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

ABSTRACT: 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 (H₂S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H₂S but is also a H₂S donor. We examined whether H₂S, 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 H₂S-to-thiosulfate ratio, while H₂S-related parameters were not affected by the severity of CKD. The H₂S-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, H₂S was negatively associated with LV mass, thiosulfate was positively associated with 24-DBP, and the H₂S-to-thiosulfate ratio was positively correlated with nighttime SBP and cIMT. Our data demonstrate differential associations in circulating H₂S, thiosulfate, and their combined ratio with CVD risk in childhood CKD. Further studies are required to determine whether targeting the H₂S signaling pathway can develop novel therapeutic strategies against CVD in this high-risk population.

SUBMITTER: Hsu CN

PROVIDER: S-EPMC9409977 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Hsu Chien-Ning CN Chen Wei-Ling WL Liao Wei-Ting WT Chang-Chien Guo-Ping GP Lin Sufan S Tain You-Lin YL

Journal of personalized medicine 20220729 8

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 (H2S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H2S but is also a H2S donor. We examined whether H2S, thiosulfate, and their combined ratio have differential associations ...[more]

PMID: 36013190

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Project description:Background and objectivesElevated BP load is part of the criteria for ambulatory hypertension in pediatric but not adult guidelines. Our objectives were to determine the prevalence of isolated BP load elevation and associated risk with adverse outcomes in children with CKD, and to ascertain whether BP load offers risk discrimination independently or in conjunction with mean ambulatory BPs.Design, setting, participants, & measurementsWe studied 533 children in the CKD in Children (CKiD) Study to determine the prevalence of normotension, isolated BP load elevation (≥25% of all readings elevated but mean BP normal), and ambulatory hypertension. We examined the association between these categories of BP control and adverse outcomes (left ventricular hypertrophy [LVH] or ESKD). We used c-statistics to determine risk discrimination for outcomes by BP load used either independently or in conjunction with other BP parameters.ResultsOverall, 23% of the cohort had isolated BP load elevation, but isolated BP load elevation was not statistically significantly associated with LVH in cross-section (odds ratio, 1.8; 95% CI, 0.8 to 4.2) or time to ESKD (hazard ratio, 1.2; 95% CI, 0.7 to 2.0). In unadjusted cross-sectional analysis, every 10% higher systolic BP load was associated with 1.1-times higher odds of LVH (95% CI, 1.0 to 1.3), but discrimination for LVH was poor (c=0.61). In unadjusted longitudinal analysis, every 10% higher systolic BP load was associated with a 1.2-times higher risk of ESKD (95% CI, 1.1 to 1.2), but discrimination for ESKD was also poor (c=0.60). After accounting for mean systolic BP, systolic BP load was not statistically significantly associated with either LVH or ESKD. Findings were similar with diastolic BP load.ConclusionsBP load does not provide additive value in discriminating outcomes when used independently or in conjunction with mean systolic BP in children with CKD.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_03_11_CPOD10130819.mp3.

Project description:Hydrogen sulfide (H2S) dilates isolated arteries, and knockout of the H2S-synthesizing enzyme cystathionine γ-lyase (CSE) increases blood pressure. However, the contributions of endogenously produced H2S to blood flow regulation in specific vascular beds are unknown. Published studies in isolated arteries show that CSE production of H2S influences vascular tone more in small mesenteric arteries than in renal arteries or the aorta. Therefore, the goal of this study was to evaluate H2S regulation of blood pressure, vascular resistance, and regional blood flows using chronically instrumented rats. We hypothesized that during whole animal CSE inhibition, vascular resistance would increase more in the mesenteric than the renal circulation. Under anesthesia, CSE inhibition [β-cyanoalanine (BCA), 30 mg/kg bolus + 5 mg·kg-1·min-1 for 20 min iv) rapidly increased mean arterial pressure (MAP) more than saline administration (%Δ: saline -1.4 ± 0.75 vs. BCA 7.1 ± 1.69, P < 0.05) but did not change resistance (MAP/flow) in either the mesenteric or renal circulation. In conscious rats, BCA infusion similarly increased MAP (%Δ: saline -0.8 ± 1.18 vs. BCA 8.2 ± 2.6, P < 0.05, n = 7) and significantly increased mesenteric resistance (saline 0.9 ± 3.1 vs. BCA 15.6 ± 6.5, P < 0.05, n = 12). The H2S donor Na2S (50 mg/kg) decreased blood pressure and mesenteric resistance ,but the fall in resistance was not significant. Inhibiting CSE for multiple days with dl-proparglycine (PAG, 50 mg·kg-1·min-1 iv bolus for 5 days) significantly increased vascular resistance in both mesenteric (ratio of day 1: saline 0.86 ± 0.033 vs. PAG 1.79 ± 0.38) and renal circulations (ratio of day 1: saline 1.26 ± 0.22 vs. 1.98 ± 0.14 PAG). These results support our hypothesis that CSE-derived H2S is an important regulator of blood pressure and vascular resistance in both mesenteric and renal circulations. Furthermore, inhalation anesthesia diminishes the effect of CSE inhibition on vascular tone.NEW & NOTEWORTHY These results suggest that CSE-derived H2S has a prominent role in regulating blood pressure and blood flow under physiological conditions, which may have been underestimated in prior studies in anesthetized subjects. Therefore, enhancing substrate availability or enzyme activity or dosing with H2S donors could be a novel therapeutic approach to treat cardiovascular diseases.

Dataset Information

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

Publications

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

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