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Minimal Change Disease: Is It Time for a Change In Treatment?

In a brief detour away from my cancer series, I felt the need to address a topic that has also hit me very close to home. Now, for the sake of anonymity I will not address whom it is affecting, but this is more an exercise in both educating myself and others about a rare disease, as there is not too much out there right now. Now, unfortunately, this is likely to fall upon deaf ears, but I assure you I care more deeply about this person than any doctor ever could and I can only pray that perhaps at least some of it will be considered.

Minimal change disease (MCD) is a kidney disorder which most often affects children and has an average incidence rate of between 0.23-15.8 out of every 100,000 children per year [1].

It normally presents with facial and other edema (excess fluid build up) and occasionally with respiratory issues, headache, irritability and fatigue [2].

The primary clinical signs are proteinuria (protein in the urine) and hypoalbuminemia (decreased albumin protein levels in the blood) [2, 3]. This decrease in albumin changes the osmotic pressure, which in turn causes sodium retention to maintain normal blood pressure, with edema as the result [2, 4].

While the cause is currently debated, an examination of the common signs and conventional treatments may help elucidate its etiology [5].

T-cell (T lymphocyte)-mediated inflammation, and subsequent damage to the glomerular epithelial cells (GEC), or podocytes, is thought to increase albumin permeability [5, 6, 7]. While the podocytes normally act as a filter for these proteins, when the integrity of this barrier becomes compromised, nephrotic (kidney) diseases can result [6, 7].

So what can instigate this immune dysregulation and inflammatory response?

There are a number of factors, but a primary mechanism is by way of increased expression of the CD80 transmembrane protein, induced by lipopolysaccharides (LPS) and/or other lipoproteins, which bind to the toll-like receptors (TLR) [8, 9, 10]. You may remember these from our discussion in Part 5 of my Cancer: An Odyssey series.

Other excitatory elements include viral infections, food and environmental allergies/sensitivities, other autoimmune conditions and even cancer, through the overexpression of various interleukin cytokines and the nuclear factor kappa B (NF-κB) pathway [11, 12, 13, 14].

Basically, something causes the immune system to get dysregulated and launch an overactive response against the podocytes; this is the textbook definition of an autoimmune disorder.

In fact, other autoimmune conditions can act in both the induction of minimal change disease and MCD may predispose individuals for other ones [11, 15, 16, 17].

So how is it treated?

The front-therapy for MCD currently consists of corticosteroids, particularly prednisone and dexamethasone, which have anti-inflammatory and immunosuppressive properties [18, 19]. Unfortunately, these drugs also induce one of the primary symptoms, sodium retention, and may actually cause facial edema, or moon face, one of the primary signs of MCD [3, 20, 21].

As someone who presented with this phenomenon during my childhood use of corticosteroids for asthma, before being treated by my father, I can assure you this is not fun and fellow children generally are not particularly forgiving.

Another common therapy is through the use of angiostenin-converting-enzyme (ACE) inhibitors to modulate blood pressure dysregulation and more direct immunosuppressants, such cyclophosphamide [22, 23].

More recently, rituximab, a monoclonal antibody, has been used as initial therapy, or in those resistant to steroids and immunosuppressants [7, 24, 25]. Rituximab effects the immune system by controlling the interaction between B-cells (B lymphocytes) and T cells [26, 27].

So basically, the core goal of the primary treatment modalities is to bring down inflammation and modulate the immune system.

Does this sound like anything else I have discussed recently?

Again, as I addressed in Part 5 of my Cancer: An Odyssey series, immune dysregulation presents in four distinct, but interrelated ways: under- or overreaction to internal or external stimuli.

In the case of an autoimmune condition, such as minimal change disease, an external stimulus precipitates an abnormal immune reaction wherein the body attacks itself.

So rather than try to simply suppress the immune system, would it not be more prudent to get it to properly regulate itself?

Intestinal permeability, or “leaky gut”, is a driving factor in bacterial translocation and subsequent circulation of LPS [28]. Given the established role of LPS-induced podocyte damage, maintaining intestinal barrier integrity is essential in minimal change disease [29].

Probiotics have demonstrated efficacy in gastrointestinal wall repair and immune regulation [30, 31, 32], as well as benefits as a therapy for nephrotic syndrome and kidney disease [29, 33, 34, 35].

Moreover, diets devoid of the gluten and casein proteins, found in wheat and dairy, respectively, have exhibited efficacy at improving childhood nephrotic disease and regulating the microbiome [36].

One other major issue of nephrotic syndrome in children is micronutrient deficiency, particularly in vitamins D and K, likely due to malabsorption issues related to the leaky gut [19, 29, 37]. In fact, vitamin D appears to play a therapeutic role in protecting the podocytes from the damage associated with MCD [19, 37].

So what should we do?

Long term use of corticosteroids and immunosuppressants will lead to a host of problems, including behavioral issues, increased susceptibility to infection and stunted growth [38, 39, 40, 41, 42, 43, 44]. All of these symptoms I can personally attest to from my own childhood experience with corticosteroids for my severe asthma. Now, while I concede that the goal of these therapies is short-term, most individuals with minimal change disease end up requiring them again at some point down the road.

Cliché or not, the definition of insanity is doing something over and over, yet expecting different results.

By focusing on gut health, we can allow the body to return to a normal immunoregulatory state.

Grass-fed gelatin and bone broth can help provide the necessary components to rebuild the epithelial cell walls of the intestines and the kidney. Whereas fermented foods and supplemental probiotics (ideally MegaSporeBiotic) can also help repair the lining, while also fostering a beneficial environment for healthy gut flora.

An autoimmune protocol based elimination diet excluding grbains, legumes, dairy, nuts, seeds and nightshades could also be beneficial in removing dietary triggers, as well as in allowing the gut lining to repair.

Adequate protein intake (between 1.5-2.5 g/kg) and potentially some moderate salt restriction would also be prudent [45].

Now, there is a thought experiment I have become quite fond of called “The Fireman's Paradox”. I initially heard Peter Attia discuss it at a conference many years ago in relation to cholesterol and heart disease. However, I have found the logical extension of the thought to be quite applicable to many other health challenges.

In the case of minimal change disease, it is not that we should not call the firemen in an emergency, but when an arsonist is on the loose, wouldn't it be more prudent to call the police as well?


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