Stress/cortisol/aldosterone cause kidney disease; pregnenolone/progesterone treat it

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.

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!

“…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.”

Author: haidut