Hydrogen sulfide in renal physiology, disease and transplantation – The smell of renal protection

Koning, Anne M.; Frenay, Anne‐Roos S.; Leuvenink, Henri G. D.; Goor, Harry van

doi:10.1016/j.niox.2015.01.005

Cited by 70 publications

(54 citation statements)

References 144 publications

(221 reference statements)

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“…8 On the other hand, HCY metabolizes to generate CYS and hydrogen sulfide (H2S), which is a vasodilator involved in BP control. Given that hyperhomocysteinemia and dysregulation of H2S production have been reported in CKD, 27 and that hyperhomocysteinemia plays a role in HT, 28 our data support impaired HCY metabolism as possibly the major factor contributing to HT in patients with CKD. Notably, several components in the NO pathway and HCY metabolic pathway correlated with each other in this study.…”

Section: Discussionsupporting

confidence: 64%

Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease

Chien

Lin

Hsu

et al. 2015

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp (NO), a vasodilator, regulates endothelial function and blood pressure (BP). Our previous review indicated emerging evidence supporting that a deficiency of NO links endothelial dysfunction to CVD in pediatric CKD. 3 Because asymmetric dimethylarginine (ADMA) is an analog of L-arginine (ARG), the substrate for NO synthase (NOS), the ARG-to-ADMA ratio (AAR) represents NO bioavailability and maintains NO homeostasis. 4 Elevated plasma ADMA levels are observed in patients with hypertension (HT) as well as CKD. 5,6 Ambulatory BP monitoring (ABPM) has proven to be the best method of detecting abnormal BP and cardiovascular outcome in CKD. 7 Our recent reports showed that ARG metabolites in the NO pathway are interrelated and involved in abnormal ABPM profiles in children with CKD. 8,9 ADMA is synthesized by the ardiovascular disease (CVD) is a major cause of morbidity and mortality in children and adults with chronic kidney disease (CKD). 1 Unlike adults, young CKD patients rarely present with CV events. Thus assessment of CVD in childhood mainly relies on the characteristics of vascular phenotype. Less attention has been paid to evaluating subclinical CVD in the early stage of CKD in the pediatric population. It is noteworthy that CKD children with subclinical CVD are at risk of subsequent development of CVD in adulthood. Thus, identification of surrogate markers to detect subclinical CVD in early CKD children may aid in reducing the global burden of CKD.Deterioration in endothelial function and arterial stiffness are early events in the development of CVD. Background: Less attention has been paid to evaluating subclinical cardiovascular disease (CVD) in the early stage of pediatric chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) and arterial stiffness are the earliest detectable assessments of subclinical CVD. Asymmetric dimethylarginine (ADMA) is an analog of L-arginine (ARG) that inhibits nitric oxide (NO) production; thus the ARG-to-ADMA ratio (AAR) is an index of NO. Homocysteine (HCY) is a risk factor for CVD and it can be metabolized to L-cysteine (CYS). Given that HCY and ADMA/NO are closely linked and related to hypertension, we therefore investigated whether ARG and HCY metabolites, arterial stiffness parameters, ABPM profile, and left ventricular hypertrophy (LVH) are interrelated in children and adolescents with early CKD.

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Section: Discussionsupporting

confidence: 64%

Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease

Chien

Lin

Hsu

et al. 2015

Circ J

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“…The anti-apoptotic properties of H 2 S have been well-documented in many previous studies 20,21 . We examined the effects of H 2 S on renal apoptosis following obstruction via TUNEL staining and observed similar levels of apoptosis across all treatment groups.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 62%

GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy

et al. 2016

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“…H 2 S has been gaining more and more interest due to its significant renal protective effects in various forms of kidney diseases, including renal ischemia-reperfusion injury, diabetic nephropathy, obstructive kidney disease, hypertension related kidney disease, and so on [2, 3]. However, the role or the pattern of H 2 S in the progression of CKD has not been fully investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Substantial evidences suggest that endogenous H 2 S presents a vital effect on signal transduction and cell protection, playing a role in nerve conduction, blood pressure control, insulin release, renal blood flow regulation, and so on. A number of diseases have been proposed to associate with decreased H 2 S level, ranging from atherosclerosis, hypertension to myocardial infarction, and diabetes mellitus [2-5]. Nevertheless, the role of H 2 S in the pathogenesis of chronic kidney disease (CKD) has not been fully investigated.…”

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confidence: 99%

Low Plasma Hydrogen Sulfide Is Associated with Impaired Renal Function and Cardiac Dysfunction

et al. 2018

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Background: Chronic kidney disease (CKD) has been proposed to associate with decreased hydrogen sulfide (H₂S) level. Nevertheless, the role of H₂S in the pathogenesis of CKD has not been fully investigated. Our study aimed to investigate the plasma level of endogenous H₂S in patients with different stages of CKD, and to identify the role of H₂S in the progression of CKD and its relationship with cardiovascular diseases. Methods: A total of 157 non-dialysis CKD patients were recruited in our study, with 37 age- and sex-matched healthy individuals as control. Plasma concentration of H₂S was measured with spectrophotometry. Sulfhemoglobin, the integration of H₂S and hemoglobin, was characterized and measured by dual wavelength spectrophotometry. Serum levels of homocysteine (Hcy), cardiac troponin T (cTnT), and N-terminal pro B type natriuretic peptide were measured using automated analyzers. Conventional transthoracic echocardiography was performed and left ventricular ejection fraction (LVEF) was analyzed as a sensitive parameter of cardiac dysfunction. Results: The plasma H₂S level (μmol/L) in CKD patients was significantly lower than those in healthy controls (7.32 ± 4.02 vs. 14.11 ± 5.24 μmol/L, p < 0.01). Plasma H₂S level was positively associated with estimated glomerular filtration rate (eGFR; ρ = 0.577, p < 0.01) and negatively associated with plasma indoxyl sulfate concentration (ρ = –0.554, p < 0.01). The mRNA levels of cystathionine β-synthase and cystathionine γ-lyase, 2 catalytic enzymes of H₂S formation, were significantly lower in blood mononuclear cells of CKD patients with respect to controls; however, the mRNA level of 3-mercaptopyruvate sulfurtransferase, as another H₂S-producing enzyme, was significantly higher in CKD patients. The serum concentration of Hcy, acting as the substrate of H₂S synthetase, was higher in the CKD group (p < 0.01). Specifically, the content of serum Hcy in CKD stages 3–5 patients was significantly higher than that in CKD stages 1–2, indicating an increasing trend of serum Hcy with the decline of renal function. Examination of ultrasonic cardiogram revealed a negative correlation between plasma H₂S level and LVEF (ρ = –0.204, p < 0.05) in CKD patients. The H₂S level also correlated negatively with cTnT concentration (ρ = –0.249, p < 0.01). Conclusions: Plasma H₂S level decreased with the decline of eGFR, which may contribute to the cardiac dysfunction in CKD patients.

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Hydrogen sulfide in renal physiology, disease and transplantation – The smell of renal protection

Cited by 70 publications

References 144 publications

Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease

Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease

GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy

Low Plasma Hydrogen Sulfide Is Associated with Impaired Renal Function and Cardiac Dysfunction

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