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Changes in gene expression profiles in chronic kidney disease patients treated with tetrahydrobiopterin versus placebo: a randomized controlled trial (912.11)

Chronic kidney disease (CKD) patients are at significantly higher risk of cardiovascular mortality. One major contributing factor is decreased nitric oxide (NO) bioavailability, which leads to endothelial dysfunction and sympathetic nervous system (SNS) overactivity. Tetrahydrobiopterin (BH4) is a cofactor for endothelial NO synthase activity that has been shown to improve NO bioavailability and endothelial function in animal models of CKD; however, BH4 treatment had never before been tested in humans with CKD. We hypothesized that BH4 treatment alters gene expression profiles in CKD; particularly, the RNA activity of genes involved in the regulation of NO and SNS activity. In a randomized, double‐masked, placebo‐controlled trial, we randomized 36 hypertensive CKD patients to 12 weeks of: a) BH4 200 mg twice daily + folic acid 1 mg daily; versus b) identical placebo twice daily + folic acid 1 mg daily. Physiologic measures and blood collected in tempus tubes were obtained before and after treatment. Total RNA will be extracted, and gene expression profiling will be performed using the Illumina HT12 BeadChip technology at the Emory Integrative Genomics Core laboratory. We anticipate that expression of candidate genes involved in NO and SNS regulation may be altered with time in CKD patients treated with BH4.