Clearing up Kidney Confusion: Part Deux
It’s funny how our mental state really affects how we write and what we are interested in. When I wrote the introduction to this piece I was just getting settled into our new place in Santa Fe, NM and was looking at over a month at home to work and write. Then a number of wacky events happened and I’ve been home about 7 days out of the last month and I’ve only made it about 70 pages into Kon-Tiki.
Now I’m home for 8 days and will then be gone for a project that will take me completely off the grid for nearly 3 weeks. No phone, email…nada. When I sat down to do this kidney piece it was with a mindset that I had a ton of time and could really sink my teeth into it. Now I’m time crunched and anxious that I will get it done at all! Up front here I’d like to thank Mat “The Kraken” Lalonde with his help on some literature for this piece. Any inaccuracies however are my own tomfoolery.
If I wanted to cut to the chase I could boil this whole thing down to the following:
1-Dietary protein DOES NOT CAUSE KIDNEY DAMAGE.
2-Chronically elevated BLOOD GLUCOSE levels DO cause kidney damage.
3-Dietary fructose REALLY causes kidney damage.
4-Many kidney issues have either a hyperinsulinemic characteristic, an autoimmune characteristic, and or a combination of autoimmunity or hyperinsulinism. A standard, low-ish carb paleo diet can fix most of these issues.
5-For serious kidney damage a low-protein, ketogenic diet can be remarkably therapeutic.
6-If you get kidney stones that are from oxalates, reduce your green veggie intake (spinach for example) and have other types of veggies.
7-If you get kidney stones that are from urate salts, you are likely NOT following a low-ish carb paleo diet, you likely have insulin resistance and your liver is not processing uric acid.
As much as I’d like to leave it at that I’d be asking folks to operate on faith, not facts, so we need to do a little more digging. First we’ll look at normal kidney function, some common renal pathologies, how one might go about fixing those pathologies, then a clinical note or two.
The kidneys control a remarkable number of biological parameters, at least in those critters with kidneys! This includes blood pressure, filtering and removal of various metabolic waste products, blood volume, red blood cell count, electrolytes, acid base balance…Guyton’s Textbook of Medical Physiology has nearly 200 pages devoted to renal function, and that is a bare-bones overview with little time spent on pathophysiology. The lions share of kidney function involves filtration of the blood via a counter current exchange process that biology makes use of not only in kidneys, but also in the distal portion of limbs. In the case of kidneys, the counter current process retains or excretes various dissolved items as needed. In the case of limbs it’s an efficient method of minimizing heat loss (this is a common feature of the feet of birds who spend time with their feet in cold water).
Renal function is generally measured by glomerular filtration rate (GFR), but other indices are helpful including blood urea nitrogen (BUN) and the presence or absence of the protein albumin in the urine. GFR, when properly interpreted or implemented, should tell us how much actual filtration is occurring in the kidneys. If we know the concentration of an item like creatinine (a by-product of creatine breakdown) in the plasma and in the urine, then we have a good idea of GFR. The problem with creatinine is folks with larger muscle mass, or who train hard can have seemingly elevated creatinine levels, which can make GFR appear to be low. This is why it’s smart to also consider BUN and albumin. If BUN is going up we know the kidneys are NOT doing an adequate job. We are after all, accumulating nitrogenous waste products in the BLOOD (blood urea nitrogen). Conversely, if we see elevated albumin in the URINE we know we likely have kidney damage…proteins that otherwise stay in the blood are getting pushed into the glomerular filtrate (urine). In situations such as blood sugar highs in diabetics we can see glucose in the urine as a coping mechanism to bring blood glucose levels down, but that situation is bad, bad business.
Here is a brief recap of that:
1-Increased Creatinine: May not mean much, NOT a bullet proof demonstration of GFR.
2-Increased BUN: Bad news. GFR may actually be low, we are accumulating toxic nitrogen breakdown products like a boat taking on water.
3-Increased urine albumin: No Bueno. The kidneys are damaged, protein that should stay in the vascular system is leaking into the urine.
4-Glucose in the urine: Five Alarm No Bueno. As we will see, diabetes and the peri-diabetic state is hell on the kidneys.
Before we get all pathological, let’s first consider the basic units of the filtration system in the kidney:
In the first photo we have the Glomerlus which is neighbored by the the Bowman’s Capsule. The glomerulus itself is comprised by the afferent blood supply (in) efferent blood supply (out) filtration surface (kinda like a coffee filter) and the beginning of the proximal tubule (the coffee pot). This is the first stage of filtration in which large amounts of the fluid portion of the blood are literally pushed through the glomerlus and accumulate in the proximal tubule. In the second photo we see not just the Bowman’s capsule and glomerlus, but the whole functional unit of the kidney, including the distal tubule, loops of Henle etc. If you notice this structure is wrapped in a vascular web and it is at this interface that we can create either a dilute or concentrated urine depending on if our hormonal system is actively transporting things like sodium into the filtrate, or reabsorbing sodium (or other solutes such are urea) back into circulation.
