Muscle Pain 

Muscle Pain & wasting (shrivelling) is a constant, debilitating & rather frustrating accompaniment during your CKD journey, in the advanced stages. It is only but one of the many myriad “complaints” arising from across multiple organs — something that’s a part & parcel of Chronic Kidney Disease (CKD).

Previously, Team ATK has simplified the concepts of “Protein in Urine“, “Blood in Urine“, “Anemia” & “Bone Pain“, in the context of CKD.

Adding to this list, today we seek to cover the significance of skeletal muscles in kidney disease and explain why muscles begin to “lose themselves” when we enter the great abyss of Chronic Kidney Disease!

But first things first.

WHY ARE SKELETAL MUSCLES SIGNIFICANT IN KIDNEY DISEASE

Among its exhaustive list of functions that our Kidneys perform, eliminating toxic cellular wastes to cleanse our blood probably takes top priority. All tissues in the body, including Muscles, rely heavily on Kidneys for “clearing-out” their metabolic wastes (or quite literally their poo!!) to get a sparkling clean ambience for survival. Speaking of muscles, upon processing nutrients from the blood (metabolism), they produce something called Creatinine. Sounds familiar? Yes, this is the very Creatinine that is regularly monitored in your blood work if you are a “CKD Sojourner”.

Creatinine is almost exclusively removed from the body through Urine via Kidneys. So when your bloodwork shows high Creatinine levels, it could be because:

• Over-production (high muscle metabolism or muscle breakdown)
• Poor clearance (Kidney malfunction)

In CKD, initially, Serum Creatinine levels rise because of its poor clearance by unwell kidneys. Later on, as the disease progresses to advanced stages, muscle wasting (breakdown) & pain become a frequent complication. This is especially so if you are on Dialysis. This muscle breakdown causes an over-production of Creatinine with an already faulty kidney “drainage” system. As a result, in the Late stages of CKD, Serum Creatinine levels rise in leaps & bounds.

SO WHY DO YOU GET MUSCLE WASTING & PAIN IN ADVANCED CKD?

Muscle wasting & a crampy, “chewing” muscle pain become a “loyal” accompaniment as Chronic Kidney Disease progresses. With this, Serum Creatinine continues to rise exponentially as well. Now, true to the complex nature of CKD, muscle wasting here has multiple reasons & mechanisms that work in tandem to “compromise muscle-fibre strength & integrity”. This weakens muscles, makes them incapable of “supporting our body weight” & tire them out easily. Generally speaking, that is what contributes to the chewing muscle pain that most of us have encountered during our CKD journeys and many of us are currently going through. Cramps during or after a dialysis session have a whole different explanation though.

But understanding why there is muscle breakdown in CKD will allow you to truly make sense of that extensive & sometimes overwhelming pill-cocktail that becomes a companion during your CKD Journey.

Team ATK aims to reach out to all you valuable Kidney Warriors out there and help you face the challenges / difficult health outcomes that CKD sends your way, with confidence. And what better than arming yourself with the understanding of why your body reacts in a certain way to CKD?!

 

Hence, we seek to walk you through:

• The effect of the CKD disease process on muscles
• How dialysis (especially Hemodialysis) may propel muscle loss (which is actually preventable!)
• The manner in which some of your blood pressure meds in CKD may be “complicit” in thinning your muscles
• If the root disease that caused your kidneys to start losing function (such as Diabetes) has a role in muscle wasting

Let’s start learning then, shall we? So here goes:

MUSCLE LOSS DUE TO THE KIDNEY DISEASE PROCESS

Chronic Kidney Disease is complicated. There is no one reason why it affects muscle bulk negatively in advanced stages, but a whole cascade of mechanisms that act simultaneously to bring about muscle loss. Let us explain.

OVERTLY ACIDIC BLOOD

One of the important functions of our kidneys is to precisely regulate the pH of our blood between a specific range such that it is neither too acidic nor too alkaline. The onset of Chronic Kidney Disease disrupts this delicate balance that ultimately renders our blood overtly acidic. This is a frequent complication in CKD and is technically termed “Metabolic Acidosis”.

When our muscles receive acidic blood over a prolonged period of time, they are not able to produce enough new stock of the special proteins necessary to retain the strength & bulk of muscle fibers anymore. Moreover, acidosis also compromises the integrity of the existing muscle proteins by triggering something called the “Ubiquitin-Proteasome System” or UPS within individual muscle cells. This further weakens the muscle fibers and starts the process of Muscle Loss in advanced CKD. (1);

“INSULIN RESISTANCE”

Insulin is a hormone produced within our body that primarily keeps our blood glucose levels in check, thereby preventing Diabetes. What has “Insulin” got to do with Muscle loss, you may ask.  Well, for the blood glucose-lowering action to commence, Insulin Molecules are required to go “bind” to other organs like our Skeletal Muscles, Liver, Intestines & Brain. This initiates a cascade of chemical reactions to take-up excess blood glucose for storage within these organs. Figuratively speaking, this process allows muscles to “feed on” this excess glucose. This triggers the production of “muscle-building” protein that contributes to muscle bulk.

