Dogs have under a million nephrons in each kidney. Depending on what stage of kidney disease your dog is in, will mean your dog has less functioning nephrons.
A nephron is a functional unit made up of many different types of cells, including epithelial cells, podocytes, and endothelial cells.
Nephrons have mitochondria. And mitochondria are the powerhouse of the cell. They are the organelles that digest nutrients and create energy for the cell. This is called cellular respiration.
The kidney is one of the most energy-demanding organs and has the second highest mitochondrial content and oxygen consumption after the heart. Renal proximal tubular cells require high energy for reabsorption and secretion against chemical gradients.
The kidney requires a large number of mitochondria to remove wastes from the blood and regulate fluid and electrolyte balance.
And so we want to keep the mitochondria as healthy as possible when it comes to kidney disease.
The Warburg Effect and the Kidneys.
The Warburg effect is most commonly associated with cancer cells. While this video is for humans, it demonstrates this concept.
It is when cancer cells, somewhat counterintuitively, prefer fermentation as a source of energy rather than the more efficient mitochondrial pathway of oxidative phosphorylation (OxPhos).
The Warburg effect has also been observed in other diseases, such as kidney disease. In kidney disease, the Warburg effect can lead to the accumulation of urea in the blood.
Urea is a waste product that is produced by the liver and excreted by the kidneys. When the kidneys are not functioning properly, urea can build up in the blood. This can lead to a number of health problems, including kidney failure and heart disease.
There are a number of factors that can contribute to the Warburg effect in kidney disease. One factor is the loss of kidney function. When the kidneys are not functioning properly, they cannot remove urea from the blood as effectively. This can lead to a buildup of urea in the blood, which can damage the kidneys and other organs.
Another factor that can contribute to the Warburg effect in kidney disease is inflammation. Inflammation is a natural response of the body to injury or infection. However, chronic inflammation can damage cells and tissues. In kidney disease, inflammation can damage the kidneys and lead to the Warburg effect.
The Warburg effect can also be caused by changes in the metabolism of kidney cells. Kidney cells have a high number of glucose transporters, which allows them to take up glucose from the bloodstream quickly. This glucose is then used to produce energy through glycolysis.
In kidney disease, the metabolism of kidney cells can change. This can lead to an increase in the production of lactate and a decrease in the production of pyruvate. Pyruvate is a molecule that can be used to produce energy through oxidative phosphorylation. However, lactate is a waste product that must be excreted by the kidneys. When the kidneys are not functioning properly, lactate can build up in the blood and contribute to the Warburg effect.
The Warburg effect is a complex phenomenon that is not fully understood.
But we do know that reducing carbohydrates slows down the Warburg effect.
Excessive amount of dietary fructose is deleterious in the kidney. In fact, normal rats develop mild tubulointerstitial inflammation and fibrosis on high fructose diet. (Nakagawa 2021).
In mouse models, we know that improving mitochondrial homeostasis and function has the potential to restore renal function (Bhargava 2017).
In an 8-week mouse study, albumin/creatine ratios were reversed on a ketogenic diet. (Poplawski 2011).
One of the biggest problems I see with dogs diagnosed with kidney disease is well-meaning pet parents move their dogs to a low-protein diet and… feed less than the dog needs to live. In these cases we see the kidney condition get worse. The dogs lose weight, they have low energy and this malnutrition moves the kidney disease along.
They also feed a prescription diet that has refined carbs, and easy glucose which destroys kidney function and is compounded by the very simple fact that these dogs are not fed enough of the right nutrients resulting in a greater oxidative damage to the kidneys.
The Mitochondrial Diet
This approach to feeding your dog intends to improve mitochondrial health. Ideally, this diet is composed of:
- Animal protein
- Healthy fats (fish, coconut oil, avocado)
- Leafy greens
- Antioxidant-rich foods
- No starches
- No grains
- No processed foods
- No sugars (that includes fruit and honey)
- Light activity (daily walks)
- Fasting one meal a week (keep your dog hydrated with water)
Essentially This is a Species Appropriate Diet
I’ve written many articles about your dog’s kidneys.
