06/10/2020
Is Klotho The New Superstar In Kidney Disease?
In its early stages, kidney disease has no symptoms and isn’t easily detected which makes it difficult to make an early and accurate diagnosis. Frequently, people aren’t aware they have kidney disease until they have already reached the later stages and a lot of kidney damage has already occurred.
Today I want to introduce you to something that has the potential to change the face of kidney disease. There’s a new protein in town (and by new I really mean twenty years old!) that researchers are hoping will provide a new (and more effective) treatment for both acute and chronic kidney disease.
Introducing……….. Klotho!
What is klotho?
Klotho is a protein found in mammals that is produced by the klotho gene. The discovery of klotho was made in 1997 and it was initially identified as an anti-ageing gene.
Like many scientific breakthroughs the discovery of the Klotho gene was a happy accident.
Klotho was originally identified as a gene in mice when a defect in klotho gene expression resulted in effects that resembled human aging, such as cognitive impairment, osteoporosis, atherosclerosis (hardening of the arteries), hearing loss and a shortened life span.
So, while a reduction of the klotho protein in mice were shown to shorten their lifespan, higher levels of klotho actually extended their lifespan. Pretty cool, huh!
Klotho takes its name from the Greek goddess of destiny. Klotho (or Clotho) is one of the Three Fates of Greek mythology who spun the thread of the lives of all mortals, deciding when they were born and when they died. Once you learn a bit more about the klotho gene you will see that this aptly named gene really is intertwined with lifespan (pun intended!).
Klotho levels are closely related to age. Its serum level is low in the first decade; it then increases and reaches its peak in the 20-40 age groups and gradually decreases thereafter.
In humans, klotho deficiency has been associated with the development of atherosclerosis, diabetes, high blood pressure, chronic kidney disease, osteoporosis, anaemia, and various cancers.
The role of Klotho in Kidney Disease
There is unequivocal evidence in experimental animals that both acute kidney injury (AKI) and CKD are states of systemic klotho deficiency.
Most of the klotho in the body is produced in the kidneys which means that the more kidney damage you have, the less klotho they can make which then results in further damage which becomes a bit of a vicious cycle.
Soluble Klotho is the main functional form in the circulation and is detected in the blood, urine and CSF (cerebrospinal fluid).
Evidence shows that klotho deficiency develops in very early stages of CKD as a response to albuminuria (albumin in urine), kidney inflammation or even inflammation elsewhere in the body.
Having a reliable method of measuring klotho levels could potentially be a game changing development that allows for earlier diagnosis of kidney disease which is desperately needed because the earlier we know about a problem, the sooner we can do something about it.
The actions of klotho in the kidneys include:
Protection of the cells in the kidney
Reduction in oxidative stress
Anti-fibrosis- renal fibrosis is like scarring in the kidneys which results in progressive loss of kidney function and can ultimately lead to end-stage renal failure
Reduces inflammation
Protection against vascular calcification and mineral bone disease (a consequence of later stages of kidney disease)
Inhibits phosphate absorption and promotes excretion of phosphate in urine
Klotho was originally identified as a gene in mice when a defect in klotho gene expression resulted in effects that resembled human aging, such as cognitive impairment, osteoporosis, atherosclerosis (hardening of the arteries), hearing loss and a shortened life span. %