When “metabolic acidosis” sets in during your CKD journey, it unleashes mayhem within the muscle. This literally changes the structure of the muscle fiber to the extent, that there is no scope for them to bind Insulin or any of its “lookalike” molecules on it. (2).”Insulin lookalike” refers to substances in our body called “Insulin-like ‘growth’ factors (IGF)” which resemble Insulin at the part where it “binds” to the Muscles. In other words, metabolic acidosis in CKD causes muscles to “resist” any attachment of Insulin / IGF in it. The fancy medical term for this situation is “Insulin Resistance“. This state is further aggravated if you additionally have any form of inflammation i.e. conditions whose name ends with “-itis”, such as  Nephritis (kidney), Arthritis (joints), etc.

Since Insulin Resistance effectively bars Insulin & Insulin-like “Growth” Factors (IGF1) from latching onto Muscles, it basically blocks muscles from retaining their natural bulk otherwise facilitated in part, by Insulin and IGF. Ultimately muscles end up being malnourished & thin-out. (3);

POOR NUTRITIONAL STATUS

CKD can cause loss of muscle and adipose tissue, something technically called Catabolic Disease. Patients with generalized tissue breakdown irrespective of the root condition tend to have poor appetites, leading to true malnutrition. This can be attributed to defective signaling from the part in the Brain that controls appetite/hunger. High levels of blood wastes such as Urea & Creatinine in CKD primarily engineer this outcome.

The role of defective brain signals causing a poor appetite in CKD is further corroborated by interesting research where mice with kidney disease showed improved muscle growth after Appetite-boosting mediators were injected directly into their brain. (4);

MUSCLE WASTING IN DIALYSIS

All dialysis patients, be it Hemodialysis or Peritoneal Dialysis suffer from visible changes in muscle structure and strength as kidney failure sets in. As explained in the above section, acidic blood following “metabolic acidosis”, the inability of insulin hormone to attach to muscles due to “insulin resistance” and a generalized poor nutritional state in CKD adversely affect muscle protein generation. This leads to muscle loss and is a frequent complication for most CKD patients worldwide. Starting dialysis helps to bring many of these parameters in your bloodwork to near-normal levels which allow for toning-down the intensity of these muscle-weakening factors. However, some residual, baseline muscle damage from these factors goes on.

Now, dialysis only serves to “cleanse the blood”. It has no role whatsoever in helping with any of the other Kidney Functions. And it often does so, aggressively. In CKD patients, the levels of sex hormones namely Testosterone and Estrogen are already low thanks to their excessive loss in the urine of patients who still pass it. These hormones are further lost during the process of Dialysis. Ultimately, kidney patients on dialysis end-up with a deficiency of Testosterone hormone which, in normal health has a Muscle Bulking function. As a result, muscle fibers thin-out significantly & become incapable of bearing body weight or any form of exercise without first “hurting” you.  (5)

CRAMPED MUSCLES IN HEMODIALYSIS

If you are on Hemodialysis, you must have experienced those debilitating Muscle Cramps during or right after a dialysis session? Well, this complication has a completely different story. And guess what, it is actually preventable!!

It is a common practice to adjust the fluid in the dialysis machine against which “blood-cleansing” takes place, to contain low Sodium levels. Sodium is a mineral in your blood that helps to maintain your blood pressure in normal health. However, its blood levels spike in the event of kidney disease which causes high BP. Using low sodium in the dialysis fluid facilitates the moving-out of all excess Sodium from your blood thereby helping with your BP control. Point is, sometimes this technique in Hemodialysis can cause sodium to move-out from the body too fast and too large in quantity altogether. This can reduce blood flow to your nerves & muscles. They just don’t like the “sudden break in their work-flow” and register their disdain in the form of Cramps!! (6)

MUSCLE BREAKDOWN DUE TO BLOOD PRESSURE MEDICATION

High blood pressure is a cardinal feature of chronic kidney disease. This is due to the retention of excess Sodium in your blood because unwell kidneys cannot sufficiently flush it off. Since high blood pressure is both a cause and a worsening factor for kidney disease, your medical team will put you on BP controlling meds. Most of the time these medicines either belong to the “ACE Inhibitor” class or “Angiotensin-II Receptor Blocker” (ARB) class.

