L-Arginine for Kidney Disease
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byPaul J Fadel, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: The University of Texas at Arlington
Must not be taking: Menopausal drugs
Disqualifiers: Myocardial infarction, Heart failure, Cancer, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and death. An overactive sympathetic nervous system in CKD patients is one of the major mechanisms increasing the cardiovascular risks in this patient population. A potential signal driving sympathetic nerve activity (SNA) involves accumulation of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). ADMA is elevated in CKD and is a strong, independent predictor of future cardiovascular events in these patients. .
The goal of this study is to determine whether overcoming the accumulation of endogenous ADMA with acute L-arginine infusion reduces SNA in CKD patients.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are taking menopausal drugs or treatment for diabetic neuropathy, you may not be eligible to participate.
What evidence supports the effectiveness of the drug L-Arginine for kidney disease?
Some studies suggest that L-Arginine might help improve kidney function in certain conditions by increasing blood flow and reducing inflammation, but its effects can vary depending on the specific type of kidney disease. In animal studies, L-Arginine has shown benefits in conditions like hypertension and diabetes-related kidney issues, but its effectiveness in humans is not fully understood and may not be beneficial in all cases.
12345Is L-Arginine safe for humans with kidney disease?
L-Arginine has shown both beneficial and harmful effects in animal studies, depending on the specific kidney condition. In humans, it does not change the course of chronic glomerular diseases, but it may be beneficial in some other kidney conditions. More research is needed to fully understand its safety and effects.
14678How does the drug L-Arginine differ from other treatments for kidney disease?
L-Arginine is unique because it is a semi-essential amino acid that helps produce nitric oxide, which can improve blood flow and kidney function. Unlike other treatments, it may have both beneficial and harmful effects depending on the specific kidney condition, and its role in treating kidney disease is not fully understood.
34589Eligibility Criteria
This trial is for adults aged 35-75 with moderate to severe chronic kidney disease (stages 3 and 4), who have a specific level of kidney function. It's not open to those with heart failure, severe anemia, HIV, pregnant or breastfeeding women, very low blood pressure or high resting heart rate, current smokers, cancer patients undergoing treatment, or those on certain medications.Inclusion Criteria
I am between 35 and 75 years old.
My kidney function is moderately to severely reduced.
Exclusion Criteria
anemia (hemoglobin <8 g/dl)
I am receiving treatment for nerve pain due to diabetes.
I have heart failure.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive intravenous infusion of L-arginine or saline for 30 minutes
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
1-2 weeks
Participant Groups
The study tests if L-arginine infusion can reduce overactivity in the nervous system among CKD patients by counteracting ADMA accumulation. Participants will either receive this amino acid or a placebo in order to compare outcomes.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: L-arginineExperimental Treatment1 Intervention
Intravenous infusion of L-arginine (250-350 mg/kg) will be performed for 30 minutes.
Group II: SalinePlacebo Group1 Intervention
Saline will be infused for 30 minutes
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UT SouthwesternDallas, TX
University of DelawareNewark, DE
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Who Is Running the Clinical Trial?
The University of Texas at ArlingtonLead Sponsor
References
From rats to man: a perspective on dietary L-arginine supplementation in human renal disease. [2019]Experimental studies have shown both therapeutic and detrimental consequences of modifying dietary L-arginine intake in renal diseases which likely reflect the complexity of L-arginine metabolism. L-Arginine intake is semi-essential and provides substrate for a number of L-arginine metabolites involved in renal pathology. Dietary L-arginine restriction has been identified as a key mediator of the beneficial effects of low protein diets on human renal fibrosis. Supplementing dietary L-arginine in renal diseases with increased iNOS expression appears to be detrimental and thus, may be harmful in immune-mediated human kidney disorders. Increasing L-arginine intake is beneficial in experimental models of hypertensive renal disease. Based upon available data, we believe additional questions must be answered experimentally, not only to prevent an adverse outcome in humans, but to enhance our chances of human trials which will result in substantially better amelioration of disease than currently available.
Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. [2013]Supplementation with L-arginine (ARG) strikingly ameliorates proteinuria and glomerulosclerosis in remnant rats by overcoming nitric oxide (NO) deficiency. Whether or not the same holds true in humans is unknown. This study aimed at evaluating the effects of ARG on the NO system and renal function in proteinuric patients with moderate chronic renal failure (CRF).
L-arginine supplementation in young renal allograft recipients with chronic transplant dysfunction. [2013]L-arginine (LA), the precursor of nitric oxide (NO), was suggested to be beneficial in many forms of renal disease: hypertension, ureteral obstructive nephropathy and cyclosporin A (CsA) nephrotoxicity.
