ROCHESTER, Minn.-- Mayo Clinic researchers have used pharmacogenomics to develop a test and treatment for an inherited kidney disorder that can cause organ failure in children and young adults. The findings appear in the current issue of the journal Kidney International ( http://www.blackwell-synergy.com/links/doi/10.1111/j.1523-1755.2005.00267.x/full/). Pharmacogenomics tailors treatment to an individual's genetic makeup to maximize the therapeutic response.
Early diagnosis is important, as the condition -- type I primary hyperoxaluria -- if not treated early and correctly, can cause kidney stones or kidney failure and necessitate a transplant. The researchers discovered that a genetic mutation allows certain kidney stone patients -- many of them children -- to benefit from vitamin B6, and have used the finding to develop a genetic test to predict which patients are best suited for this treatment.
In discovering the link between a specific mutation and vitamin B6 responsiveness, the Mayo Clinic researchers can now use a genetic test for guiding treatment to maximize the probability of swift, successful treatment for select cases of type I primary hyperoxaluria. The disease is uncommon, but if left undiagnosed and untreated, at least half of those affected will suffer kidney failure. Patients most often develop the first symptoms -- usually kidney stones -- during infancy or childhood. However, the disorder may go unrecognized until age 30 to 40. In some cases the first symptom is kidney failure.
The gene defect responsible for the disorder disrupts production of a key enzyme located in the liver, and this enzymatic deficit then allows the liver to produce too much oxalate, which is excreted in the urine. High concentrations of oxalate in the urine can cause kidney stones and injury to the kidney, leading to kidney failure.
"While there are still questions to resolve -- such as determining the most effective dose, and the safety of vitamin B6 if very high doses are used -- our demonstration of the relationship between a specific mutation and vitamin B6 responsiveness does open the door to informed use of this valuable agent in the treatment of type I primary hyperoxaluria," says Carla Monico, M.D., Mayo Clinic nephrologist and lead researcher on the study. The research team will now try to determine the most effective doses and evaluate benefits of this approach long term.
The Problem and the Mayo solution
Doctors have known for more than 40 years that vitamin B6 therapy can effectively lower the dangerous oxalate levels in urine of patients with type I primary hyperoxaluria. But the clinical usefulness of that information has been limited by the fact that vitamin B6's therapeutic effect only occurs in about 50 percent of patients. No one knew why.
Mayo Clinic researchers now have both an explanation for the varied response and a way to predict who will respond to vitamin B6 therapy. By studying 23 patients' genetic profiles and their response rates to various dose levels of vitamin B6, the researchers found that a specific gene mutation governs how a patient will respond to vitamin B6. As a result, researchers can now use a genetic test to identify patients best suited for this therapy.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.
No one can make you feel inferior without your consent.
~ Eleanor Roosevelt