Article from Townsend Letter
Kidney Disease – How to Protect Your Kidneys As You Age and a Call for Functional Renal Medicine
by Devaki Lindsey Berkson, DC

One out of three Americans are at risk of kidney disease.[1] This equals tens of millions of people.

Often kidney disease is silent. Many who have it don’t know they have it. You might think an article on kidney disease doesn’t pertain to you because you don’t have symptoms and you are basically healthy. Or if you’re a practitioner, not a kidney doctor (a nephrologist)…why care? Typically, patients with kidney problems go to kidney doctors.

However, kidney health, as you will soon learn, “drives” heart health. Chronic kidney disease (CKD) is a heart attack (myocardial infarct) equivalent. Heart disease is the number one killer in both men and women.

Also, when patients with kidney disease see a renal specialist, they mainly get their progress tracked, or their decline monitored. They rarely get better or reverse the stage of their kidney disease. There are five stages of renal decline, from mild kidney damage in stage one, to kidney failure in stage five. Kidney failure is loss of 85% of normal kidney function. Dialysis can improve renal function only a bit above this 15% functionality number. It is not a superb fix, even though it is lifesaving and life-prolonging.

Doctors typically measure how well kidneys filter waste from the blood by the “estimated glomerular filtration rate” or eGFR. Estimated means it’s an equation based on a set of numbers. The eGFR is a number based on your blood test for creatinine, a waste product in your blood.

We want both healthy kidneys and heathy hearts. I think we should also strive to reverse renal disease, if possible, if we have it. Thus, this article.

Diabetes is one of the leading causes of kidney disease. Half of the people with chronic kidney disease[2] (CKD) also have diabetes. But not all. I had kidney disease for 16 years and am thin, athletic, and without blood sugar or diabetic issues.

People with kidney disease in the early stages (stages one through three) have very few “symptoms.” Kidney disease is one of the silent diseases (like cancer).

People with kidney disease are prone to excess levels of potassium in their blood.[3] When potassium builds up in the blood, it becomes dangerously toxic to many tissues. For example, too much potassium in the blood can cause heart block in the electrical conduction system of the heart and/or cardiac arrest, which is an abrupt loss of normal heart function.

As we age, renal filtering (or kidney function) starts to decline by 1% per year after the age of 40. If we have high blood pressure, this can also be harmful to the kidneys and can amplify this percentage of decline.

As kidney function falls—demonstrated by declining blood levels of eGFR (estimated glomerular filtration rate) and/or rising creatinine—potassium levels start to rise.

Increasing blood levels of potassium is a sign of worsening kidney disease. However, regulating blood potassium levels is complicated. Many foods we should eat plentifully, like fruits and veggies, are very high in potassium. Some important medications worsen potassium levels. This means that the treatment of kidney patients becomes a balancing act between diet, nutrients, and medications.

Everything in the body is all about Goldilocks. The body likes “just right.”  Levels of potassium that are either too low or too high are not healthy for anyone, especially for those with renal disease.[4] Ideally, potassium levels should be near mid-4 millimoles per liter (mmol/L) and not creep up to 5 mmol/L or higher, especially in someone with kidney disease.[5]

There are nuances of testing potassium levels in the blood. Many don’t realize that potassium goes up and down throughout the day. Potassium levels are higher after eating and lower with fasting. Therefore, in learning how your body and kidneys process potassium, it is best to use a fasting blood test.

The colon facilitates some excretion of potassium. In people with healthy kidney function, the colon helps rinse 10% of potassium out of the body that came in from food. In people with renal decline (chronic kidney disease or eGFR—estimated glomerular filtration rate— below 60), the colon can pick up some of the kidney slack and can excrete 30 to 35% of the potassium from what we eat. Thus, gut health intermingles with kidney health. If the colon isn’t up to this “back-up” renal task, more potassium can build up in the blood.

Why diabetics have more vulnerability to excess potassium levels is complicated. There are several possible reasons. Diabetic patients are at risk of elevated blood potassium after taking certain medications for long periods of time, such as RAS blockers—renin-angiotensin system

medications like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers(ARBs), or aldosterone receptor blockers—especially if not on diuretics at the same time. But long-term diuretics can contribute to the complexity mix, too. Excess protein going through the kidneys can damage renal tubules. Also, people with diabetic kidney disease may have several types of kidney disease at the same time such as renal tubular acidosis (4 RTA).

