Interesting for colleagues: Because of a patient, I researched the background of IgA nephropathy and found some things that could modulate the course of the kidney disease.
IgA1 nephropathy
IgA nephropathy is a form of glomerulonephritis characterized by deposits of immunoglobulin A (IgA) in the glomeruli of the kidneys. This is the most common form of primary glomerulonephritis worldwide.
Pathophysiology of IgA1 nephropathy
Pathophysiology:
IgA production: Abnormal IgA (mainly IgA1) is produced in increased amounts. This IgA often has abnormal glycosylation, resulting in reduced clearance and increased formation of immune complexes.
Immune complex deposition: These abnormal IgA1 molecules form immune complexes that are deposited in the mesangial areas of the glomeruli.
Inflammatory response: The deposition leads to activation of the mesangium, resulting in proliferation of mesangial cells and increased production of matrix and proinflammatory cytokines such as TGF-β, IL-6 and MCP-1.
Damage to renal structure: The inflammatory response leads to damage to renal structure, which can progressively lead to fibrosis, sclerosis and eventually renal failure.
The exact causes and mechanisms that The causes that lead to abnormal IgA production and glycosylation are not yet fully understood, but genetic predispositions, environmental factors and possibly infections play a role in the pathogenesis of the disease.
–> I actually found deeper causes here below
The abnormal IgA1 associated with IgA nephropathy is produced primarily in the mucous membranes of the respiratory and gastrointestinal tracts. The mucosa-associated lymphoid tissues (MALT) of these areas are major production sites for IgA, including the abnormally glycosylated IgA1 that plays a role in this disease.
Lymphocytes in these tissues produce IgA in response to local antigens or microbial pathogens, and dysregulation in this process can lead to the production of pathogenic IgA1, which contributes to the development of IgA nephropathy.
The production of IgA1, particularly the abnormal form involved in IgA nephropathy, is influenced by several factors:
Genetic factors: Genetic predisposition plays a crucial role in IgA nephropathy. Various genes regulating the immune system and inflammatory responses are involved. In particular, variations in the genes responsible for glycosylation of IgA1 can lead to abnormal glycosylation.
Immune response to infections: Acute or chronic infections, particularly of the respiratory or gastrointestinal tract, can stimulate increased IgA1 production as an immune response. The abnormal glycosylation of IgA1 could be a defective response to these infections.
Environmental factors: Environmental factors and diet can also affect IgA1 production. Studies suggest that certain dietary components or environmental toxins could affect the immune response and the production of IgA.
Inflammatory conditions: Chronic inflammation, even independent of acute infections, can trigger hyperproduction of IgA1. The chronic inflammatory milieu may support a dysregulated immune response.
These factors may act synergistically to promote the production of pathologically relevant IgA1, which plays a key role in the pathogenesis of IgA nephropathy.
current conventional medical therapies
local corticoid therapywith e.g. budenoside – comparable to Crohn’s disease or ulcerative colitis – this reduces IgA production in the intestine
Sparsentan is a novel drug candidate that acts as both an angiotensin II receptor blocker (ARB) and an endothelin receptor antagonist (ERA). These dual properties enable sparsentan to simultaneously block two important signaling pathways involved in the development and progression of kidney disease.
Details about Sparsentan
Mechanism of Sparsentan
Angiotensin II receptor blockade: Sparsentan blocks the angiotensin II type 1 receptor (AT1), thereby blocking the effects of angiotensin II, a potent vasoconstrictor and stimulator ofr aldosterone secretion, are inhibited. This leads to a reduction in blood pressure and a reduction in kidney inflammation and fibrosis.
Endothelin receptor antagonism: By blocking the endothelin receptor type A (ETA), the effects of endothelin-1, another powerful vasoconstrictor that contributes to the pathophysiology of kidney disease, are reduced.
Applications:
Sparsentan is currently being investigated in clinical trials, mainly in the context of diseases such as IgA nephropathy and focal segmental glomerulosclerosis (FSGS). These studies aim to evaluate the efficacy and safety of sparsentan in the treatment of these diseases, particularly in terms of proteinuria reduction and slowing the progression of kidney disease.
Research in Pubmed
Toll-like receptors – the carriers of the “innate immune system”
The “sick” immunoglobulin IgA1 is controlled and monitored via Toll-like receptors
Vitamin D controls this part of the immune system
I first got to know the TLR receptors during my extensive research into the Coimbra Protocol.
TOLL LIKE RECEPTORS (= TLR) are under the influence of the VDR (= vitamin D receptor). Disturbances of the VDR always lead to disturbances in the TLR function and thus ultimately to immune dysregulations including autoimmune diseases
two slides from my extensive VitD receptor lecture
VDR and TLR disorders – mostly genetic and easily treatable with COIMBRA
We have had great success with the COIMBRA protocol for autoimmune diseases and can demonstrate this in studies.
The vitamin D receptor controls the TLR genes and thus indirectly also the IgA1 nephropathy
16,000 studies with VitD and TLR9
11,000 studies with VitD and TLR7
1,400 studies with VitD and IgA1 nephropathy
In addition, there is a direct disruption of VitD metabolism in the kidneys of patients with IgA1 nephropathy
which leads to a significant reduction in the effective calcitriol and increased degradation
Interleukin-11 – new star in the anti-aging sky
for me a completely new pro-inflammatory cytokine, the reduction of which in the case of kidney damage led to a complete restoration of the kidney
by eliminating this cytokine interleukin 11, the test animals can live 20-25% longer!
could this actually help with IgA nephropathy?
Interleukin-11 also disrupts the kidneys in IgA nephropathy
Of course I found something to reduce interleukin-11, it also tested really well on patients, but I won’t reveal that in this article, I’ll be writing another article about IL-11 soon
Fish oil capsules are unfortunately rather bad
good thing I always check everything in Pubmed – the Omega-6 oils were neutral, the Omega-3 oils worsened the kidney values!!!
From the latest research by Dr Sabine Hazan we know that bifidus is extremely important because the blood is cleaned of inflammatory cytokines via the intestines with the help of bifidus
In any case, our Hazan – bifidus – treatment worked really well on the patient!
Of course, he was vaccinated with mRNA and from Sabine Hazan’s research we know that this causes the bifidus to disappear PERMANENTLY because the S protein acts like a bacteriophage against bifidus behaves.
With a “mild Coimbra protocol” one can expect to have a positive influence on the IgA1 nephropathy.
Measures to reduce interleukin 11 and IL-6 are certainly helpful.
Inflammatory cytokines are massively reduced with bifidus.
I will report on the further course of therapy for this patient!
(c) Image: Dalle via GPT
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