As we will see, kidney function can head south from a variety of causes, but we will also see how our modern diet and lifestyle can compound pathogenic factors that bode poorly if you are interested in dead sexy kidney function (DSKF).
I’m not going to look at impact injury or trauma per se, but just keep in mind much of what I’ll describe below applies to trauma for the simple fact it damages the structural elements of the nephron. When I was Thai boxing many years ago I took several very nasty knees to the low back…and had blood in the urine for several days as a consequence. Some motocross riders experience the same things simply from the jarring of landing jumps. Many of our modern activities are damn fun, but not the healthiest of things to do!
When we consider how delicate the nephron is it should not be surprising that damage to various elements can cause problems. The main modes of action we’ll consider are advanced glycation end products (AGE’s), inflammation, abnormal growth, autoimmunity and hormonal alterations affecting kidney function.
You’d need to be living on a desert island to not know about AGE’s and their potential to negatively affect health. As the name implies, glycation is a process whereby a sugar binds to a protein or lipid. Now, this can happen enzymatically in the case of glycoproteins and glycolipids (a nifty way to modify the structure of these molecules and subsequently their functionality…this is also a major feature of immune recognition) or non-enzymatically, which is what we will look at. Free glucose, can, will and does stick to various proteins and lipids in our bodies via this non-enzymatic process. This is not a good scenario, as it does change the FUNCTIONALITY of these affected structures. Fortunately, we have enzymes that work to undo these unscheduled glycation events, and things work pretty well if we keep food and lifestyle within certain tolerances. In the case of metabolic derangement we have chronically elevated blood glucose levels which drive AGE formation in a concentration dependant fashion: more glucose means more AGE’s, and this can reach a level that overwhelms the enzymes which work to undo the AGE’s. Then we have fructose. Fructose has several unfortunate characteristics:
1-It tends to be processed mainly by the liver, so it’s tough to get it out of circulation.
2-Fructose tends to alter liver function, contributing to insulin resistance.
3-Fructose is structurally more reactive than glucose. At any given concentration, we can expect fructose to produce more AGE’s relative to glucose.
4-Fructosse tends to be pro-inflammatory via actions on both the liver, and alterations in gut bacteria.
AGE’s are problematic for kidney function as they damage delicate structures such as the glomerlus, which can limit normal GFR. Damage to the distal portions of the nephron can alter reabsorption. The net result is that our ability to filter out toxic substances such as urea and or regulate normal fluid and electrolyte balance are dramatically altered.
As y’all know, inflammation is a normal process caused by elements of our immune system. Normally this protects us from bacteria, viruses, parasites and cancer, but abnormal amounts of inflammation can get us in hot water (urine?). This is an interesting paper which demonstrates fructose is problematic for kidney function and one of the modes of action is actually an increase in inflammation via increased monocyte chemoattractant protein-1 (MCP-1). Monocytes are part of the innate immune response which we now understand is at ground zero in metabolic derangement and overall systemic inflammation. Once one element of the immune system is on alert, things tend to spiral out of control. In this specific situation, monocytes attack elements of the nephron, causing damage and decreasing renal function. Which leads us to…
Autoimmunity is when the adaptive immune system (the wiley part of the immune system responsible for producing antibodies…essentially a remarkable type of information processing and “memory”) begins to attack the host. Well known forms of autoimmunity include rheumatoid arthritis, multiple sclerosis and lupus. Less well known autoimmune diseases that affect the kidneys include autoimmune glomerular nephritis, which is actually a form of systemic Lupus. If you have attended either my seminar or Mat “The Krakn” Lalonde’s seminar, you will know that autoimmunity appears to have features of intestinal permeability with specific autoimmunity being driven in large part by genetic factors. Not surprisingly, a little investigation into search terms such as “glomerular nephritis + gluten” or “glomerular nephritis + trans glutaminase” produces some VERY interesting returns. If you need a reminder about the role of transglutaminase in autoimmune disease, please read this review on celiac disease a model for autoimmunity.
Chronically elevated insulin levels appear to have a number of causes (excess fructose, linoleic acid (n-6), sedentism, inflammation, sleep disturbances…) and a shocking number of consequences. Most common are Type 2 diabetes and obesity, but linkage to hyperinsulinim includes various types of cancer, mental decline, acne and renal problems for a short list. In the hyperinsulinemic state we have several problems we have already visited (AGE’s & inflammation) but have another interesting wrinkle: elevated growth factors. During the hyperinsulinemic state liver metabolism is, well, broken. We see a decrease in the production of sex hormone binding protein (SHBP) which can be a growth promoter, but we also see an increase in various growth factors including epithelial growth factor (EGF) which can be problematic for a number of skin conditions, and vascular endothelial growth factor (VEGF), which, (you guessed it) can damage kidney function. The structures of the nephron are literally only a few cells think at best. If these structures become damaged due to inflammation, or thickened due to abnormal growth…the system will fail. This study shows how powerful the removal of excess VEGF can be in a diabetic mouse model. The long and short is that even with the other complications associated with diabetes (AGE’s and increased inflammation) the removal of VEGF dramatically improved kidney function.
