A study suggests that source of common kidney disease may originate from outside the kidney

The cause of a common kidney disease likely lies outside the kidney, according to a new study led by Columbia University researchers. The study, which uncovered 16 new locations in the genome linked to immunoglobulin A (IgA) nephropathy, confirms an earlier hypothesis that the immune system has an important role in driving the disease and points toward new strategies for detecting and treating it.

No targeted treatments have been approved to treat IgA nephropathy, largely because the underlying cause of the disease has not been well understood. Identifying genes linked to disease can provide clues to its source and guide the development of new drugs, but thousands of patients are needed for such studies. For IgA nephropathy, those numbers are difficult to achieve.

Though common compared to other forms of kidney disease related to the immune system, IgA nephropathy is hard to diagnose, and confirmed patients are difficult to find.

With samples from almost 40,000 subjects, the researchers compared DNA from IgA nephropathy cases to DNA from people who do not have the disease. The study, which took 10 years to complete and involved nearly 200 scientists and clinicians at more than 100 institutions, is the largest ever of the genetics of IgA nephropathy

Many of the new genes identified in the study are involved in the production of IgA antibodies, reinforcing the idea that regulation of IgA levels is the key factor behind the disease.

Reference: Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy, Nature Genetics, DOI 10.1038/s41588-023-01422-x