L-Arginine/NO Pathway Is Altered in Children with Haemolytic-Uraemic Syndrome (HUS)

Kanzelmeyer, Nele; Pape, Lars; Chobanyan-Jürgens, Kristine; Tsikas, Dimitrios; Hartmann, Hans; Fuchs, Anne-Jule; Vaske, Bernhard; Haubitz, Marion; Jordan, Jens; Lücke, Thomas

doi:10.1155/2014/203512

Cited by 9 publications

(11 citation statements)

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“…Our groups have investigated this pathway in healthy children and in children with renal and metabolic diseases (Lücke et al 2006a, b;Kanzelmeyer et al 2012Kanzelmeyer et al , 2014Chobanyan-Jürgens et al 2012a). The L-Arg/NO pathway in children differs from that in adults.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, the role of ADMA and other members of the L-Arg/NO pathway in children with renal and metabolic diseases has been investigated (Goonasekera et al 1997;Lücke et al 2006aLücke et al , b, 2007Lücke et al , 2008Kanzelmeyer et al 2012Kanzelmeyer et al , 2014. Elevated ADMA levels were found for example in children with hypertension (Goonasekera et al 1997) and citrullinemia (Lücke et al 2006a).…”

Section: Introductionmentioning

confidence: 99%

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The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

et al. 2015

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The L-arginine/nitric oxide (L-Arg/NO) pathway regulates endothelial function and may play an important role in the pathogenesis of Duchenne muscular dystrophy (DMD). Yet, this pathway is poorly investigated in children suffering from DMD. Endothelial dysfunction can affect the perfusion of contracting muscles, thus leading to ischemia and hypoxia. In the present study, we tested the hypothesis that reduced NO production due to elevated synthesis of N (G),N (G)-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA), an endogenous inhibitor of NO synthesis, is a possible pathophysiological mechanism for progressive intramuscular muscle ischemia and disturbed endothelial function in children with DMD. Given the possible antagonistic action of homoarginine (hArg) on ADMA, we also analyzed this amino acid. We investigated 55 male patients with DMD and 54 healthy male controls (HC; aged 11.9 ± 4.8 vs. 11.1 ± 4.9 years, mean ± SD). Urinary creatinine and metabolites of the L-Arg/NO pathway were measured in plasma and urine by GC-MS or GC-MS/MS. Urine levels of ADMA and its major urinary metabolite dimethylamine (DMA), nitrite and nitrate (P < 0.001 for all) and hArg (P = 0.002) were significantly higher in DMD patients compared to HC, while the urinary DMA/ADMA molar ratio was lower (P = 0.002). In plasma, nitrate (P < 0.001), hArg (P = 0.002) and the hArg/ADMA ratio (P < 0.001) were lower in DMD than in HC. In plasma, ADMA (631 ± 119 vs. 595 ± 129 nM, P = 0.149), arginine and nitrite did not differ between DMD and HC. In DMD, positive correlations between ADMA, DMA or nitrate excretion and the stage of disease (according to Vignos and Thompson) were found. In DMD patients on steroid medication, lower concentrations of ADMA in plasma, and of DMA, ADMA, nitrate and hArg in urine were observed compared to non-treated patients. The L-Arg/NO pathway is impaired in DMD patients, with the disease progression being clinically negatively correlated with the extent of impairment. One of the underlying mechanisms in DMD may involve insufficient antagonism of ADMA by hArg. Steroids, but not creatine supplementation, seems to improve the L-Arg/NO pathway in DMD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

et al. 2015

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“…In a small group of children with haemolytic-uraemic syndrome (HUS), the creatinine-corrected excretion rates were 13.7 µmol/mmol for DMA and 3.3 µmol/mmol for ADMA, corresponding to a low DMA/ADMA molar ratio of about 4 ( Table 1 ) [ 42 ]. In pediatric homocystinuria, high creatinine-corrected excretion rates of DMA (62.2 µmol/mmol) and ADMA (8.1 µmol/mmol) were measured, resulting in a rather “normal” DMA/ADMA molar ratio of 7.7 ( Table 1 ) [ 43 ].…”

