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Genetics and Chronic Kidney Disease

Chronic Kidney Disease (CKD) is a degenerative condition linked to multiple co-morbidities and an increased risk of cardiovascular disease. In addition, the CKD etiology is linked to conditions like Diabetes Mellitus and hypertension. However, the deterioration of kidney function is not only associated with metabolic disorders, as it can also be affected by autoimmune disease. In addition, genetic conditions such as Autosomal dominant polycystic kidney disease (ADPKD) can cause a detriment to the kidney’s function and structure. Multiple gene variants link the implicated pathways involved with CKD progression and kidney filtration markers. 

eGFR and Genetic Variants

UMOD is the genetic code for the protein uromodulin. Indeed, uromodulin is a protein produced by the kidneys and is the most abundant urinary protein. 

UMOD 

Furthermore, in animal models, the loss in UMOD has a close link with the dysfunction of transmembrane solute transporters in the loop of Henle. Another disease linked to mutations in the UMOD gene is the autosomal dominant tubulointerstitial kidney disease that could progress into CKD. 

In particular, the UMOD variant rs12917707 found in patients with CKD and European ancestry associates with lower eGFR. In addition, the literature reports multiple UMOD gene variants which seem to change within ethnicities. Variations like the rs11864909 and rs13329952 were found in the Icelandic population by a large study involving 15 594 participants. Finally, this report concluded that these variations were significantly associated with CKD.

The UMOD variant rs12917707 was the first to gain clinical significance for the detection of CKD. The main reason behind this is that it has a powerful effect on the measurement of serum creatinine, eGFR, and cystatin C. Furthermore, confirming a CKD diagnosis depends on the measure of SCr eGFRcrea and eGFRcys. However, certain patients are difficult to stage because their biochemical filtration markers are on the borderline of the normal ranges. 

Elderly patients with low muscle mass, protein-energy wasting, or bedridden can falsely report low creatinine levels, affecting the eGFRcrea equation. On the contrary, patients with a high muscle mass, highly active individuals with a high protein diet due to their repair requirements, can report a higher creatinine level, reflecting on a low eGFR. 

In this particular case, which is very common, the literature shows that UMOD is associated with renal function and not with creatinine metabolism or production. In addition, previous studies consider UMOD as a diagnostic biomarker of CKD.

SHROOM3

This is the encoding gene for the SHROOM3 protein, which has the function to coordinate the cytoskeleton assembly. With the potential to regulate cell shape, variants in the SHROOM3 gene are associated with allograft fibrosis in transplant patients. Following UMOD, SHROOM3 rs17319721 variant is the second genetic biomarker associated with low eGFR.

Besides this variant’s association with eGFR in CKD patients, a study of 3028 Caucasian patients with DMT2 showed a powerful impact on albuminuria. Finally, this finding may imply the functional role of the shroom3 protein in proteinuria.

Cystatin C rs13038305

The KDIGO recommends using an alternative filtration marker cystatin C to determine CKD staging when creatinine-based eGFR cannot be used as a reliable marker. In addition, cystatin C has proven to be a promising biomarker of renal function since it does not reflect factors such as race and muscle mass.

However, studies show that carriers of the T allele of the SNP rs13038305 report a higher level of cystatin C. Therefore, the reporter glomerular filtration rate in these patients seems higher, resulting in misdiagnosis. 

A study performed to observe how the rs13038305 affected glomerular filtration found the following results:

  • Those patients with the rs13038305 had 6.4% lower cystatin levels.
  • This low cystatin C level translated to 5.5-mL/min/1.73 m2 higher eGFRcys.
  • The odds of suffering from CKD lowered a 36% in the T allele carriers.

These findings raised questions about the necessity to adjust the genetic bias in the eGFRcys equation. In addition, when adjusting for genetic variant, 7.7% of the participants were reclassified to a higher staging of CKD progression. 

