Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS)

Lücke, Thomas; Kanzelmeyer, Nele; Chobanyan, Kristine; Tsikas, Dimitrios; Franke, Doris; Kemper, Markus J.; Ehrich, J. H. H.; Das, Anibh M.

doi:10.1093/ndt/gfm761

Cited by 24 publications

(27 citation statements)

References 27 publications

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“…In contrast to many studies [1,11,[32][33][34][35], the outcomes of the current study show that in the relapse phase, ADMA was negatively correlated with cholesterolemia and triglyceridemia. There are several explanations for these controversial results.…”

Section: Discussioncontrasting

confidence: 99%

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

Hyla-Klekot¹,

Bryniarski²,

Pulcer³

et al. 2015

Adv Clin Exp Med

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Background. Nephrotic syndrome in children is commonly associated with dyslipidemia, which is considered a risk factor for endothelial dysfunction and atherosclerosis. Recently new markers of endothelial dysfunction, such as asymmetric dimethylarginine (ADMA), have gained importance. Another L-arginine derivative -symmetric dimethylarginine (SDMA) -may reflect the glomerular filtration rate (GFR). Objectives. The main aim of this study was to assess ADMA as a marker of atherosclerosis. Secondly, SDMA was examined for GFR assessment. Material and Methods. The study involved 32 children with nephrotic syndrome. Several parameters were examined in the remission and relapse phases of nephrotic syndrome, including ADMA, SDMA, cholesterol, triglycerides and GFR. Results. In the relapse phase there was a negative correlation between ADMA and lipids (cholesterol and triglycerides). In both phases SDMA was negatively correlated with GFR. Conclusions. The role of ADMA as a marker for endothelial dysfunction is not significant. SDMA may be utilized to monitor GFR in children with nephrotic syndrome (Adv Clin Exp Med 2015, 24, 2, 307-313).

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Section: Discussioncontrasting

confidence: 99%

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

Hyla-Klekot¹,

Bryniarski²,

Pulcer³

et al. 2015

Adv Clin Exp Med

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“…High ADMA levels have been found in adults with type 1 diabetes mellitus (T1DM) compared to healthy controls (Altinova et al 2007;Marcovecchio et al 2011). In previous studies, we reported on developmental changes in the Arg/NO pathway from infancy to adulthood, showing a decrease in plasma ADMA levels with age (Lücke et al 2007), as well as in metabolic diseases (Lücke et al 2006(Lücke et al , 2008ChobanyanJürgens et al 2012a;Kanzelmeyer et al 2012) (Fig. 1).…”

Section: Introductionmentioning

confidence: 88%

“…However, others reported even a significant decrease in circulating ADMA levels in young diabetics with a mean age of 12 years and mean HbA 1c of 8.2 % (Huemer et al 2011). Comparably higher ADMA concentrations were also found in children with renal diseases (Lücke et al 2008;Brooks et al 2009;Wang et al 2007), in hypercholesterolemia (Hasanoğlu et al 2011), as well as in arterial hypertension (Sladowska-Kozłowska et al 2012) and pulmonary hypertension (Sanli et al 2012). The children examined in the present study did not have elevated concentrations of creatinine, cholesterol and triglycerides; also, they had no microalbuminuria, arterial hypertension or pulmonary hypertension (Table 1).…”

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 95%

“…Other important factors to be considered in the discussion are the influence of renal function, glucose or insulin on the metabolism and elimination of ADMA (Vallance et al 1992;Cighetti et al 2009;Lajer et al 2009;Tarnow et al 2004). Like in adults, the circulating ADMA concentration has been shown to be elevated in children when renal function was impaired (Wang et al 2007;Lücke et al 2008;Brooks et al 2009). …”

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 99%

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The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

et al. 2015

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High circulating levels of asymmetric dimethylarginine (ADMA) and low circulating levels of homoarginine (hArg) are known cardiovascular risk factors in adults. While in adults with type 1 diabetes mellitus (T1DM) circulating ADMA is significantly elevated, in children and adolescents the reported ADMA data are contradictory. In 102 children with T1DM and 95 healthy controls (HC) serving as controls, we investigated the L-arginine (Arg)/nitric oxide (NO) pathway. Children with T1DM were divided into two groups, i.e., in children with newly diagnosed diabetes mellitus [T1DM-ND; n = 10; age, 8.8 (4.4-11.2) years; HbA1c, 13 (8.9-13.9) %] and in those with long-term treatment [T1DM-T; n = 92; age, 12.5 (10.5-15.4) years; HbA1c, 8.0 (7.2-8.6) %]. The age of the HC was 11.3 (8-13.3) years. Amino acids and NO metabolites of the Arg/NO pathway, creatinine and the oxidative stress biomarker malondialdehyde (MDA) were measured by GC-MS or GC-MS/MS. Plasma hArg, ADMA and the hArg/ADMA molar ratio did not differ between the T1DM and HC groups. There was a significant difference between T1DM-T and HC with regard to plasma nitrite [0.53 (0.48-0.61) vs 2.05 (0.86-2.36) µM, P < 0.0001] as well as to urinary nitrite [0.09 (0.06-0.17) vs 0.22 (0.13-0.37) μmol/mmol creatinine, P < 0.0001]. Plasma, but not urinary nitrite, differed between T1DM-ND and HC [0.55 (0.50-0.66) vs 2.05 (0.86-2.36) µM, P < 0.0001]. Plasma MDA did not differ between the groups. The urinary nitrate-to-nitrite molar ratio (UNOXR), a measure of nitrite-dependent renal carbonic anhydrase (CA) activity, was higher in T1DM-T [1173 (738-1481), P < 0.0001] and T1DM-ND [1341 (1117-1615), P = 0.0007] compared to HC [540 (324-962)], but did not differ between T1DM-T and T1DM-ND (P = 0.272). The lower nitrite excretion in the children with T1DM may indicate enhanced renal CA-dependent nitrite reabsorption compared with healthy children. Yet, lower plasma nitrite concentration in the T1DM patients may have also contributed to the higher UNOXR. Patients' age correlated positively with plasma hArg and hArg/ADMA and urinary DMA/ADMA. Plasma ADMA and urinary ADMA, DMA, nitrite and nitrate correlated negatively with age of the T1DM-T children. Significant correlations were found between plasma hArg and plasma Arg (r = 0.468, P < 0.0001), and urinary DMA (r = -0.426, P = 0.0001), ADMA (r = -0.266, P = 0.021) and nitrate (r = -0.234, P = 0.043). Plasma hArg correlated positively with age at diagnosis (r = +0.337, P = 0.002). ADMA, but not hArg, correlated with HbA1c in T1DM-T (r = -0.418, P < 0.0001) and T1DM-ND (r = +0.879, P = 0.0016). The greatest differences between T1DM-T and T1DM-ND were observed for urinary ADMA, DMA/ADMA ratio, nitrite and nitrate. The Arg/NO pathway is altered in T1DM in childhood and adolescence, yet the role and the importance of hArg and ADMA in T1DM remain to be elucidated. In young T1DM patients, oxidative stress (lipid peroxidation) is not elevated.

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“…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%

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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Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS)

Abstract: Our study suggests that ADMA synthesis is elevated in sporadic FSGS. This finding argues for the involvement of ADMA in the pathogenesis of this disease in childhood.

Cited by 24 publications

References 27 publications

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

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

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