Kidney Scientist Reveals What is Damaging Most People’s Kidneys

Intro (0s)

• Metabolic health is important to every single organ system, and every cell requires molecules to make energy and perform their own metabolism, with all cells talking to one another back and forth (50s).
• Metabolism is not just about creating energy, but also about the communication between different systems, with cells being analog systems that respond to a baseline level of inputs (1m41s).
• The way cells work is by detecting inputs against a baseline and then propagating a signal depending on how far away from the baseline it is, with this signal being able to be disrupted in different ways (2m55s).
• Glucose is a big lever that affects metabolic health, but it's not the only one, with fats, saturated fats, and other molecules also playing a role in regulating metabolic health (3m15s).
• The big levers of metabolic health include glucose, fats, and other energy molecules, as well as factors like not eating, which can cause a change in the homeostatic regulator (3m30s).
• All substances, including macro molecules like carbohydrates, proteins, and fats, as well as the substances they are made of, play a role in regulating metabolic health (4m7s).
• Metabolic health is about finding a balance between signals, with cells responding to changes in inputs and adjusting their baseline level accordingly (2m6s).
• Every tissue participates in metabolism in some way, and metabolic health is important to every single organ system (55s).
• The liver is often focused on in discussions of metabolic health because it regulates fats and glucose in the body, but other organs and systems also play important roles (1m2s).

How Kidneys Affect Metabolic Health (4m16s)

• The kidneys play a crucial role in overall metabolic health, not just filtering and waste removal, and are often overlooked in discussions about metabolism (4m18s).
• The kidneys consume a lot of fat and are energy-intensive organs due to their constant function of sodium and potassium pumping, requiring a lot of energy and having many mitochondria (5m20s).
• The kidneys regulate fat metabolism by soaking up fatty acids from the blood into lipid droplets and slowly releasing them back into circulation to buffer the overall fat content of the blood (5m56s).
• This regulation of fat metabolism is accelerated in someone in a fasted state, with more liberation of fat (6m11s).
• The kidneys' regulation of fat metabolism is influenced by the amount of fat in the blood, with higher serum concentrations leading to more fats accumulating in the kidney tissue (7m0s).
• The relationship between fat adaptation, fasting, or a ketogenic diet and kidney function is not well-researched, and it is unclear if the kidneys communicate with cells to regulate fat or ketone affinity (6m54s).
• Fat droplets in the kidneys are generally considered negative and a sign of pathology, indicating high fatty acid levels in the blood (7m26s).
• The kidneys use lipid droplets for energy and buffer the total fat in the blood, having a dual function under normal conditions (7m42s).
• Under pathological conditions, lipid droplets can accumulate and cause toxic byproducts, contributing to kidney disease (8m25s).
• Research from the Williams Lab at the University of California, Santa Barbara, suggests that ketones can impact the progression of chronic kidney disease, and a ketogenic diet can be beneficial (8m52s).
• Beta-hydroxybutyrate, the main ketone body, can provide the kidneys with an alternative fuel source, reducing stress and potentially slowing the progression of chronic kidney disease (9m12s).
• KetoCitra, a non-prescription formula, contains beta-hydroxybutyrate and can help manage polycystic kidney disease and other chronic kidney conditions by providing an alternative fuel source, binding to harmful dietary components, and preventing the formation of kidney stones (8m34s).
• The kidneys can regulate fat levels by releasing or storing them, depending on energy needs, and may be able to adapt to different energy sources, such as in athletes who are fat-adapted (10m32s).
• KetoCitra can also help bind to harmful dietary components, reducing potential stress on the kidneys, and prevent the formation of microcrystals that can accumulate and lead to kidney stones (9m28s).
• The process of studying kidney damage is complex and challenging, as it would require a biopsy of the kidney during specific times to observe the changes, which is difficult to do without causing harm to the individual (11m8s).
• To gain a deeper understanding of kidney damage, researchers could potentially conduct studies on animals, but this would also be a very difficult study to undertake (11m27s).
• Currently, there is limited information available on the practical effects of kidney damage due to the challenges associated with studying it (11m13s).

