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Genetic Pathway for Chronic Kidney Disease Revealed

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The University of Michigan Medical School led an international group of researchers in creating a molecular map of the body changes leading to chronic kidney disease.

Partly due to an aging and overweight population, chronic kidney disease  — a condition in which damaged kidneys cannot filter blood as well as healthy kidneys  — is one of the nation’s fastest growing chronic diseases.

“Addressing the initial mechanisms of CKD may be more beneficial and is good news for patients who could receive therapy earlier on for a variety of kidney diseases before they progress into CKD,” says Matthias Kretzler, M.D., a professor of internal medicine and bioinformatics and a nephrologist at the U-M Health System.

Diseases and infections that can damage kidneys and cause CKD include autoimmune disease like lupus leading to glomerulonephritis, polycystic kidney disease or kidney problems people are born with.

However, the most common causes of chronic kidney disease are diabetes and high blood pressure.  CKD affects over 13 percent of the United States population, about 26 million people.

Using combined genetic and clinical data, Kretzler, U-M’s Sebastian Martini, M.D., and colleagues revealed a network of shared genetic pathways associated with CKD. 

This unique methodology helped to describe what the key molecular drivers of CKD are, what CKD-causing diseases were most closely related and to understand specific molecular mechanisms causing the disease to progress or worsen in different patients.

The CKDGen consortium, European Renal cDNA Bank-Kroener-Fresenius Biopsy Bank, and the Clinical Phenotyping Resource and Biobank core contributed to the study published online ahead of print in the Journal of the American Society of Nephrology.

"The study highlighted why understanding the way different diseases share the same molecular mechanism is important for treatment," says Martini, a systems biologist at the U-M Medical School.

Current treatments can decrease the rate at which CKD worsens and contributes to other health problems, but they do not prevent progression.  Once kidneys fail, people need dialysis or a kidney transplant to live.