Origins of Common Kidney Disease Linked to Factors Beyond the Kidney

The origin of common kidney disease is most likely found outside the kidney, according to a recent study headed by Columbia University experts. The discovery of 16 additional sites in the genome linked to immunoglobulin A (IgA) nephropathy reinforces an earlier idea that the immune system plays a major role in driving the disease and points to new techniques for diagnosing and treating it (1^✔ ✔Trusted Source
Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy

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Uncovering the Cause of IgA Nephropathy

No targeted treatments for IgA nephropathy have been licensed, owing to a lack of understanding of the disease's fundamental cause. Identifying genes associated with an illness can reveal insights into its cause and assist the development of new treatments, but such studies require thousands of individuals. Those figures are difficult to reach in IgA nephropathy.

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Challenges in Diagnosis and Detection of IgA Nephropathy

Though prevalent in comparison to other types of immune-related kidney disease, IgA nephropathy is difficult to diagnose, and verified patients are difficult to detect. "The diagnosis requires a kidney biopsy, which is an invasive procedure that carries a lot of risks, so the diagnosis is frequently missed," explains Krzysztof Kiryluk, M.D., associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and main author of the study.

Kiryluk and his colleagues overcame the numbers challenge by assembling a large network of partners that included nephrologists, geneticists, and other scientists from four continents. Each participant gathered biopsied patients in their area and delivered blood samples to Kiryluk's Columbia team for DNA extraction and analysis.

The researchers compared DNA from IgA nephropathy sufferers to DNA from people who did not have the condition using samples from over 40,000 people. The 10-year study, which comprised over 200 scientists and clinicians from more than 100 institutions, is the largest ever on the genetics of IgA nephropathy.

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Genetic Discoveries and Potential Therapeutic Targets in IgA Nephropathy

Many of the novel genes discovered in the study are involved in the manufacture of IgA antibodies, lending credence to the concept that IgA level modulation is a critical role in the disease.

“That’s a very important finding because IgA nephropathy is considered to be a kidney disease, but it seems like its source is outside the kidney,” says Kiryluk. “We also developed a genetic risk profile that may help identify patients at highest risk of progression to kidney failure,” says Ali Gharavi, M.D., Jay Meltzer, M.D., Professor of Nephrology and Hypertension and co-leader of the study.

The researchers also identified proteins produced by the newly discovered genes that appear to be the greatest medication development targets. They also found two medications that have previously been examined for different illnesses and may have potential as IgA nephropathy therapies.

“A recent analysis found that drug targets backed by genetic studies are more likely to succeed,” Kiryluk says, “and we hope that pharmaceutical companies will start developing new therapies based on our findings.”

Reference:

1. Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy - (https://pubmed.ncbi.nlm.nih.gov/37337107/)

Source-Medindia