Healthy Kidney vs Unhealthy Kidney (11m35s)

• A healthy kidney functions by using a lot of fatty acids for energy, regulating sodium and potassium, and managing other solutes, with the mitochondria playing a significant role in this process (11m53s).
• Under normal conditions, the kidneys are able to efficiently burn through fats through fatty acid oxidation (12m10s).
• In metabolically unhealthy individuals, mitochondrial damage can occur, leading to the accumulation of fats and the need to break them down through an alternative pathway (12m17s).
• This alternative pathway results in the production of oxidized compounds that can cause inflammation and have other effects, depending on the type of fat being oxidized (12m23s).
• The type of fat being oxidized in this pathway can lead to various outcomes, with different effects on the body (12m33s).

How Does a Low-Carb Diet Affect the Kidneys? (12m40s)

• A low-carb state can lead to lower insulin levels, resulting in a higher propensity for muscle cramps due to potential fluid regulation issues, which may not be resolved by increasing salt intake (12m47s).
• Muscle cramps in a low-carb state may be related to an imbalance between sodium and potassium levels, and adding sodium can help alleviate the issue (13m42s).
• The kidneys may experience a natriuretic effect in a low-carb state, leading to excess sodium excretion, which could contribute to muscle cramps (13m50s).
• The sodium-glucose transporter (SGLT) plays a role in regulating sodium and potassium balance, and a low-carb state may affect this process, potentially leading to imbalances (14m3s).
• A low-carb diet, such as a ketogenic diet, can help regulate fluid balance and reduce water retention due to lower carbohydrate and insulin levels, but may also lead to increased urination (15m23s).
• Some individuals may experience interplay between their kidney function and a low-carb state, with potential effects on fluid regulation and electrolyte balance (15m38s).

Effect of Ketones on the Kidneys (15m40s)

• Many people believe that being in ketosis is bad for the kidneys, but research suggests this may not be the case, with ketones potentially having both positive and negative effects on the kidneys (15m58s).
• Ketoacidosis, a metabolic state where the body overproduces ketones despite high glucose and fatty acid levels in the blood, is usually when ketones are bad for the kidneys, causing acidification of the blood and other negative effects (16m23s).
• Under normal conditions, the kidney is an energy-demanding organ that predominantly uses fatty acids, and different parts of the kidney's nephron have different energy requirements (16m42s).
• The upper part of the nephron's cells produce beta-hydroxybutyrate (BHB), a type of ketone, while the lower part can use it, and there are changes in BHB concentration along the nephron (17m22s).
• The nephron controls solute concentrations to regulate water and solute removal, and ketones play a role in this function, with a mechanism to pull BHB back across the nephron to increase the flow of substances through it (18m1s).
• Ketones can increase the glomerular filtration rate (GFR), which is the rate at which substances are filtered through the kidney, and different parts of the nephron may respond differently to ketones (18m33s).
• Ketones have various functions beyond energy production, and their effects on the kidneys are complex and multifaceted (18m52s).
• The kidneys have multiple functions, but the energy part is often the main focus, whereas other functions, such as using fatty acids, are likely more relevant, especially since nephrons produce BHB even when not in a dietary ketogenic state (18m55s).
• The kidneys are an aerobic system and the second ketone-producing organ, after the liver, but the ketones produced in the kidneys are not liberated into the bloodstream and are instead localized (19m20s).
• The ketones produced in the kidneys are pulled back in through a transporter called monocarboxylate, and research has shown that the kidneys contribute a significant amount to ketone production, even in non-ketogenic states (19m40s).
• If someone is in a nutritional ketogenic state, they may potentially become more efficient at producing ketones in the kidney, similar to the liver, although there is no specific research on this topic (20m7s).
• The kidneys may adapt to become more efficient at producing ketones over time, similar to other homeostatic regulators, and this adaptation may be retained even after cycling off a ketogenic diet (20m40s).
• Retaining some of the efficiency gained from being keto-adapted may potentially increase kidney function, even in the absence of dietary ketosis, and this adaptation may be similar to those gained through exercise, such as increased bone density (21m23s).
• Mitochondrial density in the kidneys, like other adaptations, may not be lost quickly, even after stopping a ketogenic diet or exercise routine (21m56s).
• Aerobic exercise or a training block for a couple of years can establish good metabolic health and mitochondrial health, which are retained for some time and do not disappear overnight (22m3s).
• Mitochondrial adaptations in the kidneys are retained after a period of good metabolic health and mitochondrial health, and it takes time for these adaptations to be lost (22m12s).
• Research has shown that mitochondrial number in the kidneys increases with BHB (beta-hydroxybutyrate), as measured by the copy number of DNA in the kidneys (22m24s).
• There is limited research on the effect of exercise on mitochondrial density in the kidneys, but it is likely that exercise has a positive impact on mitochondrial density (22m44s).

