A groundbreaking study led by researchers at Columbia University has identified 16 new genetic loci associated with immunoglobulin A (IgA) nephropathy, a common kidney disease.
The study, which has been published in Nature Genetics, supports previous hypotheses that the disease is driven by the immune system, not the kidney itself.
This insight could lead to new strategies for diagnosing and treating the disease.
Overcoming Obstacles to IgA Nephropathy Research
To date, no targeted treatments have been approved for IgA nephropathy, mainly because its underlying cause has been elusive.
While gene identification can offer insight into disease origins and direct drug development, achieving the patient numbers required for such studies has been a challenge for IgA nephropathy research.
Despite being relatively common compared to other immune-related kidney diseases, IgA nephropathy is difficult to diagnose.
Confirming the condition requires a kidney biopsy, an invasive and risky procedure, meaning many cases are likely missed, explains study lead Krzysztof Kiryluk, an associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.
To overcome these obstacles, Kiryluk and his team established an extensive network of collaborators spanning four continents.
Together, they collected blood samples from nearly 40,000 subjects, including biopsied patients with IgA nephropathy and those without the disease.
Unveiling New Genetic Clues and Potential Treatment Targets
The research, which took a decade to complete, represents the largest-ever study of IgA nephropathy’s genetic underpinnings.
The newly identified genes are predominantly involved in IgA antibody production, suggesting that regulation of IgA levels is central to the disease.
According to Kiryluk, this is a significant revelation. “IgA nephropathy is considered to be a kidney disease, but it seems like its source is outside the kidney.”
The team also developed a genetic risk profile that may help pinpoint patients most at risk of progressing to kidney failure, adds study co-leader Ali Gharavi.
Moreover, the study identified proteins produced by the newly discovered genes that could serve as promising targets for drug development.
Two drugs currently under investigation for other conditions were identified as potential treatments for IgA nephropathy.
Kiryluk is hopeful these findings will stimulate new therapeutic development. “A recent analysis found that drug targets backed by genetic studies are more likely to succeed,” he says.
“We hope that pharmaceutical companies will start developing new therapies based on our findings.”
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The study was published in Nature Genetics.
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