A Toxic Environment for Kidneys

Chronic kidney disease has been on the rise for two decades and no one knows why. According to new research from HHMI investigator Friedhelm Hildebrandt, the problem could be faulty repair of DNA that’s been damaged by environmental toxins.

To find the causes of kidney disease, Hildebrandt and his team at the University of Michigan Medical School looked at the exomes—DNA regions that code for proteins—of 50 families with childhood kidney disorders. They discovered mutations in four genes associated with chronic kidney disease: FAN1MRE11ZNF423, and CEP164. Surprisingly, all four genes control DNA repair. The group reported its findings in the August 3, 2012, issue of Cell and the August 2012 issue of Nature Genetics.

The DNA repair system fixes errors in the genetic code caused by slipups during DNA replication or by genotoxins—environmental factors that damage genetic material. When the system fails, mutations remain and the cells cannot function properly.

While the connection between DNA repair and kidney failure is not clear, the kidneys may be particularly susceptible to DNA degeneration caused by genotoxins because their job is to eliminate many toxins from the body. Hildebrandt believes that the discovery of this disease mechanism will help in diagnosing kidney failure and offers clues for developing treatments.

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Boston Children’s Hospital

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