Aldosterone is a critical hormone in regulating electrolyte balance, total blood volume and blood pressure. The action of aldosterone is to cause sodium retention and potassium excretion, with the net effect being an increased blood volume. Hyperinsulinism causes increased blood volume as aldosterone production is increased in lock-step with insulin production.
Cortisol has similar effects to aldosterone (sodium retention) but is much less potent in this regard.
Hormonal Effects of sleep
This could be a long post unto itself, but I’d like to look at the action of sleep deprivation on aldosterone. Interestingly, sleep deprivation blocks the nighttime pulsitile release of aldosterone with an interesting effect…of increasing nighttime urine production. Elevated cortisol & hyperinsulinism both alter normal sleep cycles, and have as clinical manifestations, increased nighttime urine production. Which further disturbs sleep, buggaring insulin sensitivity and increasing cortisol levels. You could look at it like this: Hyperinsulinism causes us to retain sodium and water, but also tends to disturb sleep. this alters normal nighttime aldosterone production…causing the frequent trips to the privy at night.
Hey Robb! What about protein and kidneys?
Hmm…how to tackle this tactfully. In healthy kidneys protein intake has NO EFFECT on kidney health. In sick kidneys, protein can cause problems. Why? Because when the kidneys are not excreting urea bad things happen. Urea itself is not particularly toxic, but other nitrogenous waste products are neurotoxic and can cause death at high enough levels. The bottom line is that in healthy individuals, increased protein intake causes an increase in the kidneys ability to deal with creatinine and BUN. In individuals with kidney disease they will likely benefit from a decrease in protein intake…but they need to address one of the aforementioned factors if they want to REGAIN kidney function, which we will talk about soon.
Putting it all together
Nothing helps cement the learning process better than a practical example. Let’s look at someone who has all the cards stacked against them, then figure out how to pull their heinie from the flames. Here folks is Pete “Proteinuria” Paducka.
Pete is a 30 YO male, 175cm tall, 110kg (I can’t tell you hw depressing and embarrassing it is that the US can’t figure out the metric system) and pretty much a mess. He is sedentary, stressed, has terrible sleep and exists on packaged pastry products and beverages with “DEW, Pepper” and similar monikers. Recently Pete had to get a physical and he had: high blood pressure, elevated: blood glucose, BUN, creatinine. Given that his condition was obviously not good it was recommended that his renal function get checked out. Tests indicated Pete was operating on approximately 10% of normal kidney function. Pete was pretty shaken up by his condition…peri-diabetic, facing dialysis ( his doctor wanted to start dialysis IMMEDIATELY) and all at the ripe old age of 30. Fortunately for Pete, his employer was a member at a wacky little gym called NorCal Strength & Conditioning and the employers offered to not only pick up his gym membership for a few months, but would pay Pete on an incentive basis: $5 for every pound lost. This is a small IT company, and I’m sure this situation violated multiple California state “fair employment” laws…but it’s what happened here. Pete went through an initial assessment at NorCal, and it was recommended that he work with Amy Kubal on his nutrition. The course of action involved a low protein (10-15% protein) low carb ( less than 10%) high fat (mainly from coconut products), ketogenic diet. Pete’s doctor was horrified, but we petitioned for one month of “tinkering” to see how things went. Three weeks later Pete’s GFR was 80% of normal instead of the previous 10% and his BUN was within normal ranges. His doctor was interested…but baffled. Pete has subsequently titrated up his protein intake with no ill effects on kidney function.
The Tea Leaves
When you look at the etiology of most kidney diseases the approach we took with Pete addressed every damn variable all at once: autoimmunity, elevated insulin and growth factors, AGE’s…did I miss anything? Interestingly, about a week after Pete got his 80% test results back this article appeared, extolling the virtues of a ketogenic diet for renal failure. As I’m writing this I actually get ANGRY when I realize how much death and suffering occurs because insulin resistant diabetes (and all of it’s complications, like renal failure) is “managed” instead of “cured.” Unfortunately most folks are too addicted to their unhealthy lifeway to change in the way that I’ve descried here…but many will change if given the option, but our government and medical community are still in a metabolic dark ages. Sigh.
I’m sure folks will have questions, please put them in the comments and I can get to these in either a follow-up post or perhaps a podcast. I’d planned on this being substantially longer but I have some events cooking that will take me 100% out of email, phone and similar coms until early July. I’m not sure when I’ll be able to share information about that event with y’all, but I will when I can. Nicki will be Ok’ing the comments while I’m gone, podcasts are in que. Thanks for the continued support and I hope folks find this piece to be helpful.