Researchers may have discovered a genetic explanation as to why some patients do not respond to hypertension treatment with thiazide diuretics. The study, appearing in the Journal of Clinical Investigation, was partially funded by the National Institutes of Health (NIH).

Paul Welling, MD, from the University of Maryland School of Medicine, and colleagues studied an animal model that was genetically engineered to mimic the effect of thiazides by inhibiting salt retention. After tracking for genetic changes in the animals, they discovered that almost 400 key genes changed their activity to assist in the regulation of salt in the kidneys; specifically, the genes acted on three different pathways related to salt retention.

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The scientists also identified a molecule that increases in the urine when the kidney is working to counteract thiazides. The researchers are currently investigating whether this biomarker could possibly help with early detection of thiazide ineffectiveness.

Building on this research, Dr. Welling states that drugs could be developed to affect the mechanisms by which the body counteracts thiazides for use as montherapy or adjunct treatment with thiazides for hypertension.

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