L-Arginine for Kidney Disease

Recruiting at 1 trial location

Overseen By Paul J Fadel, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas at Arlington

Must not be taking: Menopausal drugs

Disqualifiers: Myocardial infarction, Heart failure, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if L-arginine, administered through an IV, can lower the risk of heart problems in individuals with chronic kidney disease (CKD). CKD often triggers an excessive stress response, potentially leading to heart issues. L-arginine may help by reducing certain harmful chemicals that accumulate in people with CKD. Suitable participants are those with CKD in stages 3 or 4, who frequently face related health issues, such as increased heart risk. As a Phase 4 trial, this research focuses on understanding how this FDA-approved treatment can benefit more 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 is the safety track record for L-Arginine?

Research has shown that L-arginine is usually safe at normal doses. The body naturally produces this substance. Some studies suggest it might help protect the kidneys. However, using it in very high amounts or for extended periods might harm kidney and blood vessel health. For short-term use, as in this study, side effects are unlikely. Consulting a healthcare professional before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for kidney disease, which often involve blood pressure medications, diuretics, or dialysis, L-Arginine is administered through an intravenous infusion, offering a novel approach. Researchers are excited about L-Arginine because it works by enhancing nitric oxide production, which can improve blood flow to the kidneys and potentially slow disease progression. This mechanism is different from typical treatments, which often focus on managing symptoms rather than directly targeting blood flow and kidney function. This fresh angle offers hope for more effective management of kidney disease.

What evidence suggests that L-Arginine might be an effective treatment for kidney disease?

Research has shown that L-arginine might help calm an overactive nervous system in people with chronic kidney disease (CKD). This is important because an overactive nervous system can increase the risk of heart problems in these patients. Studies have found that L-arginine can positively affect kidney function and related health indicators. Some evidence also suggests that L-arginine supplements may help manage kidney health and body weight. In this trial, participants will receive either L-arginine or a placebo. Overall, while the effects of L-arginine can vary, it shows promise for reducing certain risks in CKD patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Paul J Fadel, PhD

Principal Investigator

University of Texas at Arlington

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• L-Arginine
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: L-arginine Experimental Treatment 1 Intervention

Intravenous infusion of L-arginine (250-350 mg/kg) will be performed for 30 minutes.

Group II: Saline Placebo Group 1 Intervention

Saline will be infused for 30 minutes

Who Is Running the Clinical Trial?

The University of Texas at Arlington

Lead Sponsor

Trials

48

Recruited

7,300+

Published Research Related to This Trial

Chronic administration of L-arginine in animal models leads to increased renal plasma flow and glomerular filtration rate (GFR), suggesting it may improve kidney function and reduce hypertension.

L-arginine also appears to decrease inflammation and damage in the kidneys, as seen in models of ureteral obstruction and diabetes, potentially through mechanisms involving nitric oxide (NO).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can L-arginine manipulation reduce renal disease? Klahr, S.[2013]

L-Arginine is crucial for infants, children, and pregnant women, serving as a substrate for multiple enzymes and playing a key role in synthesizing important compounds like nitric oxide and creatine.

Supplementation with L-arginine may improve outcomes in sepsis by enhancing microcirculation and protein synthesis, and it has shown potential antihypertensive effects by improving endothelial function and nitric oxide production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-arginine: a new opportunity in the management of clinical derangements in dialysis patients. Bellinghieri, G., Santoro, D., Mallamace, A., et al.[2016]

L-arginine plays a complex role in kidney disease, with its supplementation showing both harmful effects in certain conditions like glomerulonephritis and beneficial effects in others, such as chronic kidney disease models.

While L-arginine does not appear to alter the progression of chronic glomerular diseases in humans, it may help alleviate symptoms of preeclampsia and protect against ischemic acute renal failure, indicating potential therapeutic uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of L-arginine in the pathogenesis and treatment of renal disease. Cherla, G., Jaimes, EA.[2023]

L-arginine supplementation in young renal allograft recipients treated with cyclosporin A did not significantly improve renal function or reduce proteinuria, indicating limited efficacy in this patient group.