Role of L-arginine in the pathogenesis and treatment of renal disease. [2023]L-arginine is a semi essential amino acid and also a substrate for the synthesis of nitric oxide (NO), polyamines, and agmatine. These L-arginine metabolites may participate in the pathogenesis of renal disease and constitute the rationale for manipulating L-arginine metabolism as a strategy to ameliorate kidney disease. Modification of dietary L-arginine intake in experimental models of kidney diseases has been shown to have both beneficial as well as deleterious effects depending on the specific model studied. L-arginine supplementation in animal models of glomerulonephritis has been shown to be detrimental, probably by increasing the production of NO from increased local expression of inducible NO synthase (iNOS). L-arginine supplementation does not modify the course of renal disease in humans with chronic glomerular diseases. However, beneficial effects of L-arginine supplementation have been reported in several models of chronic kidney disease including renal ablation, ureteral obstruction, nephropathy secondary to diabetes, and salt-sensitive hypertension. L-arginine is reduced in preeclampsia and recent experimental studies indicate that L-arginine supplementation may be beneficial in attenuating the symptoms of preeclampsia. Administration of exogenous L-arginine has been shown to be protective in ischemic acute renal failure. In summary, the role of L-arginine in the pathogenesis and treatment of renal disease is not completely understood and remains to be established.
Can L-arginine manipulation reduce renal disease? [2013]The administration of L-arginine to normal animals leads to an increase in renal plasma flow and glomerular filtration rate (GFR). Administration on a chronic basis of N-nitro-L-arginine methylester (L-NAME), an antagonist of L-arginine, increases blood pressure and reduces the ultrafiltration coefficient. In rats with ureteral obstruction, the administration of L-arginine increases GFR and renal blood flow in the postobstructive kidney. Administration of L-arginine decreased the macrophage infiltration of the renal parenchyma that occurs in this model. L-arginine administration also blunted the increases in interstitial volume, collagen deposition, and expression of alpha-smooth muscle actin in the obstructed kidney. L-arginine administration to rats with subtotal nephrectomy reduced proteinuria and the number of abnormal glomeruli. Some of these effects may be mediated by nitric oxide (NO). In rats with diabetes, administration of L-arginine decreased hyperfiltration and proteinuria. The role of arginine and NO in glomerular diseases is controversial. In general most of the evidence indicates a beneficial change in the renal pathology and function in animals with glomerulonephritis receiving L-arginine. Most of the evidence indicates that the L-arginine-NO pathway has an important role in ameliorating hypertension, renal disease, inflammation and atherosclerosis.
Enhancement of nitric oxide synthesis by L-arginine supplementation in renal disease: is it good or bad? [2013]L-Arginine is a important component of our diet characterized by multiple physiological and pharmacological actions. In the last decade, this amino acid has attracted major interest since it has been identified as the natural substrate of nitric oxide, and is now recognized to play a major role in the regulation of vascular tone. This review, while summarizing the knowledge of the renal actions of the L-arginine/nitric oxide pathway in health and renal disease, focuses on the potential therapeutic implications of the increase in nitric oxide synthesis attained by L-arginine supplementation.
L-arginine: a new opportunity in the management of clinical derangements in dialysis patients. [2016]L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism. Rats receiving arginine-supplemented parenteral nutrition showed an increased ability to synthesize acute phase proteins when challenged with sepsis. Finally, L-arginine exerts antihypertensive and antiproliferative effects on vascular smooth muscles. It has been shown to reduce systemic blood pressure in some forms of experimental hypertension. Endothelial dysfunction and reduced nitric oxide bioactivity are associated with increased incidence of cardiovascular diseases. A beneficial effect of acute and chronic L-arginine supplementation on endothelial derived nitric oxide production and endothelial function has been shown. In end-stage renal disease patients, the rate of de novo arginine synthesis seemed to be preserved. Our preliminary data on a group of dialysis patients showed that predialysis arginine levels were stable in a normal range during the dialysis session and that hypertensive patients had lower arginine-citrulline ratio than normotensive patients.
Role of arginine in health and in renal disease. [2017]In addition to participating in protein synthesis in cells and tissues, L-arginine is essential for the synthesis of urea, creatine, creatinine, nitric oxide, and agmatine and influences hormonal release and the synthesis of pyrimidine bases. This places L-arginine, its precursors and its metabolites at the center of the interaction of different metabolic pathways and interorgan communication. Thus L-arginine participates in changing the internal environment in different but simultaneous ways, ranging from disposal of protein metabolic waste, muscle metabolism, vascular regulation, immune system function, and neurotransmission, to RNA synthesis and hormone-mediated regulation of the internal milieu. In normal rats, inhibition of the nitric oxide pathway results in systemic hypertension and decreased glomerular filtration rate and effective renal plasma flow. If the inhibition of this pathway is sustained, then glomerulosclerosis and death from uremia follow. Dietary intervention with L-arginine has resulted in amelioration of a number of experimental kidney diseases, such as those caused by subtotal nephrectomy, diabetic, nephropathy, cyclosporin A administration, salt-sensitive hypertension, ureteral obstruction, puromycin amino-nucleoside nephrosis, kidney hypertrophy due to high-protein feeding, and glomerular thrombosis due to administration of lipopolysaccharide. The present review addresses the current evidence for the beneficial effects of dietary intervention with L-arginine in a number of experimental renal diseases and describes the basis for the concept of L-arginine deficiency (absolute or relative) in certain settings in which supplementation of the diet with this amino acid may be beneficial.
Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. [2019]We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham-operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS)