Stress/cortisol/aldosterone cause kidney disease; pregnenolone/progesterone treat it
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The condition known as chronic kidney disease (CKD) is one of the most common long-term co-morbidity of diabetes/obesity. It is estimated that the majority of people with diabetes/obesity will develop some stage of CKD throughout their lives. The treatment options for CKD are virtually nill and rely on trying to reverse the underlying cause (diabetes/obesity) and perform dialysis or kidney transplants for the advanced cases. That being said, it looks like over the last couple of years, pharma companies have quietly been developing actual treatments for the condition, and the mechanism of action behind it is surprisingly simple. Namely, blocking the aldosterone (mineralocorticoid) receptors (MR). These recent drug approvals are a great development for several reasons. One, people now have an actual curative treatment available for CKD. Two, it immediately exposes the fraud behind the public health push for salt restriction since restricting salt raises aldosterone, and the latter is know proven to be a major cause of kidney failure. Three, it exposes the dangers of glucocorticoid usage/administration since in the absence of hyperaldosteronism (which is rare, unless one severely restricts salt intake) glucocorticoids (endogenous or given as drugs) are the primary activators of the MR. That’s right, while most people think of glucocorticoids as activators of glucocorticoid receptor (GR) only, they also activate the MR and this is what causes the well-known puffiness/edema in people with Cushing syndrome/disease or in patients treated with glucocorticoids. Of course, that also immediately exposes stress being a major cause of CKD as well, due to its effects on baseline cortisol levels. In any event, the drug below is one of the most recently approved MR antagonists as a treatment of CKD.
https://en.wikipedia.org/wiki/Finerenone
Now, like any pharma drug, the one above has a long list of undesirable (even serious) side effects. The good news is that there are cheap and widely available OTC remedies that can do the same as the pharma drug, with few known side effects. Namely, pregnenolone and progesterone are potent MR antagonists, and based on their pharmacological profile in regards to MR they likely provide benefit even in physiological doses. Come to think it, their decline with aging may explain to a great degree the positive association of CKD with age. Truly the youthful steroids, as Peat called them many times!
https://doi.org/10.1111/j.0954-6820.1960.tb06642.x
https://doi.org/10.1016/j.watres.2012.01.013
“…Highlights ► Steroid receptor profiling of STPs extracts using in vitro steroid receptor bioassays. ► Presence of agonist ER and AR, and antagonist GR, PR and MR activities in samples. ► Analysis of the STPs activities due to human steroids. ► AR, anti-GR and PR activities were not due to known human androgens. ► The steroid precursor pregnenolone is a potent anti-mineralocorticoid.”
“…Interestingly, using LC MS/MS (Liquid chromatography coupled to tandem mass spectrometry), we detected the presence of pregnenolone at high concentrations in the S2 and S4 samples. Using our bioluminescent reporter cells, pregnenolone was identified as a potent MR antagonist with a faint antagonist activity on PR and AR (Fig. 4B and Table 4 for the IC50) and a weak agonist activity on ERa (Fig. S3). Chemical analysis indicated that pregnenolone significantly contributed to the Bio-Spiro-Eqs (54.9 and 7.3% see Table 3). Altogether, these results identify pregnenolone as a novel EDCs acting as an important contributor to the detected antimineralocorticoid activity.”
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@haidut Love how you end your research report summaries with "...the good news is..." Also happy to see more posts from you in this forum!
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@haidut Thanks so much for posting this here. Great information!
I stayed at friends house the last couple of days for an event.
A no salt; no sugar; no dairy home.
I stopped at a bagel cafe on my way out of town and ordered a salt bagel. The waitress burst out laughing when she found me licking the big salt chunks on it with my eyes closed.
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This is so hard for me to understand. Especially when the language revolves around the idea of receptors. Once I get into that world, it just seems like an expert, not necessarily referring to you, is explaining to me some arcane terms in quantum physics.
I could be wrong here, but isn't the idea of receptors something that came off the mechanical model based on a Cartesian model that is at odds with the concept of a life force or field model that sees life than more than just something that can be reduced to a mechanical model?
What I can relate to in concept is our organs, and the kidneys being just one of them, as being a collection of tissues. Tissues are composed of cells, and cells that are healthy are governed by a balance. When there is balance, there is an abundance of well-directed energy that keeps cells and tissues and organs functional with a minimum of stress. With stress at minimal levels, the organ does not have to adapt to stresses that create conditions for organs to calcify and to develop fibrosis. And when the kidneys do not undergo calcification and fibrosis, it stays very functional.
As when it is supplied with necessary inputs such as oxygen and sugar, and it makes good use of them by having an environment that is supportive of productive and beneficial processes. An environment free of toxins, with microbes always present that are not harmful but commensal that is free from infection, and an optimal acid-base balance that allows each cell in the organ the regulation of calcium ingress and egress, with potassium doing its role in regulating calcium entry in the cell (that can only be achieved with having the pH levels that only good sugar-based mitochondrial metabolism can unfailingly provide with an abundance of CO2 production) and with the calcium being spirited out of the cell as it pairs with CO2 as bicarbonate to keep internal calcification from developing.
I like this kind of explanation nor only because it addresses my need as a child in me to satisfy what is the cause of an effect. As I can understand it better and I can apply it in other situations.
But I find it hard to understand aldosterone in how it acts as its presence has never been explained without me saying "oh I am not worthy." and I better move on and leave it to the experts.
The kidneys and how it get so sick that there is CKD is such a mystery to us all.
And we end up using some formula called the eGFR in it's various versions to determine how much deep into CKD we are from stage 1 to 5. Relying on a formula that is so simplistic involving only the input of creatinine, age, sex, and race to determine kidney health. In reality, eGFR means "estimated," and this estimate is so wide in its variance to render it practically worthless for diagnosis, but still doctors forget to treat it as an estimate, and see it as the gold standard in the absence of something better. Just one way the practice of medicine is more an art than a science, and as an art competes with economics for distinction in the Nobel hall of infamy, only bested by the Peace Prize with its laureate, Barack Obama.
Yes, the use of pregnenolone and progesterone is good and I have no objection to their use. But in the context that these steroids and hormones are already part of the cast of actors in a body running on optimal sugar metabolism, wouldn't they be redundant in a healthy individual? And shouldn't they be seen as temporary crutches to use while the long term direction is to guide the patient towards being metabolically independent from the use of progesterone and pregnenolone?
