Hydrogen Sulfide-to-Thiosulfate Ratio Associated with Blood Pressure Abnormalities in Pediatric CKD

Identifying children with chronic kidney disease (CKD) at high risk of cardiovascular disease (CVD) and ensuring they receive appropriate treatment can prevent CVD events and mortality later in life. Hydrogen sulfide (H(2)S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H(2)S but is also a H(2)S donor. We examined whether H(2)S, thiosulfate, and their combined ratio have differential associations with CVD risk markers in 56 children and adolescents aged 6–18 years with CKD stages G1–G4. Up to two-thirds of CKD children showed higher BP load on 24 h ambulatory blood pressure monitoring (ABPM), even in the early stage. CKD children with ABPM abnormalities had a higher H(2)S-to-thiosulfate ratio, while H(2)S-related parameters were not affected by the severity of CKD. The H(2)S-to-thiosulfate ratio was positively correlated with 24 h systolic BP (SBP), nighttime SBP, and carotid artery intima-media thickness (cIMT). After adjusting for confounders, H(2)S was negatively associated with LV mass, thiosulfate was positively associated with 24-DBP, and the H(2)S-to-thiosulfate ratio was positively correlated with nighttime SBP and cIMT. Our data demonstrate differential associations in circulating H(2)S, thiosulfate, and their combined ratio with CVD risk in childhood CKD. Further studies are required to determine whether targeting the H(2)S signaling pathway can develop novel therapeutic strategies against CVD in this high-risk population.