Nature is great, but she isn’t simple.

What else can elevate potassium levels in someone with lowering renal function? Potassium levels can rise due to too much fruit, other medications, NSAIDs, more veggies than a person’s body can handle, and high blood pressure. Sometimes it is elevated by a laboratory artifact (lab tests can sometimes be wrong), a blood sample can sit around too long, or if the blood comes out very forcefully—red cells can lyse, (break apart) liberating the higher gradient of potassium inside the cell into the plasma, thereby artificially elevating potassium. This can also lower glucose artificially due to longer time in contact with metabolizing cells. Sometimes we just need to repeat the test to see if it’s real.

Veggies and fruits are high in potassium. This is fine for someone with healthy kidney function, but potassium levels need to be monitored in someone with declining renal function. But as you will soon learn later in this article, I think this is not “root cause” but a manifestation of an ill kidney. It may be that nasty molecules are “banging” kidney tissue into worsening function, so that the potassium in healthy foods becomes elevated in the blood. It would be better to figure out why the kidneys can’t process the potassium rather than avoiding all these healing foods. But for now…

Prunes, for example, are often used by seniors to treat constipation. They are very high in potassium. Potatoes are sky high in potassium. Fruits and veggies are healthy for many people but may not be good for you if you have kidney disease and excess potassium in your bloodstream—until you take other stress off your kidney, which we will go into soon.

Blood Pressure and Blood Sugar Medications

Blood pressure and blood sugar medications can complicate blood potassium levels. Some blood pressure medications are called “renal sparing” in that they slow down the progression of kidney disease. But they have to be taken in sufficient dosages to produce these protective actions. However, studies have repeatedly shown that only one in five patients with established kidney disease are receiving ACE and ARBs in the correct dose that is renal protective.

But these meds also have a potential shadow side. Long-term use of ACE and ARB medications can increase potassium. So treatment of these patients is a balancing act. Remember It’s Complicated! the movie with Meryl Streep and Alec Baldwin?

To summarize, drugs that prevent progression of kidney disease may be being underutilized. But these same drugs may also worsen the issue by creating a need for other meds that lower potassium. In addition, diuretics, (especially hydrochlorothiazide and chlorthalidone), which may be helpful to kidney disease, may also rinse out critical nutrients that are protective co-factors for enzymes in the cardiovascular system or even elevate damaging molecules that worsen kidney (and heart disease) like TMAO (tri-methylamine-N-oxide).

Blood sugar issues can add complexities.  Inadequacies of glucose control and degrees of insulin resistance (HA1C in the 7-9 levels) all contribute to elevated potassium in the blood. In fact, people with insulin and blood sugar issues are at the highest risk of kidney and heart disease.

Keeping potassium, blood sugar, and blood pressure balanced, and all responding to meds without making things worse, is complicated. Allopathic medicine prescribes meds to protect the kidneys, but other meds may be needed to protect against the side effect of the first meds. In addition, even more meds may be necessary to keep blood levels of protein, sugar, and minerals like potassium in ideal ranges.

Treating kidney problems can become a whirling dervish. Give a med to track a specific problem. Give another med to fix the problem the first med worsened. But all this while, “root cause” of why the kidneys are slipping down a rabbit hole is not being looked for nor addressed.

Hormones

Hormones[6], [7], [8] have a role in kidney health Estrogen is exquisitely renal protective.[9]. [10]. [11], [12], [13], [14]  Normal levels of testosterone are also renal protective especially as we age,[15], [16] although extreme levels of excess testosterone can be renal stressful.[17] Body builders consuming high levels of protein (especially combined with testosterone supplementation) may be vulnerable to kidney damage.[18]

Kidney filtering begins to decline in our 40’s due to hormonal waning. Our sex steroid hormones have started to slowly decrease since our mid-twenties, but this decline becomes steeper in our fourth decade.

Hormone replacement in individualized optimal amounts may be helpful in both men and women to protect kidneys. However, sex steroid hormonal support is not enough once kidney disease is established.

