The protective effect of L-arginine on renal function

L-Arginine is a basic amino acid that serves as a precursor for nitric oxide (NO) synthesis in the body. By regulating vasomotor function, improving renal hemodynamics, inhibiting inflammatory responses and oxidative stress, it exerts potential renoprotective effects on renal function in patients with chronic kidney disease (CKD). However, its application is characterized by dose dependence and individual variability, requiring comprehensive evaluation based on patients’ renal function stages and metabolic status to avoid blind supplementation.

I. Core Mechanisms of L-Arginine in Renoprotection

1. Promoting Nitric Oxide Synthesis to Improve Renal Hemodynamics

Normal renal filtration and excretion functions rely on adequate and stable renal blood flow, and NO is a key factor regulating renal vasomotion.

Mechanism Pathway: L-Arginine is catalyzed by nitric oxide synthase (NOS) to produce NO. NO can dilate both the afferent and efferent renal arterioles, with a stronger vasodilatory effect on the efferent arterioles. This reduces intraglomerular pressure, decreases the ultrafiltration load on glomerular capillaries, and delays the progression of glomerulosclerosis.

Compensatory Effect in Pathological States: Patients with chronic kidney disease often exhibit decreased NOS activity and insufficient endogenous L-Arginine, leading to renal vasoconstriction and reduced renal blood flow. Supplementation with exogenous L-Arginine can restore NO synthesis by ensuring substrate sufficiency, ameliorate renal ischemia and hypoxia, and protect the integrity of the glomerular filtration barrier.

2. Inhibiting Inflammatory Responses and Oxidative Stress to Alleviate Renal Tissue Damage

The progression of chronic kidney disease is closely associated with persistent inflammatory responses and oxidative stress in renal tissues, which jointly damage renal tubular epithelial cells and glomerular mesangial cells.

Anti-inflammatory Effect: NO derived from L-Arginine can inhibit the activation of nuclear factor κB (NF-κB), reduce the release of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and alleviate inflammatory infiltration and fibrosis in renal tissues. Meanwhile, NO can regulate the activation status of immune cells, avoiding secondary renal damage caused by excessive immune responses.

Antioxidative Stress Effect: NO can scavenge excess reactive oxygen species (ROS) in the body, mitigating oxidative damage to renal cell membrane lipids, proteins, and DNA. In addition, L-Arginine can increase the activity of antioxidant enzymes (e.g., superoxide dismutase, glutathione peroxidase) in renal tissues by improving renal blood flow, enhancing the kidneys’ antioxidant capacity.

3. Regulating Glomerular Mesangial Cell Proliferation and Extracellular Matrix Deposition

Excessive proliferation of glomerular mesangial cells and abnormal deposition of extracellular matrix (ECM) are core pathological changes of glomerulosclerosis and key links in the progression of chronic kidney disease.

NO synthesized from L-Arginine can inhibit mesangial cell proliferation by suppressing the mitotic signaling pathways of mesangial cells. At the same time, NO can downregulate the expression of transforming growth factor-β (TGF-β), inhibit ECM synthesis and deposition, and delay the process of glomerular fibrosis.

For common chronic kidney disease types such as diabetic nephropathy, L-Arginine can further reduce hyperglycemia-induced glomerular damage and decrease urinary protein excretion by improving insulin sensitivity.

II. Precautions for L-Arginine Application in Patients with Chronic Kidney Disease

1. Dose Dependence and Safety Threshold

Recommended Dosage: Clinical studies on patients with chronic kidney disease have shown that the safe oral dosage of L-Arginine is usually 3–6 g/day, administered in 2–3 divided doses to avoid a single large-dose intake. A low dosage fails to effectively increase NO levels, while an excessive dosage may trigger adverse reactions.

Potential Risks: Excessive L-Arginine supplementation may lead to elevated blood ammonia levels. Particularly in patients with severely impaired renal function (CKD stages 4–5), the kidneys’ ability to excrete ammonia is compromised, and blood ammonia accumulation may induce hepatic encephalopathy-like symptoms (e.g., confusion, drowsiness). In addition, excessive NO may inhibit platelet aggregation, increasing the risk of bleeding.

2. Individualized Application Based on Renal Function Stages

CKD Stages 1–2 (Renal Compensation Stage): Patients have mild renal function impairment, with partial decline in endogenous L-Arginine synthesis capacity. Appropriate supplementation (3 g/day) can effectively improve renal blood flow, delay renal function deterioration, and achieve high safety.

CKD Stage 3 (Renal Decompensation Stage): L-Arginine should be used under monitoring of blood ammonia and renal function indicators. It is recommended to start with a low dosage (1.5 g/day) and gradually adjust according to the patient’s tolerance to avoid increasing the metabolic burden on the kidneys.

CKD Stages 4–5 (Renal Failure Stage/Uremic Stage): Patients have severely impaired renal excretion function, and routine supplementation with exogenous L-Arginine is not recommended unless there are clear clinical indications (e.g., severe renal ischemia). If necessary, it should be used with the support of hemodialysis or peritoneal dialysis, while closely monitoring blood ammonia and electrolyte levels.

3. Contraindicated and Cautious Populations

Contraindicated Populations: L-Arginine is contraindicated in patients with severe hepatic insufficiency (impaired hepatic ammonia metabolism leading to high risk of hyperammonemia), hyperkalemia (L-Arginine may affect renal potassium excretion), and those with hypersensitivity to L-Arginine.

Cautious Populations: Blood glucose should be monitored in patients with diabetic nephropathy, as L-Arginine may enhance insulin sensitivity and increase the risk of hypoglycemia. Patients with complicated cardiovascular diseases (e.g., heart failure) need to be evaluated for vasodilatory effects to avoid discomfort caused by blood pressure fluctuations.

III. Clinical Evidence and Limitations

1. Supportive Clinical Evidence

Multiple clinical studies have shown that for patients with early-stage chronic kidney disease (especially those with hypertensive renal damage and early diabetic nephropathy), oral administration of L-Arginine (3–6 g/day) for 3–6 consecutive months can significantly reduce urinary microalbumin excretion rate, increase estimated glomerular filtration rate (eGFR), and improve renal blood perfusion indicators. In addition, the combination of L-Arginine with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) can produce a synergistic renoprotective effect, delaying the progression of renal function impairment.

2. Research Limitations

Existing studies mainly focus on patients with early-stage chronic kidney disease, with few large-sample, long-term follow-up studies on patients with advanced renal failure. The efficacy and safety of L-Arginine in advanced kidney disease remain unclear.

The therapeutic effect of L-Arginine is greatly affected by individual differences among patients. Factors such as NOS gene polymorphism, comorbidity types, and medication compliance may lead to inconsistent efficacy.

There is a lack of unified clinical application guidelines, and different studies adopt varying dosages and courses of treatment, making it difficult to form standardized treatment regimens.

L-Arginine exerts certain renoprotective effects on renal function in patients with early-stage chronic kidney disease through mechanisms such as promoting NO synthesis, improving renal hemodynamics, inhibiting inflammation and oxidative stress. It can delay the progression of glomerulosclerosis and reduce urinary protein levels. However, its application must strictly follow the principles of individualization and dose control, with benefits and risks evaluated based on renal function stages. Caution is required when using L-Arginine in patients with advanced kidney disease. Future research needs to conduct more large-sample, long-term follow-up clinical studies to clarify the role of L-Arginine in the treatment of chronic kidney disease, providing more reliable evidence for clinical application.