Two independent studies published in the journal Molecular Genetics and Metabolism and presented at the 14th Annual WORLDSymposium in San Diego, California, have discovered possible biomarkers to diagnose heart and kidney disorders in Fabry disease.
One study, “Collagen type I synthesis biomarkers predict the progression of Fabry disease cardiomyopathy,” addressed Fabry disease cardiomyopathy — a condition characterized by thickened and scarring of the heart muscle.
Fibrosis in the myocardium, the muscular center layer of the heart, is irreversible and affects a patient’s prognosis. Therefore, discovering biomarkers to enable disease development and prediction can prove crucial for these patients.
Researchers addressed the validity of type I collagen synthesis (PICP) and degradation (MMP-1) biomarkers for fibrosis and left ventricular (LV) hyperthrophy in Fabry patients.
Type I collagen is the most abundant type of collagen and a key structural component of several tissues, including cardiac tissue.
A total of 60 patients were followed for 24 months. All patients exhibited cardiac abnormalities and were classified into two groups based on their heart’s left ventricular mass (LVM) and end-diastolic pressure (LVEDP).
Results showed no changes in PICP and MMP-1 biomarkers during follow-up.
Patients with left ventricular end-diastolic pressure had lower concentrations of serum MMP-1 at baseline. There was also a significant correlation between PICP variation and left ventricular mass changes, with PICP levels either increasing or decreasing in accordance with patients’ left ventricular mass oscillations.
These results suggest that collagen type I synthesis has a good prognostic value as a biomarker for Fabry disease.
The authors also believe that blocking enzymes involved in its breakdown may prove crucial for collagen accumulation in the heart, and is related to the risk of progressive diastolic dysfunction.
The second study, “Tubular dysfunction biomarkers in Fabry disease: better than albuminuria to identify patients at risk of nephropathy progression,” focused on kidney disease associated with Fabry disease (nephropathy).
The presence of albumin protein in urine, called albuminuria, influences disease nephropathy, but how much of an influence is not well established, with different studies showing conflicting results.
The team conducted a multi-center study in 78 Fabry disease patients who were followed for two years. The levels of a biomarker of kidney tubular dysfunction, called uNAG, were compared to those of albuminuria — the reference standard — to identify decline in glomerular filtration rate which serves as an indicator of kidney function.
Results revealed the glomerular filtration rate declined in 28% of patients in the study. Albuminuria levels remained stable whereas those of uNAG increased.
Patients who showed a decline in the glomerular filtration rate had higher albuminuria and uNAG levels at baseline. But a detailed analysis showed that only uNAG levels correlated with glomerular filtration rate changes.
Researchers believe these findings suggest uNAG outperforms albuminuria “as a prognostic biomarker, clearly identifying patients at increased risk of progressive nephropathy.”