However, L-arginine did increase urinary excretion of urea and nitrates, suggesting some metabolic effects, but the unchanged levels of cGMP indicate that the expected nitric oxide pathway may be inhibited in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-arginine supplementation in young renal allograft recipients with chronic transplant dysfunction. Zhang, XZ., Ardissino, G., Ghio, L., et al.[2013]

Modifying dietary L-arginine intake can have both positive and negative effects on kidney health, highlighting the complexity of its metabolism in renal diseases.

While restricting L-arginine can help reduce renal fibrosis in low protein diets, increasing L-arginine may be harmful in certain kidney disorders, particularly those with high iNOS expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From rats to man: a perspective on dietary L-arginine supplementation in human renal disease. Peters, H., Border, WA., Noble, NA.[2019]

L-Arginine is crucial for our diet and has significant physiological roles, particularly in regulating blood vessel function through its conversion to nitric oxide.

Supplementing with L-Arginine may enhance nitric oxide production, which could have therapeutic benefits for kidney health and diseases related to renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of nitric oxide synthesis by L-arginine supplementation in renal disease: is it good or bad? De Nicola, L., Minutolo, R., Bellizzi, V., et al.[2013]

In a study of proteinuric patients with moderate chronic renal failure (CRF), L-arginine supplementation did not improve renal function or reduce proteinuria after six months of treatment, indicating a lack of efficacy in this population.

Despite an increase in plasma arginine levels with supplementation, there was no significant enhancement in nitric oxide (NO) activity or improvement in renal functional reserve, suggesting that the NO system may not be impaired in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. De Nicola, L., Bellizzi, V., Minutolo, R., et al.[2013]

L-arginine plays a crucial role in various metabolic processes, including protein synthesis, nitric oxide production, and hormone regulation, which are essential for maintaining kidney health and function.

Dietary supplementation with L-arginine has shown promise in improving several experimental kidney diseases in rats, suggesting that it may help mitigate conditions like diabetic nephropathy and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of arginine in health and in renal disease. Reyes, AA., Karl, IE., Klahr, S.[2017]

Dietary supplementation with L-arginine for 6 weeks improved kidney function in female Sprague-Dawley rats with significant renal mass reduction, as indicated by higher glomerular filtration rates and better kidney structure compared to control rats without supplementation.

Rats with reduced kidney mass that received L-arginine showed improved urine urea excretion and maintained comparable blood pressure and plasma chemistries, suggesting that L-arginine may help mitigate some adverse effects of renal disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. Reyes, AA., Purkerson, ML., Karl, I., et al.[2019]

Citations

1. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.582155/full

Detrimental Effects of Chronic L-Arginine Rich Food on ... The results do not support benefits of long-term L-arginine supplementation. It rather accelerates functional decline of kidney and vasculature in aging.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1051227618301973

The Renal Safety of L-Carnitine, L-Arginine, and Glutamine ... Arginine appears to have both beneficial and detrimental effects on kidney function. However, adverse effects are unlikely to occur with the routine doses (from ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15465789/

Role of L-arginine in the pathogenesis and treatment ... Modification of dietary L-arginine intake in experimental models of kidney diseases has been shown to have both beneficial as well as deleterious effects.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03982160?term=AREA%5BBasicSearch%5D(l%20600)&rank=6

L-arginine to Reduce Sympathetic Nerve Activity in CKD ... Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and death. An overactive sympathetic nervous system in CKD patients is ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0985056224001444

The impact of L-arginine supplementation on kidney ... Findings from this study suggest that an L-Arginine supplement might be beneficial to modulating kidney biomarkers and body weight indices.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7851093/

Detrimental Effects of Chronic L-Arginine Rich Food on ... The results do not support benefits of long-term L-arginine supplementation. It rather accelerates functional decline of kidney and vasculature in aging.

7. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251455

Evaluating the Safety of Arginine-Only Renal Protection on ... These findings suggest that arginine monotherapy offers adequate nephroprotection, emphasizing its potential as an accessible alternative for ...