Chronic Kidney Disease and HyperHomocysteinemia

The physiopathology of Chronic Kidney Disease (CKD) includes a wide variety of signs and symptoms. Indeed, the structural dysfunction followed by a decrease of glomerular filtration rate is accompanied by microalbuminuria, anemia, inflammation, and oxidative stress. Consequently, the interaction among these physiological disturbances increases cardiovascular morbidity and mortality in this population. Undoubtedly, hyperhomocysteinemia has a central role in this cardiovascular development and DNA methyltransferases inhibition, affecting epigenetic control due to high uric acid levels. However, vitamin B supplementation has an impactful role in controlling homocysteine levels and modulating epigenetic changes through DNA methylation in patients with CKD.

CKD, atherosclerosis, and hyperhomocysteinemia:

Among the multiple CKD complications, hyperhomocysteinemia (HHcy) is present due to impaired metabolism and excretion. However, this increase in homocysteine levels strongly associates with the promotion of atherosclerosis due to elevated oxidative stress levels, thrombosis induction, and disrupted endothelial function. The following three mechanisms describe HHcy in the atherosclerotic process.

  1. HHcy causes arterial wall injury and release of oxidized LDL.
  2. Circulating monocytes migrate to the site of injury, triggering inflammation.
  3. Arterial wall cells proliferate to heal the lesion, resulting in plaque formation.

Vitamin B supplementation, HHcy, and CKD.

Vitamins like pyridoxine (B6), folic acids (B9), and cobalamin (B12) are critical modulators of homocysteine levels. In a healthy population, the nutritional supplementation of these methyl donor vitamins would control the HHcy preventing deranged epigenetic changes. However, in CKD, the renal progression is due to factors like oxidative stress, inflammation, and an increase of uremic toxins that affect epigenetic dysregulation. 

  • DNA methylation: is catalyzed by enzymes responsible for the transfer of a methyl group from S-adenosyl methionine. DNMT’s are the enzymes capable of transferring a cytosine residue, resulting in DNA hypermethylation leading to gene silencing.
  • Dioxygenases catalyze DNA demethylation: potentiated by the TET (ten-eleven translocation) protein family. This action results in DNA hypomethylation and transcriptional induction. In the CKD population, genomic hypomethylation relates to accelerated aging.

DNA coding and Methylation:

The correct function of DNA methylation relies on the availability of methyl donors, principally folic acid, methionine, choline, and betaine. Besides this mechanism, the uremic state heavily influences the methyl transference in patients with CKD.

MTHFR is one of the encoding genes affected by nutritional intake, filtration capacity, and CKD’s metabolic status. Indeed, a silenced MTHFR gene expression is highly associated with lower levels of eGFR.

In addition, Hsu et al. reported the impact of higher uremic levels and DNA methylation by DNMT in patients undergoing hemodialysis (HD). This study reported no association between DNA methylation and higher uremic and homocysteine levels for patients intervened with HD. However, another study compared DNA methylation among hemodialysis patients, high-flux hemodialysis patients, and controls. This study concluded that HD patients had significantly higher methylation when compared to high-flux hemodialysis patients.

Clinical applications:

Multiple studies have proven the effectiveness of supplemental vitamin B for CKD patients. Relevant information concludes that the potential of methyl donors to lower homocysteine levels is crucial to prevent CVD complications in patients with CKD. Nevertheless, it is essential to mention that filtration dysfunction and hyper uremic state may influence the methylation capacity.

Folic acid and 5-MTHF

In a 2008 study, Cianciolo reported a homocysteine decrease of 50% on those hemodialysis patients treated with 50mg 5-MTHF iv vs. those supplemented 5 mg of folic acid orally. Additionally, those patients who were intervened with 5-MTHF reduced inflammatory markers, such as CRP, and increased their survival rate.

Two meta-analyses performed by Qin et al. concluded that daily supplementation of 5 mg of folic acids reduced cardiovascular risk by 15% on patients with ESRD and reduced homocysteine levels.

Vitamin B12

A short pilot interventional study supplemented 1000 mcg of intramuscular vitamin B12 weekly for a month and then monthly for three consecutive months. Furthermore, this supplementation supported erythropoietin support, reflecting a stable hemoglobin level.

Nutritional supplementation of vitamin B promotes methylation by modulating homocysteine levels in patients with CKD. The balance between nutritional intake and proper filtration enables a better clinical outcome for patients undergoing CKD treatment. Methyl donors help the proper DNA methylation and transcription, resulting in lower medicine needs, reduced risk of cardiovascular disease, and prevents anemia in CKD patients.- Ana Paola Rodríguez Arciniega, MS.

References:

Cappuccilli, Maria et al. “Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.” Nutrients vol. 12,5 1234. 27 Apr. 2020, doi:10.3390/nu12051234

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The information herein is not intended to replace a one-on-one relationship with a qualified healthcare professional, licensed physician, and not medical advice. We encourage you to make your own health care decisions based on your research and partnership with a qualified health care professional. Our information scope is limited to chiropractic, musculoskeletal, physical medicines, wellness, sensitive health issues, functional medicine articles, topics, and discussions. We provide and present clinical collaboration with specialists from a wide array of disciplines. Each specialist is governed by their professional scope of practice and their jurisdiction of licensure. We use functional health & wellness protocols to treat and support care for the musculoskeletal system’s injuries or disorders. Our videos, posts, topics, subjects, and insights cover clinical matters, issues, and issues that relate to and support, directly or indirectly, our clinical scope of practice.* 

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Clinical Scope of Practice *

The information herein on " Chronic Kidney Disease and HyperHomocysteinemia " is not intended to replace a one-on-one relationship with a qualified health care professional, licensed physician, and is not medical advice. We encourage you to make your own health care decisions based on your research and partnership with a qualified health care professional. Our information scope is limited to chiropractic, musculoskeletal, physical medicines, wellness, sensitive health issues, functional medicine articles, topics, and discussions. We provide and present clinical collaboration with specialists from a wide array of disciplines. Each specialist is governed by their professional scope of practice and their jurisdiction of licensure. We use functional health & wellness protocols to treat and support care for the injuries or disorders of the musculoskeletal system. Our videos, posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate to and support, directly or indirectly, our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We provide copies of supporting research studies available to regulatory boards and the public upon request.

We understand that we cover matters that require an additional explanation of how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900.

Dr. Alex Jimenez DC, MSACP, CCST, IFMCP*, CIFM*, ATN*

email: coach@elpasofunctionalmedicine.com

phone: 915-850-0900

Licensed in: Texas & New Mexico*

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