Molecules of Mass Destruction

What I have come to realize is that there are specific molecules that “drive” kidney disease. When these molecules are elevated, they damage kidney tissue. They “bang” against kidney cells and are the real cause of why potassium levels elevate, protein leaks, and kidney function gets worse.

High potassium is not a cause of kidney disease; it is a result. But at the molecular level, what is causing the kidney disease besides age or bad luck?

Identifying and addressing “cause” gets better patient results. Once these dangerous molecules are isolated, they can be normalized or optimized through dietary and nutrient intervention—without meds and while avoiding the pharmaceutical dance of complexity caused by meds.

Often the stages of kidney disease reverse. No matter the age of the patient.

I refer to these molecules that in excess “drive” kidney disease (and heart disease) as  “the molecules of mass destruction.”[19] Testing and optimizing these molecules, I believe, holds tremendous clinical promise for other portals to improve renal health, regardless of the age of the patient or the stage of their decline.

My Story

I had a nephrectomy because of a renal tumor, secondary to a drug my mother was given when pregnant with me. I had perfect kidney function before the surgery.  I was at stage two and then stage three renal disease for 16 years following the surgery. My mother, along with millions of women from 1938 to 1971, were given this drug, diethylstilbestrol (DES), as a “prenatal vitamin” to make a normal pregnancy more normal or to stop bleeding and protect a “threatened” miscarriage. Many, not all, DES sons and daughters, including myself, had tumors and cancer because of this in-utero drug exposure.

I was the perfect patient:  ate mindfully, exercised, on individualized hormone replacement, saw my trusty (I thought) nephrologist for all that time. However, no matter how often I saw my kidney doctor or how healthily I lived, my kidney function kept declining.

I would continually plead with my doctor, “How can this be happening? I am your exemplary patient!” He would shake his head; he had no idea. “But come back next year. I really like talking to you so if you want to come in every six months, do.”  But he had no answers to my continual questions as to why this was happening and how to reverse it.

Then…three things happened.

First, I ended up starting a drug company with one of my original kidney doctors. (We had to stop being doctor/patient once we started working together, of course). This involved a drug for dialysis and diabetic patients. It was an amazing experience to have the opportunity to work alongside Dr. Jack Moncrief in his clinic and dialysis center. He’s a kidney rock star.

Dr. Moncrief co-invented the home unit of dialysis (CAPD), came up with the original idea of telemedicine, and successfully lobbied and personally got President Bush to sign the bill to legalize it. Dr. Moncrief had a catheter named after him, brought organ transplantation to Austin, Texas, and opened the first dialysis center in Austin. Dr. Jack was honored at Stony Brook University, New York, at a huge renal industry gala, as being one of seven kidney doctors that made nephrology “what it is today.”

I worked side by side with this visionary man for many years. Dr. Moncrief would always point out: “Kidney health drives heart health.”[20] Many heart docs don’t know this—or don’t practice as if they do.

Second, it just so happened that I met another iconic physician: Dr. Mark Houston. Dr. Houston is also a visionary doctor. He is a cardiologist with a specialty in hypertension and looking for “root causes” of cardiovascular disease.

Dr. Houston created the concept and genre of “functional cardiology.”  He developed and teaches the entire 24-hour module at A4M (Anti-Aging Certification Course and Residency for MDs, NPs and pharmacists). I also teach at A4M, in the gastroenterology module.  After teaching all day, we were having dinner one night. Dr. Houston discussed with me how he tests and teaches that specific molecules “drive” heart disease.

There are hundreds if not thousands of peer-reviewed research articles on these molecules, demonstrating how they initiate and propel, on the molecular level, plaque, stroke, and heart attacks.

Remembering what Dr. Moncrief said, I started to take a look at these same molecules with renal disease. I thought, maybe these are the molecules that “tie” kidney and heart disease together.

In exploring PubMed I found that there are thousands of articles that implicate these molecules, when in excess, as the “main driving force” behind why kidney disease starts in the first place, and why it isn’t responding to meds alone in the second place. This science explained why these molecules influence rising potassium levels, increases in uric acid, declining filtering function, and ultimately why all of this seems so impossible to turn around.