• • ACE Inhibitors — Medicines whose generic chemical name ends with “-pril”. Eg: Ramipril (brand name: Cardace)
  • ARB — Medicines whose generic chemical name ends with “-sartan”. Eg: Telmisartan (brand name: Micardis)

Normally, these medicines work at a molecular level with fantastic efficiency to relax your blood vessels and reduce your BP. Simultaneously though, as a side effect of taking these meds in the long term over a few years, these medicines begin to interfere with the in-growth of new blood vessels specifically into newly forming fibers of your skeletal muscles. (7)

This effect is pronounced when you take these medicines for a prolonged period of time, as is the case with CKD patients. Now, blood vessels carry life-sustaining oxygen and nutrients to various parts of the body, including muscles.

With blockage of new blood vessel formation, new muscle fibers will be devoid of these nutrients. Such muscle fibers will suffer from malnourishment and turn “sickly”.

This is particularly interesting because the ARB group of meds (those ending with “-sartan” suffix) have actually been found to improve muscle mass when used as a short course therapy on mice with muscle loss in the lab. These positive effects are likely seen in humans as well.

So in the context of Chronic Kidney Disease

The ARB group of BP-lowering meds like Micardis (Telmisartan) initially keep muscles from losing their bulk, up until the long term side-effects of blockage of new blood vessel growth begins. It is only after this, that these medicines propel muscle weakening & pain in a CKD patient.

NOTE: These changes are completely reversible when these BP medicines stop after a kidney transplant.

ROOT DISEASE THAT LED TO CKD

Chronic Kidney Disease causes muscle wasting & pain, sure. But the root condition that led to CKD must be considered when attempting to understand the reasons for Muscle Breakdown. The most important example here would be that of Diabetes mellitus (DM), both Types 1 & 2. Both types of Diabetes can lead to CKD although it is a lot more common in Type2 DM than in Type 1.

We have explained in a previous section under “Insulin Resistance” as to how Insulin Hormone has a role in adding to the muscle bulk.

Muscle Wasting in Diabetics with CKD is directly related to Insulin hormone levels & its ability to act. Type1 Diabetics produce low Insulin levels.  For type 2 diabetics, normal insulin production in the initial stages is offset by its inability to act because of Insulin Resistance.

As a result, Muscles are not able to receive the necessary signals to produce adequate Muscle-building proteins. Hence, Diabetics experience muscle wasting.

MUSCLE DISEASE RUNNING IN THE FAMILY

Another important factor is if the CKD patient has any muscle degenerative disease that runs in their family. That would most certainly have a bearing on how well their muscle fibers maintain themselves.

OTHER LIFESTYLE FACTORS

Your general nutrition levels & your exercise regime (if any) will also influence how your muscles fare out.

The difficulty with chronic kidney disease is, it is literally a “Disease of Paradoxes”. You can try out one hack to get out of a complication but in all likelihood, it will end up worsening another complication.

Say for instance, if you want to take a protein-rich diet to gain energy and muscle-building while on your CKD journey, you will only burden your already unwell kidneys with more Urea (waste from protein digestion) to clear out.

Similarly, exercising is great! It improves blood circulation throughout your body. Muscles benefit from this by receiving a fresh stock of nutrients for sustenance. However, the more our muscles exercise, the more they will metabolize & the more Creatinine (another waste product) they end up producing. Result? Kidneys will “react” with a high Creatinine level in your blood work…..which is what makes CKD frustrating both for the patients and the treating medical team!

It’s NOT ALL BAD NEWS though!!

Firstly, all muscle changes are completely reversible once you get your Kidney Transplant!!

Besides, while muscle loss in CKD cannot be prevented, some of the meds that all members of Club CKD are put on, efficiently delay & slow down this process.

And now that after going through this article, you understand the why & how of Muscle Wasting & Pain in CKD, you are fully prepared to grasp how the treatments for this condition work. That’s the next article in the pipeline!

Okay, so that was a comprehensive write-up on the possible reasons why a CKD patient may suffer from Muscle Wasting & Pain.

Keep a tab of this space for the next article on the various medicines that help you delay & slow down muscle loss in Chronic Kidney Disease.

Till then, don’t stop asking questions about your health. The more clarity you gain about it, greater will be the relative peace of mind during your CKD journey.

Feel free to contact Team ATK with your queries on kidney disease via our Contact Form here.

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REFERENCES:

1. Muscle breakdown due to Metabolic Acidosis in CKD

2. Insulin Resistance causes Muscle Wasting in CKD 

3. Poor IGF-1 signaling due to Insulin Resistance in CKD responsible for Muscle Wasting

4. Poor appetite due to impaired hypothalamic control contributes towards Muscle Loss in CKD

5. Muscle Wasting and pain in CKD patients on Dialysis

6. Hemodialysis-induced Muscle Cramps, Nephrology section, Harrison Principles of Internal Medicine Volume II 

7. Angiotensin-II spurts new blood vessel growth in skeletal muscles