Section: Urinary Dma and Adma In Children Adolescents And Adults mentioning

confidence: 99%

Urinary Dimethylamine (DMA) and Its Precursor Asymmetric Dimethylarginine (ADMA) in Clinical Medicine, in the Context of Nitric Oxide (NO) and Beyond

Tsikas

2020

JCM

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Asymmetric protein-arginine dimethylation is a major post-translational modification (PTM) catalyzed by protein-arginine methyltransferase (PRMT). Regular proteolysis releases asymmetric dimethylarginine (ADMA). Of the daily produced ADMA, about 10% are excreted unchanged in the urine. The remaining 90% are hydrolyzed by dimethylarginine dimethylaminohydrolase (DDAH) to L-citrulline and dimethylamine (DMA), which is readily excreted in the urine. The PRMT/DDAH pathway is almost the exclusive origin of urinary ADMA and the major source of urinary DMA. Dietary fish and seafood represent additional abundant sources of urinary DMA. The present article provides an overview of urinary ADMA and DMA reported thus far in epidemiological, clinical and pharmacological studies, in connection with the L-arginine/nitric oxide (NO) pathway and beyond, in neonates, children and adolescents, young and elderly subjects, males and females. Discussed diseases mainly include those relating to the renal and cardiovascular systems such as peripheral arterial occlusive disease, coronary artery disease, chronic kidney disease, rheumatoid arthritis, Becker muscular disease, Duchenne muscular disease (DMD), attention deficit hyperactivity disorder (ADHD), and type I diabetes. Under standardized conditions involving the abstinence of DMA-rich fresh and canned fish and seafood, urinary DMA and ADMA are useful as measures of whole-body asymmetric arginine-dimethylation in health and disease. The creatinine-corrected excretion rates of DMA range from 10 to 80 µmol/mmol in adults and up to 400 µmol/mmol in children and adolescents. The creatinine-corrected excretion rates of ADMA are on average 10 times lower. In general, diseases are associated with higher urinary DMA and ADMA excretion rates, and pharmacological treatment, such as with steroids and creatine (in DMD), decreases their excretion rates, which may be accompanied by a decreased urinary excretion of nitrate, the major metabolite of NO. In healthy subjects and in rheumatoid arthritis patients, the urinary excretion rate of DMA correlates positively with the excretion rate of dihydroxyphenylglycol (DHPG), the major urinary catecholamines metabolite, suggesting a potential interplay in the PRMT/DDAH/NO pathway.

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“…One study evaluated ADMA in pediatric hemolytic uremic syndrome (HUS), a frequent cause of acute renal failure in childhood. In 12 children with HUS who received PD, the mean ADMA levels were measured by the GC-MS/MS method to be 0.67 µM/L for HUS and 0.75 µM/L for controls [71].…”

Section: Adma As a Biomarker In Pediatric Kidney Diseasementioning

confidence: 99%

Asymmetric Dimethylarginine (ADMA) in Pediatric Renal Diseases: From Pathophysiological Phenomenon to Clinical Biomarker and Beyond

Hsu

Tain

2021

Children

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Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) synthase inhibitor, inhibits NO synthesis and contributes to the pathogenesis of many human diseases. In adults, ADMA has been identified as a biomarker for chronic kidney disease (CKD) progression and cardiovascular risk. However, little attention is given to translating the adult experience into the pediatric clinical setting. In the current review, we summarize circulating and urinary ADMA reported thus far in clinical studies relating to kidney disease in children and adolescents, as well as systematize the knowledge on pathophysiological role of ADMA in the kidneys. The aim of this review is also to show the various analytical methods for measuring ADMA and the issues tht need to be addressed before transforming to clinical practice in pediatric medicine. The last task is to suggest that ADMA may not only be suitable as a diagnostic or prognostic biomarker, but also a promising therapeutic strategy to treat pediatric kidney disease in the future.

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L-Arginine/NO Pathway Is Altered in Children with Haemolytic-Uraemic Syndrome (HUS)

Cited by 9 publications

References 51 publications

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

Urinary Dimethylamine (DMA) and Its Precursor Asymmetric Dimethylarginine (ADMA) in Clinical Medicine, in the Context of Nitric Oxide (NO) and Beyond

Asymmetric Dimethylarginine (ADMA) in Pediatric Renal Diseases: From Pathophysiological Phenomenon to Clinical Biomarker and Beyond

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