Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease

Xiao, Shen; Wagner, László; Schmidt, Rebecca J.; Baylis, Chris

doi:10.1046/j.1523-1755.2001.0590041466.x

Cited by 58 publications

(38 citation statements)

References 29 publications

(32 reference statements)

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“…In a small series (n = 11) we found that plasma ADMA levels are variable in CKD patients and are not correlated with severity of CKD. 94 Similar findings have been reported by Saran and colleagues. 90 By contrast, Fleck et al reported mild but consistent elevation of plasma ADMA levels (30-40% higher than normal) in CKD patients, which did not correlate with concentrations of plasma creatinine.…”

Section: Adma In Chronic Kidney Diseasesupporting

confidence: 85%

“…In a small group of patients (n = 11) with various primary diseases and approximately 30% residual renal function, an inhibitor of endothelial NOS was detected in the plasma of only 5 patients. 94 As shown in Figure 5, plasma ADMA levels in the CKD patients were predictive of endothelial NOS activity. ADMA concentrations were not correlated with primary disease or medication.…”

Section: Adma In End-stage Renal Diseasementioning

confidence: 88%

“…ADMA concentrations were not correlated with primary disease or medication. 94 There was no relationship between plasma creatinine or blood urea nitrogen and ADMA ( Figure 5), indicating that reduced catabolism of ADMA rather than impaired renal clearance was responsible for elevated plasma levels in the affected subgroup of CKD patients. This hypothesis was reinforced by the finding that plasma levels of SDMA (which is not a substrate for DDAH) were uniformly elevated, as was plasma creatinine ( Figure 5).…”

Section: Adma In End-stage Renal Diseasementioning

confidence: 96%

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Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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SummaryNitric oxide (NO) production is reduced in renal disease, partially due to decreased endothelial NO production. Evidence indicates that NO deficiency contributes to cardiovascular events and progression of kidney damage. Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of circulating endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine [ADMA]). Decreased L-arginine availability in chronic kidney disease (CKD) is due to perturbed renal biosynthesis of this amino acid. In addition, inhibition of transport of L-arginine into endothelial cells and shunting of L-arginine into other metabolic pathways (e.g. those involving arginase) might also decrease availability. Elevated plasma and tissue levels of ADMA in CKD are functions of both reduced renal excretion and reduced catabolism by dimethylarginine dimethylaminohydrolase (DDAH). The latter might be associated with loss-offunction polymorphisms of a DDAH gene, functional inhibition of the enzyme by oxidative stress in CKD and end-stage renal disease, or both. These findings provide the rationale for novel therapies, including supplementation of dietary L-arginine or its precursor L-citrulline, inhibition of non-NOproducing pathways of L-arginine utilization, or both. Because an increase in ADMA has emerged as a major independent risk factor in end-stage renal disease (and probably also in CKD), lowering ADMA concentration is a major therapeutic goal; interventions that enhance the activity of the ADMA-hydrolyzing enzyme DDAH are under investigation.

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Section: Adma In Chronic Kidney Diseasesupporting

confidence: 85%

Section: Adma In End-stage Renal Diseasementioning

confidence: 88%

Section: Adma In End-stage Renal Diseasementioning

confidence: 96%

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Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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“…Indeed, in several subsequent studies, significantly increased plasma ADMA levels have been documented in patients with terminal renal failure (27)(28)(29). It has also been shown that these ADMA concentrations are sufficiently high to reduce significantly NO production ex vivo (30). The results of Zoccali et al (29) in a prospective study that comprised 225 patients with terminal renal failure are also in line with an important pathophysiologic role of ADMA in (cardio)vascular dysfunction.…”

Section: Discussionmentioning

confidence: 84%

Asymmetric Dimethylarginine and Progression of Chronic Kidney Disease

Fliser

Kronenberg

Kielstein

et al. 2005

Journal of the American Society of Nephrology

301

214

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Reduced bioavailability of nitric oxide (NO) is thought to play an important role in progression of renal damage. The hypothesis that the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is involved in progression of kidney disease was tested. Plasma ADMA concentrations and other putative progression factors were assessed in 227 relatively young patients (45.7 ؎ 12.6 yr) with nondiabetic kidney diseases and mild to moderate renal failure. Progression assessed as doubling of serum creatinine and/or renal replacement therapy was evaluated prospectively. Baseline plasma ADMA concentrations in renal patients correlated significantly with serum creatinine (r ‫؍‬ 0.595), GFR (r ‫؍‬ ؊0.591), age (r ‫؍‬ 0.281), and proteinuria (r ‫؍‬ 0.184; all P < 0.01). Patients who reached an end point during follow-up were significantly older (P < 0.05) and had significantly higher creatinine, ADMA, and parathyroid hormone blood concentrations and protein excretion rates at baseline, whereas GFR and hemoglobin were significantly lower (all P < 0.01). Cox regression analysis revealed baseline serum creatinine (odds ratio 2.00; 95% confidence interval [CI] 1.61 to 2.49; P < 0.001) and ADMA (odds ratio 1.47; 95% CI 1.12 to 1.93 for an increment of 0.1 mol/L; P < 0.006) as independent predictors of disease progression. In patients with ADMA levels above median, progression was significantly faster (P < 0.0001), and their mean follow-up time to a progression end point was 52.8 mo (95% CI 46.9 to 58.8) as compared with 71.6 mo (95% CI 66.2 to 76.9) in patients with ADMA levels below the median. The endogenous NO synthase inhibitor ADMA is significantly associated with progression of nondiabetic kidney diseases. Lowering plasma ADMA concentrations may be a novel therapeutic target to prevent progressive renal impairment.

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“…methylated L -arginine derivatives and guanidino compounds), which can potentially depress NO synthase activity. Such compounds are thought to increase in the plasma more or less in proportion to the increase in the serum creatinine [22,23]. Furthermore, renal impairment is associated with oxidative stress which promotes NO inactivation by the production of reactive oxygen species, which avidly react with NO, producing cytotoxic reactive nitrogen species capable of nitrating proteins and damaging other molecules [24].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of vasculogenic erectile dysfunction after kidney transplantation

Abdel‐Hamid

2004

BJU International

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Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease

Cited by 58 publications

References 29 publications

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

Asymmetric Dimethylarginine and Progression of Chronic Kidney Disease

Mechanisms of vasculogenic erectile dysfunction after kidney transplantation

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