Diagnosis And Treatment Of ANCA-Associated VasculitisⅤ

Avacopan

Avacopan is a small-molecule drug that inhibits the C5a receptor (C5aR1). It was approved by the US Food and Drug Administration in 2021 as an adjuvant therapy to induce remission. In the ADVOCATE trial, patients received a mean daily glucocorticoid dose of 47 mg in the avacopan group and 52 mg in the prednisone group 2 weeks before randomization, with a maximum of 20 mg of prednisone per day at the time of randomization. Baseline prednisone therapy in the Avacopan group was tapered to discontinuation over 4 weeks, while glucocorticoid therapy in the control group was tapered to discontinuation over 20 weeks. Avacopan (or placebo) treatment continued through week 52. The primary endpoint was defined as remission and no glucocorticoid use during the first 4 weeks at two-time intervals (weeks 2G and 52). At 2 weeks, there was no significant difference in efficacy between the two groups, with 72% and 70% reaching the primary endpoint respectively; at 52 weeks, the response rates of the two groups were 66% and 55% respectively (p=0.007). In the ADVOCATE trial, rituximab was not re-administered at 26 weeks, and if rituximab, now recognized by health authorities as the standard of care was re-administered, the results at 52 weeks may be indistinguishable.

Click to Cistanche for kidney disease

In patients with kidney disease, estimated glomerular filtration rate (eGFR) increased by an average of 7.3 mL/min/1.73 m² (avacopan group) and 4.1 mL/min/1.73 m² (prednisone group) at week 52 ( p=0.029), 50 patients with baseline eGFR less than or equal to 20 mL/min/1·73m² (27 patients were randomized into avacopan group and 23 prednisone group) found that the average increase in eGFR was 16.1 mL/min /1·73m² (avacopan) and 7.7 mL/min/1·73m² (prednisone), further emphasizing the potential of avacopan to help improve renal function recovery.

After 52 weeks, patients in the avacopan group received a total dose of 1.7 g of glucocorticoids and 3.8 g in the prednisone group, equivalent to average daily doses of 5 mg and 13 mg, respectively. Therefore, avacopan is more likely to be used in the treatment of severe renal disease, and in this setting, it is critical to minimize glucocorticoid exposure.

plasma exchange

The role of plasma exchange in the treatment of ANCA-associated vasculitis remains controversial. The results of the MEPEX (2007 MEPEX Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis .pdf) published in 2007 showed that compared with the regimen using intravenous pulses of methylprednisolone, the addition of plasma Replacement reduces the risk of end-stage renal disease at 12 months. However, first-year mortality was higher in both groups: 27% in the plasmapheresis group and 24% in the intravenous methylprednisolone group. These high mortality rates are more due to infectious complications than to characteristics of active disease or vasculitic comorbidities.

The randomized (but not blinded) PEXIVAS study (2020 PEXIVAS Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.pdf) included 286 patients with PR3 ANCA-associated vasculitis and 418 patients with MPO ANCA-associated vasculitis, and its primary endpoint was final End stage renal disease or death. Both outcomes are complications of ANCA-associated vasculitis, which, if they do occur, usually do not occur for at least several years. In contrast, the positive effects of plasma exchange in severe pulmonary and renal syndrome usually occur within the first few weeks after initiation of treatment. Therefore, PEXIVAS is unlikely to show important and durable benefits of plasma exchange, as standard treatments for this disease manifestation already have substantial efficacy. Furthermore, the concept that plasma exchange, added to standard care only at the start of treatment, would significantly change results years later is unlikely to be shown in trials.

Twenty-eight percent of patients in the plasma exchange group and 31% of patients in the control group achieved the primary endpoint of end-stage renal disease or death during a mean follow-up of 2.9 years (p=0.27). These results have not led many clinicians to change their views on the role of plasma exchange, and physicians who did not support plasma exchange before the trial cited it as evidence that the treatment was not worthwhile. Clinicians who still believe in the potential value of plasma exchange assert that the trials are inappropriately designed to address the setting in which plasma exchange is most appropriate, and so they continue to use plasma exchange. Therefore, the use of plasmapheresis remains a center-based decision. If used at all, it probably should be used early in the treatment of critically ill patients and should be used in experienced settings that are adept at reducing the significant risk of infection.

