Genetic marker may help predict success of kidney transplants

PUBLIC RELEASE DATE:

1-Dec-2014

Contact: David Slotnick newsmedia@mssm.edu The Mount Sinai Hospital / Mount Sinai School of Medicine @mountsinainyc

(NEW YORK - December 1, 2014) Kidneys donated by people born with a small variation in the code of a key gene may be more likely, once in the transplant recipient, to accumulate scar tissue that contributes to kidney failure, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published today in the Journal of Clinical Investigation.

If further studies prove the variation to cause fibrosis (scarring) in the kidneys of transplant recipients, researchers may be able to use it to better screen potential donors and improve transplant outcomes. Furthermore, uncovering the protein pathways that trigger kidney fibrosis may help researchers design drugs that prevent this disease process in kidney transplant recipients, and perhaps in all patients with chronic kidney disease.

"It is critically important that we identify new therapeutic targets to prevent scarring within transplanted kidneys, and our study has linked a genetic marker, and related protein pathways, to poor outcomes in kidney transplantation," said Barbara Murphy, MD, Chair, Department of Medicine, Murray M. Rosenberg Professor of Medicine (Nephrology) and Dean for Clinical Integration and Population Health at the Icahn School of Medicine at Mount Sinai. "Drug designers may soon be able to target these mechanisms."

A commonly used study type in years, the genome-wide association study (GWAS) looks at differences at many points in the genetic code to see if, across a population, any given variation in the genetic code is found more often in those with a given trait; in the case of the current study, with increased fibrosis in recipients of donated kidneys.

Even the smallest genetic variations, called single nucleotide polymorphisms (SNPs), can have a major impact on a trait by swapping just one of 3.2 billion "letters" making up the human DNA code. The current study found a statistically significant association between SNP identified as rs17319721 in the gene SHROOM3 and progressive kidney scarring (fibrosis) and function loss in a group of kidney donors, mostly of European descent. In many cases, certain SNPs will be more common in families or ethnic groups.

The kidneys filter the blood to remove extra blood sugar and waste products that trickle down the kidney tubes to become urine, while re-absorbing key nutrients. The build-up of scar tissue in these delicate structures over time interferes with proper renal function.

Chronic kidney disease already affects 10 percent of US adults and its prevalence is increasing. Along with leading to kidney failure in many cases, chronic kidney disease increases the risk of cardiovascular disease. Fibrosis in kidney tubules is a common pathogenic process for many types of chronic kidney disease, and a central part of chronic disease in donated kidneys (chronic allograft nephropathy, or CAN).

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Genetic marker may help predict success of kidney transplants