Kidneys as a Metabolic Arm (22m50s)

• The kidneys are considered a metabolic arm, a concept that may not be widely recognized or thought about, despite making sense once explained (23m2s).
• Exercising is beneficial for various parts of the body, including muscles, the heart, and mitochondria, but its impact on independent organ systems like the kidneys is often overlooked (23m9s).
• The kidneys play a crucial role as an independent organ system that is affected by overall health and wellness, including exercise and metabolic processes (23m13s).

Exogenous Ketones (23m18s)

• Exogenous ketones, such as ketone salts or monoesters, may have a similar impact on the kidneys as a ketogenic diet, even for those who do not follow the diet (23m27s).
• Research on animals has shown that beta-hydroxybutyrate (BHB) can recapitulate some of the effects of fasting and time-restricted feeding on the kidneys (24m8s).
• A study presented at the APS conference found that administering BHB to animals resulted in similar effects as those seen with fasting and time-restricted feeding, including some benefits for polycystic kidney disease (24m11s).
• The effects of BHB on the kidneys are not fully understood, but it has been shown to recreate some of the primary outcomes of polycystic kidney disease in a disease model (24m37s).
• BHB supplements may have the potential to provide some of the same benefits as a ketogenic diet or fasting for kidney health, although more research is needed (24m44s).

Polycystic Kidney Disease (PKD) (24m50s)

• Polycystic kidney disease (PKD) is a genetic form of chronic kidney disease, characterized by the accumulation of large cysts on the kidney that replace normal healthy tissue, leading to a loss of nephrons and a decline in kidney function (25m9s).
• Chronic kidney disease is a progressive disorder that affects everyone, but the rate of progression varies from person to person, with some individuals experiencing a faster decline in kidney function due to factors such as injury or scarring (25m22s).
• PKD is an accelerated form of chronic kidney disease, with a more rapid progression due to the genetic component, and can lead to end-stage renal disease and the need for a kidney transplant (26m13s).
• Cyst formation in the kidneys is a response to injury or damage, and is a mechanism used by the kidney to wall off an area that it cannot deal with, but in the case of PKD, these cysts do not usually go away and can continue to accumulate (27m2s).
• The relationship between PKD and ketones is not fully explained in the provided text, but it is mentioned that ketones may have potential benefits for PKD, although this is not elaborated upon (24m50s).
• When a cyst forms in the kidney, it can cause a portion of kidney function to be lost, as the cyst comes from the nefron itself and the cells inside the nefron start to propagate, eventually pinching off and forming a cyst (28m3s).
• Polycystic kidney disease (PKD) is a condition where cysts form at a rapid rate, often due to a genetic mutation, but research suggests that injury is the real culprit, and a triggering event is needed to initiate the cyst formation (28m35s).
• PKD is not just a disease caused by a single mutation, but also causes mitochondrial dysfunction, leading to a change in the morphology of mitochondria, a loss of mitochondria, and a shift to glycolysis as the primary energy system (29m11s).
• This shift to glycolysis is an injury response, often caused by inflammation, and cells switch to this glucose mechanism as a normal response to injury, but in PKD, cells stay in this state and propagate inflammation (29m37s).
• Beta-hydroxybutyrate (BHB) or ketones have anti-inflammatory effects and can affect macrophages, white blood cells that surveil the kidney and play a critical role in the inflammatory response and progression of PKD (30m11s).
• BHB can affect the switching of macrophages between different modes, such as surveilling and active repair or injury modes, and can stop the progression of PKD (30m37s).
• BHB also has a mitochondrial effect, making it easier to make energy through mitochondria, and can change the cell over to fatty acid metabolism by interacting with transcription factors (31m0s).
• Fatty acid metabolism is involved in kidney disease, and BHB's interaction with transcription factors can turn on the genes involved in fatty acid metabolism, which are often downregulated in kidney disease (31m20s).
• Kidney disease, specifically Polycystic Kidney Disease (PKD), can be genetically triggered, causing the genes to be expressed more, leading to the development of the disease (31m26s).
• A common misconception is that a ketogenic diet is bad for the kidneys, but in reality, it may be beneficial for kidney health (31m43s).
• The ketogenic diet has been unfairly criticized for its potential impact on kidney health, despite being one of the better options for kidney health (31m51s).

