The Pathological Classification Of IgAN Has Been Updated. Patients With These Two Subtypes Of S1 Can Try Glucocorticoids.
Apr 24, 2024
Renal biopsy is the gold standard for the diagnosis of immunoglobulin A nephropathy (IgAN). Because it can help doctors better diagnose and evaluate the condition of IgAN patients. A series of studies found that focal segmental glomerulosclerosis (FSGS), also known as S1 type, was seen in 70% of patients with IgAN. Patients with IgAN with S1 features are associated with higher proteinuria levels at biopsy, more rapid loss of renal function, poorer renal survival, and may even have a poorer response to medications.
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Basic pathological research shows that the occurrence of FSGS may be related to three mechanisms, inflammation, capillary necrosis, and podocyte damage/hypertrophy. However, in the past, FSGS caused by the above three mechanisms were considered to be IgAN S1 type and were not subdivided into (S1). So, are the effects of these three mechanisms on IgAN and renal function consistent?
Recently, Kidney International announced the results of the VALIGA study. The study has two important conclusions:
① The S1 classification should be further divided into 3 subtypes.
② Patients with S1 IgAN who have podocyte hypertrophy or whose glomeruli only show adhesion lesions respond better to glucocorticoids.
Research design
VALIGA is a retrospective cohort study of patients diagnosed with primary IgA nephropathy from 55 medical centers in Europe and did not measure baseline proteinuria or estimated glomerular filtration rate (eGFR) levels. limit. All patients were followed for at least 1 year unless end-stage renal disease (ESKD) progressed during this period.
The exclusion criteria for this study were patients secondary to other diseases and systemic diseases (such as systemic lupus erythematosus, diabetes, Henoch-Schönlein purpura), and patients with <8 glomeruli in renal biopsy samples.
In addition to recording the patient's eGFR, proteinuria, and blood pressure, this study also recorded the patient's medication use, such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (collectively referred to as RASB), glucocorticoids, or other immunosuppressants (such as cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors).
The primary endpoint of the study is the renal composite endpoint, defined as ESKD (eGFR ≤ 15ml/min/1.73㎡, receiving dialysis or kidney transplantation) or a decrease in eGFR of more than 50% compared with baseline.
The S1 classification is subdivided into three subtypes based on renal biopsy, non-specific lesions (NOS), adhesive lesions of NOS lesions (Adh), and FSGS lesions of podocyte hypertrophy (PH), which are simplified in this study to NOS lesions, adhesive lesions and PH lesions.
Chi-square automated interaction test (CHAID) was used to evaluate the relationship between S1 subtype and proteinuria and the primary endpoint.
Research result
A total of 1147 patients were enrolled, 73% of whom were male. At the time of the initial renal biopsy, the average patient age was 36±16 years old, eGFR was 73±30ml/min/1.73㎡, proteinuria was 1.3 (0.6~2.6)g/d, and mean arterial pressure (MAP) was 98± 13mmHg. 10% of patients received immunosuppressants. The median follow-up time was 4.7 (2.4-7.9) years. Sixteen percent of patients met the primary endpoint, and 12% progressed to ESKD.
1 Kidney biopsy results
The average number of glomeruli in renal biopsy was 16 (12-23), of which M1, E1, and S1 lesions accounted for 28%, 11%, and 69% respectively. The occurrence rates of crescentic lesions C1 and C2 were 9% and 2%, respectively.
2 Lesions and proteinuria
CHAID analysis found that there were significant differences in proteinuria among patients regardless of the presence of NOS lesions (+/-), PH lesions, or Adh lesions. Further analysis found that NOS- and Adh-patients were significantly associated with better renal prognosis. Adh+ and PH+ patients were associated with worse renal prognosis.
3 Effect of drug treatment on S1 subgroup
We conducted a propensity study to match the risk of disease progression in patients who received CS and RASB versus those who received RASB alone. The results found that risk factors for disease progression were similar in patients receiving CS and RASB versus RASB alone. In patients with S1 IgAN who had podocyte hypertrophy or whose glomeruli showed only adhesive lesions, renal survival was much higher with CS and RASB than in patients treated with RASB alone, with a time-dependent risk of 0.30 (95% CI, 0.14 ~0.68; P = 0.004;).
research discussion
IgAN pathological classification can predict patient prognosis and guide doctors in choosing the correct clinical intervention method. About 70% of IgAN patients can be classified as S1 type, which is one of the most common pathological classifications of IgAN. Consistent with previous studies, 69% of IgAN patients in this study had S1 classification. However, the S1 subtype is associated with injuries of multiple etiologies and pathways.
In addition to being associated with viral infection, drugs, ischemia, podocyte damage, genetic abnormalities, or racial susceptibility, FSGS (S1) is also associated with elevated levels of certain soluble factors. Just as secondary and primary IgAN may have different treatment priorities, different causes or injury patterns may reflect differences in the effectiveness of different intervention models in treating patients. Therefore, many scholars believe that S1 may be classified as Then subdivided into some subtypes.
Ei. Karoui et al. used the Columbia classification system of FSGS to subclassify S1 lesions in the IgAN cohort but modified the NOS subtype to avoid segmental sclerosis caused by inflammatory scars. A total of 128 IgAN patients were included, including 11 cases with collapsing type, 27 cases with cellular type, 7 cases with portal/periportal type, 6 cases with apical type, and 52 cases with non-specific FSGS. Both the collapsing and cellular forms have a particularly poor prognosis, with most patients progressing to end-stage disease, whereas the apical form is relatively better. However, in this study, the biopsy proportions of apical type, protein-absorbed droplet, and hyaline degeneration were only 3%, 4%, and 2% respectively, and the sample size was too small to draw valid conclusions. In order to make the subclassification clinically meaningful, it is possible that IgAN does not apply to the FSGS pathological classification system, that is, the Columbia classification.
At the suggestion of pathologists, we tried to use a new classification method and divided S1 into three subtypes: non-specific lesions (NOS), adhesive lesions of NOS lesions (Adh), and podocyte hypertrophy (PH) of FSGS lesions. The results It was found that this classification method can effectively stratify the risk and guide medication for patients with IgAN S1 pathological classification to a certain extent.
Of note, the majority (97%) of the patients in this study were Caucasian. Similar studies should be carried out in the Chinese population to verify the clinical significance of the S1 subtype.
This study believes that IgAN S1 pathological classification should be subtyped in the future, which can help doctors effectively risk stratify and guide medication for IgAN 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.
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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.
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.
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.
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.
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.
