A significant reduction in the BH4/BH2 ratio was observed in patients with CKD-5 compared with the non-CKD control and CKD-3 participants (control 1.40 nM/nM (1.10–2.0) vs. CKD-3 1.55 nM/nM (1.10–2.32) vs. CKD-5 0.50 nM/nM (0.25–1.0); Figure 2A), which suggests a decreased conversion of BH2 to BH4 or reduced activity of dihydrofolate reductase. This evidence concerns the gene DHFR and chronic kidney disease.