Cause for nephrotic syndrome found

Recessive mutations in a gene called phospholipase C epsilon, or PLCE1, have been identified as the cause of a kidney disease called nephrotic syndrome. Untreated nephrotic syndrome progresses about 50% of the time to end-stage kidney disease and renal failure. Some types of nephrotic syndrome can be treated with steroids or other drugs, but some forms are steroid-resistant.

U-M scientists used DNA from 12 children with the disease. All 12 had inherited recessive mutations in PLCE1 from both parents. None of the seven different PLCE1 mutations were present in the 138 control subjects in the study. All 12 children developed symptoms of nephrotic syndrome before age four. Five children progressed to end-stage renal disease before age five. But surprisingly, two children who received early treatment with steroids or cyclosporin A were still alive and healthy, with no symptoms of the disease.

Surprised by these results, the researchers tracked down their physicians – one in Israel and one in Turkey – to confirm that the information was correct. “These children were very fortunate,” said Friedhelm Hildebrandt, the U-M's Frederick G L Huetwell professor for the cure and prevention of birth defects. “Their physicians told us they decided there was nothing to lose by trying a course of treatment. Based on this information, we now think that there may be a critical time window during which treatment can overcome the development defects caused by PLCE1's loss of function.”

Although the scientists stressed that more research was needed, and steroid treatment was not going to be a golden bullet, the results give hope for a future treatment for the disease.