal in the long term, was reversible in most cases. Initial experience with cyclophosphamide involves oral daily regimens (combined with high-dose glucocorticoids), such as rituximab and cyclophosphamide in ANCA-associated vasculitis (RAVE2016 Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA) )-associated vasculitis based on ANCA type.pdf), but the intravenous cyclophosphamide regimen (in combination with glucocorticoids) also has a high likelihood of successful induction of remission.

Click to Cistanche for kidney disease

The CYCLOPS study (2009 Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis a randomized trial) compared intravenous and oral cyclophosphamide in the treatment of generalized ANCA-associated vasculitis and found that intravenous injection and It is associated with an approximately 50% reduction in cyclophosphamide exposure. However, almost 88% of patients in both groups entered remission within 9 months of starting treatment. Both groups of patients received approximately 7.6 g of glucocorticoid therapy equivalent to prednisone during this period, equivalent to an average daily prednisone dose of nearly 28 mg/d. During 4.3 years of off-protocol follow-up, most patients received ongoing remission maintenance therapy with azathioprine and glucocorticoids until 18 months after treatment initiation and then further immunosuppression at the investigator's discretion. Over the entire follow-up period, 40% of patients in the intravenous cyclophosphamide group experienced disease recurrence, compared with 21% of patients in the oral cyclophosphamide group.

Thus, although cyclophosphamide-based regimens have significantly modified disease mortality in patients with ANCA-associated vasculitis, disease relapse remains common and the burden of glucocorticoid therapy remains high. Glucocorticoid toxicity was not systematically measured before and during the 2000s because formal means of measurement were not available and larger toxicity concerns focused on the use of cyclophosphamide. The current choice of cyclophosphamide as the preferred remission induction agent involves weighing the pros and cons of both routes of administration, but rituximab is increasingly favored over cyclophosphamide. If cyclophosphamide is used at all, it should be used only in short-term (e.g., 3 months) regimens, whereas the long-term regimen (up to 10 pulses) used in the CYCLOPS trial is not recommended due to toxicity issues (e.g., malignancy), Regardless of the route of administration used.

Rituximab-based regimen

The successful use of rituximab, a chimeric monoclonal antibody targeting CD20+ cells, in the treatment of ANCA-associated vasculitis was first reported in 2001. In the RAVE trial, a regimen of rituximab plus glucocorticoids was compared with a regimen of daily oral cyclophosphamide plus glucocorticoids to induce remission to show that rituximab-based regimens were not inferior. The RAVE protocol stipulates that patients' combined prednisone treatment should be gradually tapered to discontinuation for more than 5.5 months. Sixty-four percent of the rituximab group and 53% of the cyclophosphamide (induction) and azathioprine (maintenance) groups entered remission without the use of glucocorticoids, the primary endpoint. In addition, the rituximab group was not inferior to the cyclophosphamide and azathioprine groups in inducing remission (p<0.001), but the advantage was not statistically significant (p=0.09). In patients with PR3 ANCA-associated vasculitis, rituximab was superior in inducing remission and had a higher rate of disease relapse, a finding that has been consistently observed across multiple studies.

Cumulative glucocorticoid exposure during the 18-month follow-up period was not statistically different between the two groups (4.6 g exposure in the rituximab group and 5.1 g exposure in the cyclophosphamide group), corresponding to a mean daily dose of 8.4 mg, respectively. and 9.3 mg, still a huge load. Patients in the RAVE trial did not take rituximab (or rituximab placebo) again at 6 months, and disease recurrence was common through the 18-month trial. Eighteen months after the start of treatment, 39% of the rituximab group and 33% of the cyclophosphamide group had sustained remission, so a single course of rituximab plus corticosteroids is not sufficient to maintain long-term remission in most patients.

In patients with MPO-ANCA-associated vasculitis and preserved renal function, the LoVAS (2021 LoVAS Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis a randomized clinical trial..pdf) trial Rituximab plus low-dose glucocorticoid regimens were shown to induce remission rates similar to standard-dose glucocorticoid regimens (71% vs. 69%), and the low-dose regimen was associated with fewer serious infections: 5 vs. 13. Over 2 weeks, patients in the standard-dose glucocorticoid regimen received 4.2 g of glucocorticoids, and patients in the low-dose group received 1.3 g of glucocorticoids, corresponding to average daily doses of 22.8 mg and 7.2 mg, respectively.

Trial data on the efficacy of rituximab in patients with serum creatinine greater than 352 µmol/L (4 mg/dL) remain sparse, primarily because the RAVE Data and Safety Monitoring Committee requested this exclusion criterion rather than because there is evidence that Rituximab is not effective in this situation. However, some clinicians recommend combining rituximab with two pulses of cyclophosphamide in this setting as a strategy to help patients enter remission. This approach has not been subjected to randomized, double-blind trials, and there are concerns that this regimen may increase the incidence of infectious adverse events.

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.