Levels of a protein called fibronectin in urine of Bardet-Biedl syndrome (BBS) patients correlate with renal dysfunction, a study shows, suggesting that fibronectin could be a potential biomarker for BBS patients at risk of kidney failure.
The study, “Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome” was published in the journal Kidney & Blood Pressure Research.
BBS is a rare genetic disorder whose symptoms include obesity, vision loss, and intellectual disability. Kidney dysfunction is also a major clinical feature of BBS, and can lead to life-threatening situations.
Errors in more than 20 genes have been linked with BBS, but scientists have not yet uncovered the link between genetic errors and systemic related renal disease in BBS.
Furthermore, the degree of kidney dysfunction among BBS patients is highly variable, with some patients showing mild impairments while others develop kidney failure, also called end-stage renal disease. Moreover, the molecular mechanism underlying kidney dysfunction, as well as potential risk factors, remains poorly understood.
“To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting,” researchers said.
To address this, researchers in Naples, Italy, hypothesized that by analyzing the protein content of BSS patients’ urine, they could find new markers for early detection of kidney issues.
The team collected urine samples from 14 BSS patients (seven females and seven males) ages 19-43, and 20 age- and gender-matched healthy controls. Urine was collected after 12 hours (overnight) fasting, and submitted to protein extraction and a proteomic analysis.
To assess the severity of kidney disease, patients underwent biochemical analysis and kidney ultrasound. Researchers also measured patients’ mean annual decline in glomerular filtration rate (eGFR), a test used to check how well the kidneys are working. Low eGFR levels are a sign of kidney disease.
Patients were followed up upon for a mean period of four years.
The proteomics analysis showed that the urine proteome of BSS patients differed from that of controls. Specifically, 42 proteins showed abnormal levels in both male and female BBS patients.
By analyzing the proteins altered in BBS patients’ urine, researchers found that three proteins — fibronectin, CD44, and lysosomal alpha-glucosidase — were significantly correlated with eGFR score.
The analysis also showed that fibronectin in particular was significantly correlated with the mean annual decline of eGFR, a finding that “further confirms the importance of this protein as a marker of kidney disease,” researchers said.
Overall, “our data indicate the potentiality of urine proteomics in the discovery of early markers of eGFR decline in BBS,” researchers stated, although “larger prospective studies are required to confirm these findings.”
“The possibility to assess the risk to develop chronic kidney disease will impact the management of BBS patients, enabling to start preventive strategies in time,” the team concluded.