Oftentimes your vet will instruct you to feed less protein and while I can formulate a diet many different ways, if it were my own dog that had kidney disease, I would feed them a diet structured in the way I’ve described above.
One of the most enlighting points I learned about the very first kidney studies was
- They removed 75% of the rat’s kidneys and fed a low protein diet
- They compared the lab results and while the low protein diet produced better lab results, the rats were so weak they could not even feed themselves and had to be fed dextrose to keep them alive.
This small (but important) detail is left out in the abstracts about this study. But referenced in the book by Addis.
You can read about those studies in the first article below and then peruse the rest of the CKD articles here:
Dogs need protein in their diet from animals. And the focus in deciding what to feed them should be focused on what keeps the mitochondria healthy. Kibble gives easy glucose which leads to the Warburg effect which can then increase lactase and urea in your dog’s body which is the very thing we want to avoid.
As dog parents, we are always trying to add years to our dog’s life but perhaps the better question is how can we add a better quality of life to those years?
A fresh food diet will lead to better mitochondrial health and as such may add more life, to the remaining years your dog has with you.
Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol. 2017 Oct;13(10):629-646. doi: 10.1038/nrneph.2017.107. Epub 2017 Aug 14. PMID: 28804120; PMCID: PMC5965678.
Thome T, Kumar RA, Burke SK, Khattri RB, Salyers ZR, Kelley RC, Coleman MD, Christou DD, Hepple RT, Scali ST, Ferreira LF, Ryan TE. Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease. JCI Insight. 2020 Dec 8;6(1):e139826. doi: 10.1172/jci.insight.139826. PMID: 33290279; PMCID: PMC7821598.
Nakagawa T, Sanchez-Lozada LG, Andres-Hernando A, Kojima H, Kasahara M, Rodriguez-Iturbe B, Bjornstad P, Lanaspa MA, Johnson RJ. Endogenous Fructose Metabolism Could Explain the Warburg Effect and the Protection of SGLT2 Inhibitors in Chronic Kidney Disease. Front Immunol. 2021 Jun 16;12:694457. doi: 10.3389/fimmu.2021.694457. PMID: 34220855; PMCID: PMC8243983.
Zhang G, Darshi M, Sharma K. The Warburg Effect in Diabetic Kidney Disease. Semin Nephrol. 2018 Mar;38(2):111-120. doi: 10.1016/j.semnephrol.2018.01.002. PMID: 29602394; PMCID: PMC5973839.
Podrini C, Cassina L, Boletta A. Metabolic reprogramming and the role of mitochondria in polycystic kidney disease. Cell Signal. 2020 Mar;67:109495. doi: 10.1016/j.cellsig.2019.109495. Epub 2019 Dec 6. PMID: 31816397.
Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, Mobbs CV (2011) Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 6(4): e18604. https://doi.org/10.1371/journal.pone.0018604
Mafra D, Gidlund EK, Borges NA, Magliano DC, Lindholm B, Stenvinkel P, von Walden F. Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria. Eur J Clin Invest. 2018 Nov;48(11):e13020. doi: 10.1111/eci.13020. Epub 2018 Sep 16. PMID: 30144313.
Wong KKL, Verheyen EM. Metabolic reprogramming in cancer: mechanistic insights from Drosophila. Dis Model Mech. 2021 Jul 1;14(7):1-17. doi: 10.1242/dmm.048934. Epub 2021 Jul 9. PMID: 34240146; PMCID: PMC8277969.
Charlot A, Conrad O, Zoll J. Le régime cétogène : une stratégie alimentaire efficace en complément des traitements contre le cancer ? [Ketogenic diet: a new nutritional strategy for cancer therapy?]. Biol Aujourdhui. 2020;214(3-4):115-123. French. doi: 10.1051/jbio/2020014. Epub 2020 Dec 24. PMID: 33357370.
Hannah Zulueta obtained her Certificate in Canine Nutrition from CASI Institute. She is also studying for her Doctorate in Acupuncture, Traditional Chinese Medicine, and Herbalism from the esteemed Pacific College of Health and Medicine.
She resides in San Diego with her three dogs, Maggie, Orbit, and Mr. Higgins.