Jackson researchers find genetic links to condition that causes kidney damage in diabetics

Date: February 18, 2010
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Bar Harbor, Maine -- Albuminuria, or proteinuria is a condition in which urine contains an abnormal amount of the protein albumin, and is a sign of kidney damage resulting from diabetes or other medical conditions. A Jackson Laboratory research team led by Research Scientist Ron Korstanje, Ph.D., has discovered two genes that are associated with albuminuria in both aging mice and human patients with diabetic kidney disease.

Albumin is the primary protein in the blood, an essential factor in warding off infection, clotting and circulation. Healthy kidneys filter out waste products; like most proteins, albumin is too big to pass through the kidneys' filters, called glomeruli, and is left in the blood. But when diabetes or other disease damages the glomeruli, proteins from the blood leak into the urine and waste products build up in the blood, which can ultimately lead to kidney failure.

According to Dr. Korstanje, even aging itself can cause albuminuria, so he and his team looked for signs of the condition in mice of different ages. They identified nine genes in which variations were associated with mice having the highest albumin-to-creatinine ratios, a measure of urinary albumin excretion.

"We then 'looked up' these nine genes in genome-wide association scans for human type 1 diabetes patients with diabetic nephropathy, in a collaboration with Dr. Krolewski from Harvard Medical School's Joslin Diabetes Center," Dr. Korstanje explains. "We found that two of the nine were significantly associated with kidney disease and were consistent regardless of sex. This suggests that common underlying genes predispose to kidney disease in mice and humans."

The findings offer new clues to addressing chronic kidney disease, which affects as many as 23 million Americans, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Chronic kidney disease can lead to end-stage renal disease, in which the kidneys fail completely, necessitating either a kidney transplant or regular blood-cleansing treatments called dialysis. Diabetes is the leading cause of end-stage renal disease, followed by hypertension and other kidney and urologic diseases.

The researchers reported their findings in the February edition of the journal Kidney International, published by Nature. In another paper published this month in the Journal of the American Society of Nephrology, with colleagues at the Joslin Diabetes Center and the Medical College of Wisconsin, Dr. Korstanje showed that comparative genetic approaches across species -- humans, mice and rats -- can accelerate the discovery of genes associated with kidney disease, which can then be investigated in experiments with the animal models.

The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a facility in Sacramento, Calif. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community.

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Tsaih et al.: Genetic analysis of albuminuria in aging mice and concordance with loci for human diabetic nephropathy found in a genome-wide association scan. Kidney International (2010) 77, 201Ð210; doi:10.1038/ki.2009.434, February 1, 2010.

Garrett et al.: Integrating human and rodent data to identify the genetic factors involved in chronic kidney disease. Journal of the American Society of Nephrology, 21: 398Ð405, 2010. doi: 10.1681/ASN.2009080881, February 2010.

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