The third thing that happened was my testing these molecules on myself. This demonstrated that most of them, in my blood, were many-fold elevated. Taking nutrient and dietary actions to normalize their levels (back to Goldilocks “just right” middle ranges) helped me conquer my 16-year-long battle of stage two and three kidney disease, to achieve completely normal kidney functioning.  In 10 months!

Meet “The Molecules of Mass Destruction”

Trimethylamine-N-oxide[21], [22], [23], [24], [25], [26], [27], [28], [29], [30] (TMAO) is known to drive heart disease, but it also drives kidney disease. When it is elevated, it predicts increased renal complications. High TMAO blood levels often demonstrate a dysbiotic gut biome (more bad than good gut microbes) but can also be caused by an elevation of the liver enzyme that makes it (FMO3). This enzyme can be elevated by endocrine disruptors,[31], 32] especially in fetal exposure in the womb.  This can have life-long effects on offspring.

TMAO note: There is the phenomenon of the “TMAO Paradox” (coined by Berkson). Some studies found an elevated TMAO is linked to adverse cardiac and renal issues, and others have not. Also, TMAO blood levels can be elevated by what we have regarded historically as healthy foods, such as fish and fiber. If TMAO is so “bad” then why does eating good foods like fish, raise blood levels?  An Australian group of researchers[33] tackled this controversial sticky wicket over TMAO. They found that TMAO levels, in a rodent model, were in fact not linked to atherosclerosis itself. But in fact, it was linked to a deeper tissue dive. High TMAO was linked withatherosclerotic plaque instability. Thus, it’s linked to an increased risk of heart disease but at more nuanced levels. It may also be that TMAO is responsive to overall gut milieu and diversity. Researchers[34] found, in a cross-over feeding trial, that those with less biome diversity and more Firmicutes than Bacteroidetes genus, had much more elevated TMAO after consuming fish. And fascinatingly enough, fish oil[35] has been found to be one of the elements that helps reduce blood TMAO levels.

It may also be that TMAO is a “bad actor” for some, while a benign actor for others. Sort of like IOP, intraocular pressure of the optic nerve. In healthy persons, elevated IOP is not big deal. Their healthy optic fibers can take ups-and-downs of pressure swings and even highs. But in unhealthy optic nerves, elevated IOP drives fiber destruction and threatens visual acuity. So, it may be that elevated TMAO is a risk factor for those genetically or lifestyle-wise “set up” for sensitivities to it. Time will tell as the TMAO/health link is being looked at more and more. I hope to write an in-depth article on TMAO, real or red herring, to do a deeper look-see into this. But in clinical practice, people feel better when TMAO levels decline, when these people are ill with renal disease. I even had one patient with intractable anxiety that had it all go away, including intractable insomnia, when her TMAO levels normalized.

Galectin-3[36] is a cytokine that when elevated predicts kidney disease.[37] Galectin-3 has been observed in elevated levels in many DES offspring. It’s been linked to causing or driving kidney tumors in Syrian hamsters exposed to DES in-utero.[38], [39] I am a DES daughter, exposed to this DES drug in the womb, and one of the tumors I had was renal.

Transforming Growth Factor Beta1 (TGFB1) is elevated in diabetic kidney disease[40] and drives fibrosis in renal disease.[41] I discussed this molecule with many of the original DES researchers, since I worked at an environmental estrogen think tank (Center for Bioenvironmental Research) with many of these scientists. Dr. William Toscano (who left Tulane to become academic dean of the University of Minnesota School of Public Health) told me that they realized early on that many, if not all, DES offspring had elevated TGFB1, but they weren’t sure what to make of it. Science now clearly shows that excessive levels of TGFB1, as many functional/environmental doctors now also know, is quite immunosuppressive. It also “drives” all fibrosis and this is part of the worsening tissue changes in both kidney and heart disease.

Asymmetric dimethylarginine (ADMA)[42] inhibits nitric oxide synthases and, when elevated, extremely enhances oxidative stress on the kidneys and cardiovascular system. Increased plasma ADMA levels are strong and independent risk factors for chronic kidney disease as well as various cardiovascular diseases such as hypertension, coronary artery disease, atherosclerosis, diabetes, and heart failure. After kidney failure there are dramatic increases of systemic ADMA and L-NMMA. These are kidney-nasty molecules.

