What is the effect of Low-Dose Naltrexone (LDN) on kidney function?

From the Guidelines

Low-dose naltrexone (LDN) is not recommended for patients with moderate to severe renal impairment, and should be avoided in end-stage renal disease, due to the potential risk of reduced efficacy or increased toxicity 1. When considering the use of LDN in patients with kidney disease, it is essential to weigh the potential benefits against the potential risks. While LDN may have anti-inflammatory and immune-modulating properties that could potentially benefit kidney health, the current evidence is limited, and the potential risks associated with its use in patients with renal impairment cannot be ignored. Some key points to consider when evaluating the use of LDN in patients with kidney disease include:

• The recommended dose of naltrexone-bupropion ER should be reduced by one-half in patients with moderate to severe renal impairment, and avoided in end-stage renal disease 1.
• The use of LDN may be associated with potential side effects, such as sleep disturbances, vivid dreams, headaches, or gastrointestinal upset, particularly during the first week of treatment.
• Patients with kidney disease should consult with their nephrologist before starting LDN, as individual responses may vary, and it should be used as part of a comprehensive treatment approach. In terms of the potential benefits of LDN on kidney health, some studies suggest that it may have anti-inflammatory and immune-modulating properties that could potentially benefit patients with conditions like diabetic nephropathy, chronic kidney disease, or autoimmune kidney disorders. However, these findings are based on limited evidence, and more research is needed to fully understand the effects of LDN on kidney health. Overall, while LDN may have potential benefits for kidney health, the current evidence is limited, and the potential risks associated with its use in patients with renal impairment cannot be ignored. Therefore, LDN is not recommended for patients with moderate to severe renal impairment, and should be avoided in end-stage renal disease, due to the potential risk of reduced efficacy or increased toxicity 1.

From the FDA Drug Label

Naltrexone hydrochloride and its primary metabolite are excreted primarily in the urine, and caution is recommended in administering the drug to patients with renal impairment Both parent drug and metabolites are excreted primarily by the kidney (53% to 79% of the dose) The renal clearance for naltrexone ranges from 30 to 127 mL/min and suggests that renal elimination is primarily by glomerular filtration.

• Key Points:
  • Naltrexone is excreted primarily in the urine
  • Caution is recommended when administering naltrexone to patients with renal impairment
  • Renal elimination is primarily by glomerular filtration
• Clinical Decision: Naltrexone should be used with caution in patients with renal impairment, as it is primarily excreted by the kidneys and may accumulate to toxic levels in patients with decreased renal function 2, 2.

From the Research

LDN and Kidney Effects

• The effect of LDN (Low-Dose Naltrexone) on kidneys is not directly addressed in the provided studies, but the pharmacokinetics of naltrexone in patients with end-stage renal disease can provide some insights 3, 4.
• A study on naltrexone pharmacokinetics in patients undergoing hemodialysis found that hemodialysis has little effect on naltrexone blood levels, and consequently, on drug pharmacokinetics 3.
• Another study on the effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene, an opioid antagonist, found that hemodialysis does not result in clinically significant alterations in the disposition of nalmefene or its primary metabolite 4.
• The renal clearance data from a study on naltrexone disposition, metabolism, and effects indicate that naltrexone is partially reabsorbed while its metabolite, beta-naltrexol, is actively secreted by the kidney 5.
• There is no direct evidence on the effect of LDN on kidney function, but the provided studies suggest that naltrexone and its metabolites are affected by renal function, and dosage adjustments may be necessary in patients with advanced renal disease 3, 6, 4, 5.

Naltrexone and Renal Disease

• Naltrexone can be used to manage pruritus in patients with end-stage renal disease, and its pharmacokinetics are not significantly altered by hemodialysis 3, 6.
• The study on end-stage renal disease symptom management suggests that naltrexone can be helpful for pruritus, but the patient's renal function must be considered when selecting a drug and determining the dosage 6.
• The pharmacokinetics of naltrexone in patients with end-stage renal disease are affected by the decreased hepatic first-pass metabolism and renal impairment, leading to increased levels of the drug in plasma 3.

LDN and Cancer

• A study on low-dose naltrexone suggests that it may have potential benefits for patients with cancer, including reducing tumor growth and modifying the immune system 7.
• However, this study does not address the effect of LDN on kidney function or its pharmacokinetics in patients with renal disease.