The Immunosuppressive Treatment Regimen For LN Patients Should Be Adjusted Individually Based On Renal Biopsy And Clinical Indicators.

The goal of treatment in lupus nephritis (LN) is to slow disease activity to improve kidney and long-term patient outcomes. However, current treatment options cannot achieve complete clinical remission for most patients, and even after clinical remission, the recurrence and mortality rates of patients are still high. Therefore, most patients may need long-term immunosuppressive treatment. Some studies have found that LN patients are still using immunosuppressants 10 years after induction therapy. Some experts even pessimistically estimate that some LN patients will need lifelong immunosuppressive therapy. Inhibitors. On the other hand, long-term use of immunosuppressants is associated with infections, irreversible organ damage, and malignancy. Therefore, how to adjust immunosuppressants individually and accurately is a question worthy of concern to doctors.

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Recently, JASN released a joint recommendation from experts from many countries (the United States, Germany, Australia, the Netherlands, etc.). They believe that patients should undergo repeated renal biopsies during different periods of LN induction therapy to individually adjust the immunosuppressive medication regimen. This article is divided into two parts, namely the background and significance of the proposal, and the specific road map.

Background and sources of advice

Currently, immunosuppressant discontinuation or dose reduction in LN is based on complete and partial remission of LN, which is defined as improvement or stabilization of renal function and improvement of proteinuria. However, proteinuria is also a biomarker of immune responses, both acute and chronic. As LN treatment progresses, the patient's inflammation level decreases, which can lead to a decrease in proteinuria. However, if the nephron has suffered histological damage, it may also develop proteinuria or increase urinary protein levels in the future. And this could be misinterpreted as a relapse of the immune response.

A clinical study of repeated kidney biopsies tested this hypothesis and showed that the results of kidney biopsies (or kidney lesions) are variable. For example, cellular crescents, karyorrhexis, and fibrinoid necrosis tend to resolve rapidly during initial treatment, whereas intracapillary hyperplasia, hyaline deposition, and interstitial inflammation clear more slowly during ≥3 years of maintenance treatment. Glomerular immunoglobulin and complement abnormalities persist for more than 3 years, and complete regression of glomerular immunofluorescence usually lasts for more than 10 years. Despite aggressive immunosuppressive therapy, chronic kidney injury can occur early in the course of the disease. Therefore, consideration of whether to discontinue or reduce immunosuppressants should not be based solely on proteinuria levels but should be combined with other clinical and histological (e.g., renal biopsy) evidence.

Therefore, scholars conducted the WIN-Lupus study, which enrolled 96 patients with biopsy-proven LN, received immunosuppressive therapy for 2 to 3 years, and achieved complete or partial clinical remission (specifically defined as complete remission). : Normal or stable renal function, inactive urinary sediment, proteinuria <0.2g/d; Partial remission: normal or stable renal function; inactive urinary sediment, stable proteinuria, or urinary protein <0.5g/d). LN recurrence (biopsy-confirmed) occurred in 12.5% of patients receiving continued immunosuppressive therapy and in 27.3% of patients who discontinued immunosuppressive therapy, but this did not reach statistical significance.

It should be noted when interpreting the above data that clinical remission cannot be confirmed by biopsy, so it cannot be ruled out that some micro-inflammatory reactions or lesions still occur in the renal tissue. The LuFLA study showed a correlation between clinically undetectable histological activity and future LN recurrence. In the LuFLA study, 44 patients who had been on immunosuppressive therapy for at least 36 months and who had achieved clinical complete remission (proteinuria <0.5 g/d, inactive urine sediment, normal serum creatinine) for at least 12 months received a second dose Renal biopsy was performed, and immunosuppressive therapy was gradually discontinued. Over the next 2 years, LN recurred in 11 patients (25%), with a recurrence rate of 5.5 attacks per year. Among these 11 patients, 91% had high renal tissue activity scores. It is worth noting that all patients with a renal tissue activity score of more than 2 experienced LN recurrence. By multivariate analysis, the best model for predicting LN recurrence included lupus duration and residual intracapillary cellular proliferation in biopsy. Experts believe that intracapillary cell proliferation is one of the most difficult histological lesions of LN to alleviate.

Therefore, to help physicians determine whether patients with clinical and histological remission can discontinue immunologic agents. One cohort study found that among patients with complete histological response (renal tissue activity score of 0), only 9.2% of patients developed LN recurrence, with an incidence rate of only 1.5 attacks per year.

Based on the results of the above-mentioned studies, experts have developed a personalized immunosuppressant discontinuation path map, which can help doctors better guide patients to discontinue medication and reduce the patient's risk of LN recurrence.

For LN patients who have received induction therapy and supportive therapy for 12 months, if the patient achieves complete remission, immunosuppressive therapy should be continued, but for LN patients with partial remission, the proteinuria level needs to be determined. In patients with LN whose proteinuria does not improve further, repeat renal biopsy should be considered. Based on the renal biopsy results, it is judged whether the patient should continue to use immunosuppressive therapy or adjust the immunosuppressive therapy plan.

For LN patients who have received induction therapy for 36 to 42 months and whose clinical symptoms have subsided, they need to undergo another renal biopsy, and based on the renal tissue activity score of the renal biopsy, it is judged whether the patient should stop immunosuppressive therapy. For patients with a renal tissue activity score of 1 to 2, non-renal factors such as anti-ds-DNA antibodies and serum complement need to be considered before deciding whether to stop immunosuppressive therapy. For patients with persistently positive extrarenal lupus biomarkers, renal biopsy should be repeated every 24 months until the renal tissue activity score becomes 0 before stopping immunosuppressive therapy. If the patient has extrarenal disease/symptoms requiring immunosuppressive therapy, immunosuppressive therapy should be continued.

For LN patients aged 60 to 68 months, in addition to considering the renal tissue activity score, if the chronicity index is stable, stopping immunosuppressive therapy can also be considered, but extrarenal factors need to be considered, such as the performance of skin and other biomarkers.

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.

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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.

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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.