N-monomethyl l-arginine (L-NMMA) works similarly to ADMA and elevates while the kidneys are declining and then increases enormously after kidney failure.

Symmetric dimethylarginine (SDMA)[43]—both asymmetric and symmetric dimethylarginine—are very toxic, non-proteinogenic aminos, which are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases, especially kidney and heart.

Potassium and uric acid, of course, need to be tracked meticulously, and there are many nutritional interventions to correct these without having to severely limit certain foods, like vegetables.

Cystatin-C[44], [45] monitors renal inflammation more sensitively than eGFR and is a great way to see if the intervention we are using is working.

When I ran these kidney damaging molecules on myself, I was shocked to see “all” of them in dangerous elevated ranges. All the while, my nephrologist kept saying I was stable and there was nothing left to be done. Yet…

My mentors at Tulane, where the environmental estrogen think tank was, confirmed that many DES offspring are high in many of these molecules. It wasn’t a toxic gut that was elevating my TMAO; it was the DES in the womb that up-regulates the enzyme that makes it in the liver.

So Now What?

Even if the seed of my kidney issues in adulthood were sown inside the womb, what could I do to save my lonely solo kidney and protect my life?

I sleuthed the literature for how to lower or optimize each of these molecules. It took dietary changes and nutrient interventions. I had to be careful of how many nutrients I used and which ones, as many of these are processed through the kidney.  I had to be very careful how much magnesium and minerals to take in, how to keep the kidney alkaline throughout the day, as kidneys love alkaline, and how to turn the flow of the clinical river without making things worse.

I made a lot of changes, even though by all standards I already ate really well. I gave up animal products and ate almost no protein except veggies and beans for three months to give my lone kidney some breathing space.

In addition, I took specific nutrients that the peer review research suggested could normalize levels. For example, I used modified citrus pectin to bring down the galectin-3. My uric acid was extremely high, so I went on herbs, quercetin, and tart black cherry juice, as well as vitamin C, and gave up all animal products. For a while. I monitored my potassium and let this guide my veggie intake. And re-ran my labs. And, within 10 months…all were normal!

I hadn’t felt ill. But now that these “molecules of mass destruction” were back in Goldilocks ranges, I felt fantastic. You don’t know when you are feeling less and less until you feel better more and more.

Who discovered these molecules, and why don’t more doctors test and treat them?

The Cleveland Clinic discovered many of these molecules and how they drive the beat of kidney and heart disease. There are over 4,000 peer review articles on galectin-3 and 1700 articles on TMAO. But still they have not reached most clinical trenches.

The peer review articles on these molecules establish their influence and toxicity when in excess and illustrate how to normalize them through various interventions—dietary and nutrient intervention.

My kidney doctor had never heard of any of these molecules except, of course, uric acid and potassium. I worked in Tulsa, Oklahoma, in 2011 when cystatin C was first recommended by the American Nephrology Association over eGFR, and we ran this kidney test there for $15 a pop. When I tried to order this test in Austin, it costs almost $600. My kidney doctor wouldn’t run it as he said my insurance wouldn’t cover it due to the high cost. I asked if any kidney doctors in Austin run it. He responded without hesitation, “I doubt it.”

I wanted to hear why my kidney doctor didn’t know about any of these exotic molecules of mass destruction. I’ve been going to the same good guy for most of these 16 years and asked how it could be that he didn’t know about these.  Dr. Rodriguez shook his head, “My association doesn’t mention them, thus, I am not guided to use them.”

I let out a huge sigh of frustration, “You know, I have been coming to you for 16 years, giving my kidney health into your hands. It’s very upsetting that I have been asking all those years why I can’t turn this around. Have you ever gone home and sleuthed the science to see how this might be happening to me? You know I eat so well, work out daily, do everything right but just keep getting worse. Be honest now, have you ever gone home with me in mind and hit the books?”

“No,” he sighed, “we just don’t know why.”

Well, I am a DES daughter. As it turns out, DES exposure in a developing fetus causes lifelong elevations of many of these molecules, the very molecules that drive kidney disease. But that never came up in our office visits (nor with any other doctor, honestly).

