Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure

Nicola, Luca De; Bellizzi, Vincenzo; Minutolo, Roberto; Andreucci, Michele; Capuano, Alfredo; Garibotto, Giacomo; Corso, Gaetano; Andreucci, Vittorio E.; Cianciaruso, Bruno

doi:10.1046/j.1523-1755.1999.00582.x

Cited by 38 publications

(23 citation statements)

References 33 publications

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“…In peripheral arterial disease patients, plasma L-arg concentration increased to a value of about 4.0 mM after 30-g dose infusion (32)(33)(34). Similar doses (about 15g) also have been administered to patients with chronic renal failure in a randomized controlled study (35). The administration of L-arg in sepsis is still debated.…”

Section: Resultsmentioning

confidence: 99%

Detrimental effects of Bartonella henselae are counteracted by l -arginine and nitric oxide in human endothelial progenitor cells

Salvatore

Casamassimi²,

Sommese³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Section: Resultsmentioning

confidence: 99%

Detrimental effects of Bartonella henselae are counteracted by l -arginine and nitric oxide in human endothelial progenitor cells

Salvatore

Casamassimi²,

Sommese³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Although important, these findings do not provide insight into the role of L-arginine in vascular function once CKD has already been established. Unfortunately, clinical studies in patients with CKD have not been as successful (7,12,16,18). In the present study, we initiated L-arginine treatment 4 wk after surgery to ensure that renal and vascular impairments had already developed.…”

Section: Discussionmentioning

confidence: 99%

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

Martens

Kuczmarski

Kim

et al. 2014

American Journal of Physiology-Renal Physiology

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. Voluntary wheel running augments aortic L-arginine transport and endothelial function in rats with chronic kidney disease. Am J Physiol Renal Physiol 307: F418 -F426, 2014. First published June 25, 2014 doi:10.1152/ajprenal.00014.2014.-Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor L-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endotheliumdependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent 5 ⁄6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUNϩARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10 Ϫ9 -10 Ϫ5 M) as indicated by a reduced area under the curve (AUC; 44.56 Ϯ 9.01 vs 100 Ϯ 4.58, P Ͻ 0.05) and reduced maximal response (Emax; 59.9 Ϯ 9.67 vs. 94.31 Ϯ 1.27%, P Ͻ 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUNϩARG-treated animals. Maximal relaxation was elevated above SED in RUNϩARG animals only. L-[ 3 H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUNϩARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with L-arginine. endothelial dysfunction; chronic kidney disease; L-arginine; exercise ENDOTHELIAL DYSFUNCTION CONTRIBUTES to the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) and is primarily associated with a decrease in nitric oxide (NO) production and impaired endothelium-dependent relaxation (EDR) (32). The decline in endothelial function precedes the development of atherosclerosis (17, 48) and has been extensively studied as a potential therapeutic target to treat CVD; however, the specific mechanisms of endothelial dysfunction in CKD have not been fully elucidated. Patients with CKD are more likely to die of CVD than progress to end-stage renal disease (26, 42); therefore, novel treatments to improve endothelial function in CKD are needed to reduce CVD-related mortality in CKD.Insufficient availability of the NO precursor L-arginine likely contributes to reduced NO synthesis in CKD (6). Interestingly, the use of L-arginine in studies of endothelial dysfunction in late-stage CKD has produced mixed results (7, 16) unlike other conditions where it has been largely effective (8,13,15,24). Evidence from cell culture studies suggests that urea and other uremic toxins inhibit L-arginine uptake into endothelial cells (52, 54) by...

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“…75,76 However, these positive results have failed to translate into benefit in clinical trials. 77,78 The lack of efficacy found in such studies has been attributed to intrinsic impairment in the NO synthesis apparatus. For example, commonly found features of CKD, such as elevation of ADMA levels or a deficiency in cofactors for eNOS (such as tetrahydrobiopterin), may negate the benefit of l-arginine supplementation and lead to enhanced free radical generation.…”

Section: Other Therapeutic Approaches To Enhance No Signaling L-arginmentioning

confidence: 99%

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

Brown

Dhaun²,

Goddard³

et al. 2014

Hypertension

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Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure

Abstract: In moderate CRF, the tonic release of NO is constant and, likely, not impaired, and ARG supplementation does not lead to an enhancement of NO activity, thus resulting in no renal effect.

Cited by 38 publications

References 33 publications

Detrimental effects of Bartonella henselae are counteracted by l -arginine and nitric oxide in human endothelial progenitor cells

Detrimental effects of Bartonella henselae are counteracted by l -arginine and nitric oxide in human endothelial progenitor cells

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

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