Type-2 Diabetes and Chronic Kidney Disease

advanced glycation end products blood vessels calcium chronic inflammation cytokines diabetes dialysis glucose high blood pressure hormones hyperglycemia inflammation kidney disease kidneys nf-κb obesity organ transplant ph balance polyol pathway potassium reactive oxygen species smoking sodium type-2 diabetes vitamin d Aug 17, 2024

The kidney is the most in-demand organ in the U.S — almost 90 percent of Americans on the national transplant waiting list are waiting for one. These people have end-stage chronic kidney disease (CKD).^1,2

CKD affects 37 million individuals in the country. It’s especially common among people with diabetes, as one-third of diabetic adults also have CKD.^2,3

In this article, we’ll tackle the basics of CKD, then unravel its connection with type-2 diabetes (T2D):

The kidneys and fluid balance
Other important kidney functions
What is Chronic Kidney Disease (CKD)?
How does T2D lead to CKD?
Inflammation and CKD

Keep reading to learn why your kidneys are so important in the first place.

The kidneys and fluid balance

Mainly, your kidneys remove wastes and excess fluid from your body. These bean-shaped organs help maintain a healthy balance of water, salts, and minerals — for instance, sodium and potassium — in your blood.⁴

Each of your kidneys contains over a million filtering units called nephrons. A nephron, in turn, consists of glomeruli — a network of tiny blood vessels — and small tubes called renal tubules.^4,5

A large blood vessel known as the renal artery transports blood into your kidneys. Your renal artery branches into smaller and smaller vessels until the blood reaches your nephrons. There, your glomeruli filter your blood. The filtered blood then flows back to your bloodstream through another blood vessel called the renal vein.^4,5

Meanwhile, your renal tubules reabsorb water, nutrients, and minerals that have been filtered from your blood — but that your body needs — back to your blood. The remaining fluids and wastes — now collectively known as urine — travel to your bladder via muscle tubes called ureters. Your bladder collects and stores urine until you release it by peeing.^4,5

Other important kidney functions

Your kidneys are responsible for controlling the balance between acids and bases (pH balance) in your blood. They do this by clearing your blood of excess acids.^4,5

Your kidneys also make various substances.⁵

In particular, your kidneys can make sugar (glucose) if there isn’t enough of it in your blood. They also make renin, a protein that raises your blood pressure.⁵

Plus, your kidneys produce hormones called erythropoietin and calcitriol. Erythropoietin aids your body in making red blood cells. On the other hand, calcitriol is a form of vitamin D that helps your body take up calcium. This means your kidneys contribute to keeping your bones strong.^4,5

Clearly, your kidneys perform numerous vital functions. If they get damaged and malfunction, you can get sick from waste buildup in your blood. You may also have an imbalance of salts, minerals, and acids in your body, preventing your nerves, muscles, and other tissues from working normally.^2,4

What is Chronic Kidney Disease (CKD)?

CKD is diagnosed when your kidneys have been damaged for at least three months.⁶

The disease comes in five stages. At Stage 1, your kidneys are very mildly damaged, yet still work well. At the other end of the spectrum is Stage 5, also known as kidney failure. At this stage, your kidneys have stopped working, requiring you to undergo dialysis or a kidney transplant.²

You may have CKD but not know it. In fact, nine out of 10 people with CKD are unaware of their condition. That’s because CKD usually develops slowly, and it has no obvious symptoms at first.^6,7

As CKD progresses, you may pee more often or less often than before, and your urine may become foamy. You may also get itchy or dry skin, and feel tired or nauseous. Plus, you may lose your appetite and perhaps even lose weight without trying.⁶

If you’re at a more advanced stage, your arms, legs, ankles, or feet may feel numb or swell. You may get muscle aches or cramps. You may find it hard to focus, sleep, or breathe. And speaking of breath, yours might smell like ammonia — that is, “fishy” or like urine.⁶

Certain physical and environmental factors increase your risk of CKD. They include being 60 or above and having a family history of the disease. Smoking and obesity are risk factors too.⁶

One of the most common causes of CKD is high blood pressure — it’s the second leading cause, to be exact. And the top cause of CKD? Diabetes.⁸

How does T2D lead to CKD?

Having T2D means your blood sugar (glucose) levels are consistently high. This condition is called hyperglycemia.⁹

Hyperglycemia drives CKD through multiple mechanisms. First, too much glucose stimulates the production of reactive oxygen species (ROS). These unstable molecules damage the DNA and other components of your cells, including those in your kidneys.¹⁰

Another mechanism is the polyol pathway. In this pathway, excess glucose gets converted to sorbitol. Sorbitol is a water-loving substance that cannot pass through your cell membranes. This means that sorbitol buildup can draw fluid into your kidney cells, leading to cellular stress and injury. Also, the polyol pathway reduces antioxidant activity in your kidneys, further damaging them over time.^10,11,12

Plus, hyperglycemia helps activate a group of enzymes called protein kinase C (PKC). PKC narrows the blood vessels in your glomeruli, impairing your kidneys’ ability to filter blood.^10,13

What’s more, hyperglycemia promotes the formation of advanced glycation end products (AGEs). These harmful compounds form when protein or fat combines with glucose in your blood. AGEs can bind to receptors on your kidney cells. Thus, they can trigger fibrosis (thickening or scarring of your kidney tissues), as well as inflammation.^10,14

Inflammation and CKD

Inflammation naturally occurs in response to injury sustained by your kidneys through the mechanisms described above. Inflammation involves the production of chemokines and cytokines. Such pro-inflammatory molecules, in turn, recruit immune cells like monocytes, neutrophils, and macrophages to the sites of damage. These immune cells then stimulate further production of chemokines and cytokines, further aggravating the inflammation.¹⁵

Exposure to environmental triggers also causes chronic inflammation, which eventually harms your healthy kidney cells and tissues. For instance, inflammation impairs the inner lining of your blood vessels, decreasing the flow of blood through your kidneys. This reduced blood flow means that your kidneys suffer from inadequate oxygen supply. Together, these events contribute to the progression of CKD.¹⁰

A group of proteins called nuclear factor-kappa B (NF-κB) acts as a key regulator of your body’s inflammatory response. Heightened NF-κB activity is observed in CKD (and many other diseases). Hyperglycemia is known to activate NF-κB, which partly explains the connection between T2D and CKD.^15,16

Conclusion

Your kidneys’ main job is to clean toxins and waste out of your blood. In doing so, they help maintain the balance of minerals and acids in your body. Your kidneys also produce substances like glucose, as well as proteins for regulating blood pressure, making red blood cells, and absorbing calcium.

CKD is a condition in which your kidneys sustain damage and lose function over time. It’s divided into five stages, ranging from Stage 1 (very mild) to Stage 5 (kidney failure).

CKD develops gradually and has no symptoms early on. So, you may not know you have CKD until you’re at a more advanced stage of the disease.

Diabetes is the number 1 cause of CKD. Hyperglycemia — the hallmark of T2D — drives CKD in various ways. These mechanisms include ROS synthesis, the polyol pathway, PKC activation, AGEs production, and inflammation. Hyperglycemia is also known to activate NF-κB, which induces and advances inflammation in your kidneys (and other organs, for that matter).

Because of the direct link between T2D and CKD, you can lower your risk of CKD by preventing or reversing T2D. And when it comes to fighting T2D, natural is the way to go, and food is your most effective weapon. Discover the most effective change you can make to your diet to reverse T2D — sign up for the Diabetes Diet Solution now.

References

Type-2 Diabetes and Chronic Kidney Disease

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