A meta-analysis that included trial data collected over 40 years reported that patients with serum creatinine concentrations greater than or equal to 3.4 mg/dL were less likely to develop end-stage renal disease within 1 year when plasma exchange was added to standard care. Plasma exchange-related infections were also confirmed.

Methotrexate

Methotrexate is used to induce remission in patients for whom other treatments are contraindicated, unwilling, poorly tolerated, or unavailable. From 1992 to 2010, it was frequently used in patients with localized granulomatosis with polyangiitis (panel), but its use has declined significantly since rituximab was approved for remission induction in 2011. Methotrexate appears to be effective in inducing remission when given in combination with glucocorticoids but has never been tested against glucocorticoid-alone treatment in clinical trials with glucocorticoids. The likelihood of disease flare after discontinuation of prednisone appears to be high. However, in certain clinical situations (e.g., the height of the COVID-19 pandemic), methotrexate may be a useful part of a remission induction regimen in patients without severe ANCA-associated vasculitis. In patients with chronic kidney disease, the drug dose should be reduced and no drug dose should be given in patients with an eGFR less than or equal to 30 mL/min/1·73m², as the risk of methotrexate toxicity is increased in this setting.

In summary, over the past 20 years, the trend in remission induction strategies for ANCA-associated vasculitis has shifted from reliance on cyclophosphamide to rituximab in patients with systemic disease. Shorter courses of glucocorticoids and regimens aimed at complete reduction and reduction of glucocorticoids are also emphasized, although clinicians may still be overly reliant on these regimens in practice. Avacopan is an important adjunct to the induction of remission and can significantly shorten the duration of glucocorticoid exposure. All patients undergoing induction of remission should use trimethoprim + sulfamethoxazole (TMP + SMX) or other appropriate antibiotic regimens for prophylaxis during induction of remission, as TMP + SMX is not only effective in preventing Pneumocystis jiroveci infection Effective and also effective in reducing the incidence of bacterial infections in treated patients with ANCA-associated vasculitis.

Maintenance of remission

Since 2021, guidelines and recommendations issued by the American College of Rheumatology/Vasculitis Foundation (ACR/VF) and the European League of Rheumatology Associations (EULAR) recommend the use of rituximab as a first-line agent to maintain remission. The MainRitsan1 trial randomized patients newly diagnosed or returning to rituximab or azathioprine after induction therapy with cyclophosphamide. At 28 months of follow-up, 5% (rituximab) and 29% (azathioprine) of patients experienced severe relapse, and the safety profiles of the two treatment regimens were comparable.

The RITAZAREM trial randomly divided patients who relapsed after induction therapy with rituximab into two groups. One group continued to take rituximab, and the other group switched to azathioprine to maintain remission. During a follow-up period of at least 3 months, disease recurrence was recorded in 15% of patients (remaining) and 38% of patients (switched), and fewer serious adverse effects were observed in the remaining group using rituximab event.

If rituximab is contraindicated in the patient, azathioprine remains a second-line approach to maintaining remission. Azathioprine also plays a central role in the treatment of ANCA-associated vasculitis in pregnancy because the drug is considered safe for pregnant women. The RIME trial compared azathioprine plus corticosteroids for 48 months versus discontinuation after 24 months. Overall relapses and major disease relapses were more frequent in the group receiving shorter courses of therapy, highlighting the efficacy of prolonged azathioprine plus glucocorticoids in maintaining remission.

In the MAINRITSAN2 trial, maintenance of rituximab at fixed intervals (every 6 months) was compared with tailored dosing based on changes in ANCA titers or reappearance of CD19+ B lymphocytes. During follow-up, the number of infusions was reduced to three in the customized treatment group and five in the fixed-interval group. Although patients in the customized group had a higher rate of disease recurrence at 17% compared with 10% in the fixed group, the difference was not statistically significant. Neither the ACR/VF nor EULAR recommendations support customized rituximab regimens, but clinical practice varies widely.

Additionally, the COVID-19 pandemic has also greatly impacted the frequency of rituximab retreatment, causing clinicians to become less stringent about retreating B-cell depletion. Decisions about whether or when to re-treat with B-cell depletion therapies are currently made based on the patient's perceived risk factors for disease onset and the potential impact of disease onset on the individual. For ANCA-associated vasculitis, no single response maintenance regimen is suitable for all patients.

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.