bHB & Inflammation (31m54s)

• BHB (beta-hydroxybutyrate) has been researched for its effects, particularly in relation to the LRP3 inflammasome and its role in inflammation (31m54s).
• BHB also inhibits the NLRP3 inflammasome, which is a key initiator of pro-inflammatory responses, including the secretion of cytokines that activate the inflammatory response in nearby cells (32m5s).
• The NLRP3 inflammasome is involved in the progression of injury and is responsible for activating the inflammatory response through the secretion of cytokines, and BHB's inhibition of this process can prevent this downstream cascade (32m40s).
• In the context of the kidney, the epithelial cells are important in this process, as they are the cells that would be affected by the NLRP3 inflammasome (32m17s).
• The NLRP3 inflammasome is also involved in the activation of various pro-inflammatory pathways, including the IL-1β and TNF-α pathways (32m28s).
• BHB's inhibition of the NLRP3 inflammasome can prevent the progression of injury and reduce inflammation (32m46s).
• Macrophages have a receptor called GPR109a, which is a receptor for BHB, and this receptor is important for the type switching effect in macrophages (32m51s).
• The type switching effect in macrophages is related to the receptor GPR109a and the effect of beta-hydroxybutyrate (BHB) on this receptor (33m1s).

Can You Quickly Improve Kidney Health? (33m24s)

