Sclerostin linked to elevated PH risk in patients with kidney failure

The protein, attached to blood vessel walls, can predict cardiovascular disease

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Enlarged images of the kidneys are seen on either side of a person pictured from behind while drinking from a glass.

Higher blood levels of the sclerostin protein were linked to cardiac abnormalities and an elevated risk of pulmonary hypertension (PH) in patients with kidney failure, according to a recent study.

While sclerostin itself did not increase mortality risk, the presence of PH was a significant predictor of mortality over about 4.5 years of follow-up.

“This is the first study to suggest that sclerostin is an important link to pulmonary hypertension,” the study’s researchers wrote, noting that more research will be needed to further establish the observed relationships.

The study, ”Higher sclerostin is associated with pulmonary hypertension in pre-dialysis end-stage kidney disease patients: a cross-sectional prospective observational cohort study,” was published in BMC Pulmonary Medicine.

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In people with chronic kidney disease, mineral imbalances in the blood — a feature of mineral and bone disorders (MBD) — as well as inflammation and cellular dysfunction contribute to the formation of hard calcium crystals that attach to blood vessel walls, called vascular calcification and blood vessel stiffening.

That can disrupt blood flow, thereby increasing the risk of cardiovascular diseases like PH among kidney disease patients. Characterized by an elevated pressure in the vessels supplying blood from the heart to the lungs, PH is now recognized as a major complication in kidney disease patients, where it is associated with a worse prognosis.

Sclerostin is a protein that regulates bone formation in the body. It has been implicated in the formation of MBD and vascular calcification among kidney disease patients. Moreover, the gene encoding sclerostin production was found in a study to have elevated activity in blood vessel tissue from PH patients.

Still, the role of sclerostin in kidney disease and whether it is linked to the development of PH is not fully established.

The study’s findings

In the study, the scientists measured circulating sclerostin levels among 44 kidney disease patients seen at a hospital in South Korea. They all had end-stage kidney disease, where the kidneys have failed and can no longer perform their waste-filtering functions.

All were candidates for dialysis, a treatment for kidney failure that removes waste from the blood when the kidneys cannot do it on their own, but none had not started it yet.

Patients, with a median age of 54, had an average sclerostin blood level of 184.5 picomoles per liter (pmol/L), which the researchers noted was substantially higher than levels observed in the general population.

The participants were then divided into two groups based on their sclerostin levels. Thirty-one people were in the low sclerostin group, with levels below 218.18 pmol/L, while 13 were in the high group, with values at or above that cut-off.

Echocardiography, a test that uses sound waves to take images of blood flow through the heart, indicated that patients in the high sclerostin group had significant cardiac abnormalities relative to the low sclerostin group, and higher levels of the protein were also significantly associated with the presence of PH.

Final statistical analyses indicated that high sclerostin was a significant predictor of PH, raising the risk of the cardiovascular disease by more than 40 times.

Over a median follow-up of about 4.5 years, 10 kidney disease patients developed new-onset cardiovascular events and 11 people died. New-onset cardiovascular events were not predicted by sclerostin levels.

On the other hand, the presence of PH was found to be a significant predictor of mortality, as was a measure of vascular calcification.

Altogether, “sclerostin might have a role as a molecular signal for PH,” the researchers wrote, noting that this signal could help to better identify and treat cardiovascular disease in patients with kidney failure, improving their prognosis.

“A large multicenter long-term follow-up clinical study and basic study are necessary to confirm our findings,” the team concluded.

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