Blood periostin may be key marker for kidney damage in Fabry: Study

Lowering levels of protein in patients may help kidney survival

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A squirting dropper is shown alongside four vials half-filled with blood.

Periostin, a protein associated with kidney injury, may be a valuable biomarker of Fabry disease’s related kidney damage, according to new a study in Turkey.

Researchers found that blood levels of periostin were correlated to proteinuria — the presence of proteins in the urine — which is one of the most critical indicators of kidney failure progression.

“In addition to standard ERTs [enzyme replacement therapies], periostin-reducing therapies may contribute to better kidney survival in Fabry disease,” the researchers wrote.

The study, “Is just enzyme replacement therapy enough for Fabry disease treatment? Have we missed a trick?,” was published in the journal Nefrología (English Edition).

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Periostin levels linked to poorer kidney function in patients

Fabry disease is caused by mutations in the GLA gene, which provides instructions to produce the alpha-galactosidase A (Gal A) enzyme. This enzyme breaks down fatty molecules into building blocks that cells can use.

The mutations result in an absent or dysfunctional Gal A enzyme, leading to the toxic accumulation of certain fatty molecules — particularly Gb3 and lyso-Gb3 — in small blood vessels and body tissues. The toxic buildup of these molecules leads to organ damage, particularly in the kidneys and heart.

Early treatment with enzyme replacement therapy (ERT), which delivers a functional lab-made Gal A enzyme, has been shown to slow the deterioration of kidney function in Fabry patients. However, it often does not prevent progressive kidney injury.

Inflammation and consequent fibrosis, or scarring, can start before kidney damage is clinically visible and may progress despite ERT treatment.

Secondary mechanisms in the body that contribute to kidney damage still are not fully understood. Thus, unraveling these mechanisms might be a determinant to develop new and more successful treatments for Fabry disease.

Now, researchers at the Necmettin Erbakan University, in Turkey, sought to analyze the relationship between periostin and kidney damage in Fabry disease. Periostin levels previously were found to be elevated in people with other kidney disorders, and the protein is thought to mediate kidney inflammation and scarring, therefore contributing to kidney damage.

The study included 18 Fabry patients —10 men and eight women, with a mean age of 33.3 years — with indications for ERT, as well as 22 healthy people, who served as controls. The patients were diagnosed between 2014 and 2020, and at that point had a mean age of 30. Their first symptoms had appeared at an average age of 27.1 years.

The researchers examined patients’ levels of urea, creatinine, and proteinuria collected at the time of diagnosis, before ERT. Those levels were found to be significantly elevated in those with Fabry disease compared with healthy controls. Meanwhile, the glomerular filtration rate (GFR), a measure of how well the kidneys are working, was significantly lower among patients, indicating poor function.

These results are indicative of changes in kidney function, although only proteinuria was above the normal range in patients. Importantly, proteinuria is one of the earliest and most essential indicators of kidney failure in Fabry patients.

[The] correlation between [blood] periostin levels and proteinuria in Fabry patients is important both for the indicator of renal survival and a possible future treatment target.

Periostin levels in the blood were significantly higher in patients than in healthy controls and were positively correlated with proteinuria and lyso-Gb3 levels. Higher periostin levels also were associated with a lower age at the disease symptom onset and a lower GFR.

According to the researchers, “progressive fibrosis [formation of scar tissue due to inflammation] processes caused by periostin in patients with Fabry disease are still a hidden issue waiting to be clarified.”

Considering that those patients with high proteinuria had significantly higher periostin levels, compared with those with low proteinuria, periostin was considered the only independent predictor of proteinuria in Fabry patients.

“This correlation between [blood] periostin levels and proteinuria in Fabry patients is important both for the indicator of renal survival and a possible future treatment target,” the researchers wrote.