Bromide Worsened Alport Kidney Disease in Mice Study, Countering Previous Beliefs of Benefits
Bromide supplementation might be harmful to Alport syndrome patients if the findings of a study in mice translate into human settings. Researchers at Kumamoto University in Japan found that giving bromide to Alport mice worsened their disease.
The results countered an earlier study noting that bromide is a trace element required for normal kidney function, and suggested that it could have adverse effects when applied to Alport kidney disease.
The study, “Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome,” was published in the journal Plos One.
The 2014 study had examined the role of bromide in fruit flies, and showed that the trace element was required for kidney basement membrane formation. Giving the flies bromide supplementation had restored the flaws in the basement membrane.
Back then, researchers suggested that bromide supplementation might improve kidney conditions. Because bromide-containing drugs already are available for the treatment of epilepsy, researchers thought they might be repurposed for treating kidney disease.
Because Alport syndrome (AS) is a disease in which the kidney basement membrane is disrupted, the Japanese research team thought that the approach might lessen kidney abnormalities seen with the disease.
Using a mouse model of X-linked Alport syndrome, researchers delivered 75 mg/kg or 250 mg/kg of sodium bromide to the mice daily for 16 weeks. Control animals were given sodium chloride, or common salt.
Researchers noted no impact from the lower dose of the treatment. But animals given the higher dose developed more severe disease than Alport mice given a salt solution. These mice had worse progression of protein leakage into the urine and higher serum creatinine levels, a sign of damaged renal function.
When examining their kidneys under the microscope, researchers noted that damage to the glomeruli — the kidney’s filtering units — was worse in the mice given the higher bromide dose. These animals had more glomeruli with severe damage and very few unaffected ones.
Further analyses showed that the bromide had also triggered inflammation, with higher numbers of infiltrating inflammatory cells and mediators. Fibrosis also became worse.
These effects were not seen in normal mice exposed to the same bromide supplementation regimen.
The team suggested that bromide might be accumulated in Alport kidneys.
“These findings suggest that Br– [bromide] supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM [glomerular basement membrane] diseases such as AS,” the authors concluded.