Chronic Kidney Disease is a complex condition that requires multiple stages of assessment. As knowledge progressed, studies showed the other shortages of creatinine and eGFR. However, the combination of these markers with cystatin C seems to be promising. In addition, genetic variants that play an essential role in the kidney’s structure and function are now considered critical biomarkers to detect CKD.- Ana Paola Rodríguez Arciniega, MS.

 

References:

Cañadas-Garre, M et al. “Genomic approaches in the search for molecular biomarkers in chronic kidney disease.” Journal of translational medicine vol. 16,1 292. 25 Oct. 2018, doi:10.1186/s12967-018-1664-7

O’Seaghdha, Conall M et al. “Association of a cystatin C gene variant with cystatin C levels, CKD, and risk of incident cardiovascular disease and mortality.” American journal of kidney diseases: the official journal of the National Kidney Foundation vol. 63,1 (2014): 16-22. doi:10.1053/j.ajkd.2013.06.015

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Disclaimer

 

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.* 

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. Read More.

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

email: coach@elpasofunctionalmedicine.com

phone: 915-850-0900

Licensed in Texas & New Mexico

 

Post Disclaimers

Professional Scope of Practice *

The information herein on "Genetics and Chronic Kidney Disease" is not intended to replace a one-on-one relationship with a qualified health care professional or licensed physician and is not medical advice. We encourage you to make healthcare decisions based on your research and partnership with a qualified healthcare professional.

Blog Information & Scope Discussions

Our information scope is limited to Chiropractic, musculoskeletal, physical medicines, wellness, contributing etiological viscerosomatic disturbances within clinical presentations, associated somatovisceral reflex clinical dynamics, subluxation complexes, sensitive health issues, and/or functional medicine articles, topics, and discussions.

We provide and present clinical collaboration with specialists from various 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 directly or indirectly support our clinical scope of practice.*

Our office has reasonably attempted 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, DC, or contact us at 915-850-0900.

We are here to help you and your family.

Blessings

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

email: coach@elpasofunctionalmedicine.com

Licensed as a Doctor of Chiropractic (DC) in Texas & New Mexico*
Texas DC License # TX5807, New Mexico DC License # NM-DC2182

Licensed as a Registered Nurse (RN*) in Florida
Florida License RN License # RN9617241 (Control No. 3558029)
Compact Status: Multi-State License: Authorized to Practice in 40 States*
Presently Matriculated: ICHS: MSN* FNP (Family Nurse Practitioner Program)

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  1. General Disclaimer *

    The information herein is not intended to replace a one-on-one relationship with a qualified health care professional, or 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 healthcare 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*

    Dr. Alex Jimenez DC, MSACP, CIFM, IFMCP, ATN, CCST
    My Digital Business Card

Post Disclaimers

Professional Scope of Practice *

The information herein on "Genetics and Chronic Kidney Disease" is not intended to replace a one-on-one relationship with a qualified health care professional or licensed physician and is not medical advice. We encourage you to make healthcare decisions based on your research and partnership with a qualified healthcare professional.

Blog Information & Scope Discussions

Our information scope is limited to Chiropractic, musculoskeletal, physical medicines, wellness, contributing etiological viscerosomatic disturbances within clinical presentations, associated somatovisceral reflex clinical dynamics, subluxation complexes, sensitive health issues, and/or functional medicine articles, topics, and discussions.

We provide and present clinical collaboration with specialists from various 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 directly or indirectly support our clinical scope of practice.*

Our office has reasonably attempted 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, DC, or contact us at 915-850-0900.

We are here to help you and your family.

Blessings

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

email: coach@elpasofunctionalmedicine.com

Licensed as a Doctor of Chiropractic (DC) in Texas & New Mexico*
Texas DC License # TX5807, New Mexico DC License # NM-DC2182

Licensed as a Registered Nurse (RN*) in Florida
Florida License RN License # RN9617241 (Control No. 3558029)
Compact Status: Multi-State License: Authorized to Practice in 40 States*
Presently Matriculated: ICHS: MSN* FNP (Family Nurse Practitioner Program)

Dr. Alex Jimenez DC, MSACP, RN* CIFM*, IFMCP*, ATN*, CCST
My Digital Business Card