• The anti-inflammatory effect of a ketogenic diet is not just localized, but can also reduce systemic inflammation in the body by targeting the pathway that causes the release of cytokines, which can circulate and affect tissues throughout the body (33m54s).
• Reducing processed foods from the diet can lead to improved metabolic health and reduced chronic inflammation, which can be beneficial for people with metabolic issues (34m38s).
• The exact timeframe for seeing pathological differences in the kidneys after introducing a ketogenic diet or using ketone salts is unclear, but it is likely to be a relatively quick process, potentially happening within a few weeks (35m14s).
• Research has shown that changes in metabolic health can occur rapidly, with changes in protein production and metabolic machinery happening within a few weeks of starting an exercise regimen or making dietary changes (35m43s).
• A company called Santa Barbara Nutrients has developed a product that applies research on ketone salts in a practical way, potentially using a mineralized form that is specific for the kidneys (36m8s).
• The product from Santa Barbara Nutrients uses ketone salts, but the specific variation and how it works is not fully explained in the provided text (36m21s).
• The research behind the product from Santa Barbara Nutrients was conducted at UCSB, where the founder has been working on combining research from multiple projects (36m35s).
• Research on ketosis and Polycystic Kidney Disease (PKD) led to the development of a combination of beta-hydroxybutyrate (BHB) and citrate to prevent the progression of PKD, with a synergistic effect when used together (36m50s).
• The combination of BHB and citrate, along with other ingredients, was formulated into a product called KetoCitra, which has been on the market for a few years and is designed to support kidney health (37m46s).
• KetoCitra contains a ratio of BHB and citrate based on research, as well as calcium, magnesium, and potassium, with no sodium, as sodium can worsen PKD progression (37m56s).
• Potassium is included in KetoCitra because it is important for kidney function and often under-supplemented, with many people having low potassium levels (38m14s).
• Magnesium and calcium are included to bind to compounds in the gut that can cause kidney stones, such as oxalate and phosphate (38m32s).
• The combination of ingredients in KetoCitra provides an alkali base, increasing urine pH and preventing crystal formation, with citrate also binding to calcium in the urine to prevent crystal formation (38m54s).
• The product was originally developed for PKD but may have applications for general kidney health, with potassium and alkali already shown to be beneficial for kidneys (39m35s).
• Research has shown that supplementing with potassium chloride can be beneficial for kidneys, and adding alkali and potassium may significantly improve kidney health (39m55s).
• Increasing the amount of NADH produced in the kidneys can be achieved by changing the barrier and lowering it to make more energy by increasing the alkali in the cells, which has been shown to have beneficial effects in research studies (40m16s).
• Adding bicarbonate to cells can increase the production of NADH, and increasing the alkali in the urine is already a good thing, as it can prevent kidney injury and the formation of microcrystals (40m30s).
• Citrate can prevent the formation of microcrystals, which can cause kidney injury, and having citrate available can prevent this issue (41m1s).
• BHB (beta-hydroxybutyrate) has numerous functions, including anti-inflammatory benefits, and can have a beneficial effect on normal kidneys (41m7s).
• The crystals themselves can cause injury to the kidneys, and oxalate crystals have a receptor that causes free radical damage, activates the inflammasome, and causes kidney injury (41m28s).
• Oxalates can cause kidney injury and have a negative impact on the kidneys, and the data suggests that consuming oxalates is not good for kidney health (43m22s).
• Even raw vegetables can contain high amounts of oxalates, which can be detrimental to kidney health (43m28s).
• KetoCitra is a supplement that contains citrate and BHB, and it can be found on the website Santa Barbara Nutrients.com, which may be beneficial for kidney health (42m11s).
• Exogenous ketones, such as those found in KetoCitra, can have a beneficial effect on the body, even if kidney health is not the primary focus (42m32s).
• The kidneys have evolved to deal with oxalate, a naturally occurring compound that is produced when the body breaks down carbon to obtain energy, and is present everywhere in the environment, (43m34s).
• The body has developed mechanisms to deal with oxalate, including the production of citrate, which helps to prevent the formation of oxalate crystals, and osteopontin, which binds to these crystals and helps to remove them from the body, (44m1s).
• In the past, the body may have had help from bacteria in the microbiome that could break down oxalate, but the use of antibiotics and other factors have depleted these bacteria, leaving the body more exposed to the negative effects of oxalate, (44m26s).
• Consuming citrate, such as through eating foods high in citrate or taking citrate supplements, can help to prevent the formation of oxalate crystals, which can be beneficial even for people who consume a lot of oxalate-rich foods like spinach, (44m56s).
• Oxalate is not just a problem for the kidneys, but can also accumulate in other tissues, such as the connective tissue and the thyroid, and cause damage, (45m27s).
• Cooking vegetables does not break down oxalate, but consuming calcium with oxalate-rich foods can help to reduce the absorption of oxalate into the body, (45m51s).
• Oxalate is a highly stable compound that cannot be broken down by heat or other means, and can survive in sediment and other environments, (46m34s).
• Citrate binds to the calcium part of oxalate, preventing it from clustering into crystals, but it does not eliminate oxalate from the body (46m55s).
• Consuming calcium with a meal can help bind to free oxalate, allowing it to be excreted through feces, rather than being absorbed into the bloodstream (47m5s).
• If free oxalate is present, it will diffuse into the bloodstream, and the kidneys will have to deal with it (47m17s).
• Foods high in free oxalate, such as spinach, can increase the amount of oxalate in the body (47m25s).
• There is a difference between high oxalate content and free oxalate content in foods, with soluble and insoluble oxalate being distinct (47m37s).
• Plants use oxalate crystals for defense purposes and to store calcium, and some plants contain phytic acid, which binds to magnesium (47m47s).
• Soluble oxalates are the free versions that easily make their way into the blood, while insoluble oxalates are in crystalline form (48m9s).
• Research on oxalate content in foods is limited, and there is no comprehensive table of oxalate-containing foods (48m19s).
• Sally Norton, known as the "Oxalate Queen," has compiled resources on oxalate-containing foods, but the data is not always reliable due to variations in testing and reporting (48m31s).
• Calcium and magnesium can bind to oxalates in food and the gut, potentially reducing their absorption into the bloodstream (49m23s).