Let’s take galectin-3, for example. When experimental animals are exposed to DES in the womb, they develop excessive levels of galectin-3, which promote the development of kidney tumors.[46]

My kidney doctor shook his head. “Look, why don’t you do what you are planning on doing and retest your function in so many months. If you drop to stage two from stage three, I’ll change the way I practice, and I will teach functional nephrology.”

That’s what he said.

I huffed, “You can’t teach functional medicine. You’d have to study it first! But if you see that I improve, why don’t you and I together form a functional nephrology module and train others?”

To Dr. Rodriguez’s credit, he agreed. And he only required I improve by only one stage. But when I ran my labs 10 months later, I had recovered to “completely normal function,” even with one kidney, for the first time in 16 years.

I have to go back and see what he says. Will he add testing these molecules to his practice? Will he and I team up to spread the “functional nephrology” word?

He’s a smart younger man. He and his wife have gone vegan. They are cleaning up their diet. Why didn’t he know, as a kidney specialist, how excessive levels of TMAO can damage the kidney and how vegetarian-type diets can dramatically and quickly lower this molecule of mass destruction? Yikes!

I have a young 11-year-old type-1 very brittle (hard to control) diabetic, with worsening renal issues and chronic blood and protein in his urine. He has been seen by his nephrologist, a urologist, and his family doctor. None of them understand why this is happening. They continue testing and find nothing to give a drug for. The boy keeps urinating blood and having pain. And, of course, his mother is going out of her mind with worry.

So, I encouraged his mother to ask his nephrologist to run these molecules of mass destruction. Stunningly, the nephrologist refused.  He said he didn’t know what these were or how to interpret them. The mother said I could work with him to show him what I have been finding out.

He simply refused to be a team player or to work with my office on this. Although his office had no answers, he was not willing to take a look at other possible causes and answers, despite the fact that there are thousands of peer review articles linking these molecules to kidney disease. That’s how so much of this stands today.

I got so angry; I could grind my teeth to powder. What is a renal patient to do besides watching their kidney function worsen?

Functional medicine tries to identify “root cause” issues that drive disease, such as these molecules driving kidney disease. But presently there are no functional medicine renal modules anywhere in the world.

I have been offering to start teaching modules and CME courses in this. So far, the main certification courses for functional medical practitioners have not agreed to my proposals. Many doctors are not interested in renal care, as it seems to be the “rabbit hole” of medicine where patients just get worse and that’s expected. And accepted.

Well-intentioned kidney doctors can’t do much other than give you meds, tell you to drink more water, and track your progress as you most likely continue to decline.

I am presently working part-time at the Naples’s Center for Functional Medicine. (I am not able to fully pull myself away from my “Keep Austin Weird Lifestyle” in Texas, yet.) I look forward to working with patients with renal decline, to help get them back to normal kidney health. No matter their age.

This article is a start.

Got declining kidney disease? Come see me in Florida.

Be well.

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    Author bio:

    Devaki Lindsey Berkson, DC, has been in practice in functional medicine, with an emphasis on nutrition, hormones, intimacy, and digestion, for decades. Dr. Berkson is professor for higher board certification programs for medical professionals to become functional practitioners, such as A4M and PCCA. Dr. Berkson was a scholar at a hormone think-tank at Tulane, published original research with the University of Texas Medical School at Houston, and is a research fellow with Health Sciences Collegium. Dr. Berkson has been asked to be on a panel for the symposium “Functional Medicine is Coming” to the entire hospital staff at Houston Memorial Hospital this summer in 2019. Dr. Berkson wrote the first gut, mind, nutrition book published by Wiley (Healthy Digestion the Natural Way) and one of the first books on hormone-altering-chemicals (Hormone Deception. Dr. Berkson’s newest book, Sexy Brain, presents the newest health issue (environmental castration) and how to protect our intimacy and brain. Dr. Berkson consults around the world with patients and their docs. She has a very popular podcast, Dr. Berkson’s Best Health Radio, along with Berkson Blog at DrLindseyBerkson.com.

    Consult your doctor before using any of the treatments mentioned in this article.

    Reprinted with permission from the June 2021 Townsend Letter, and Devaki Lindsey Berkson, DC

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