Can tramadol (ultram) cause kidney damage, specifically impaired renal function, in patients?

From the Guidelines

Tramadol can cause kidney damage or impaired renal function, particularly in patients with pre-existing kidney impairment, and its use should be avoided or carefully managed in such cases. Tramadol is primarily metabolized by the liver, with its metabolites being excreted through the kidneys. For patients with normal kidney function, tramadol is considered relatively safe from a renal perspective. However, in patients with pre-existing kidney impairment, dose adjustments may be necessary as the drug and its metabolites can accumulate, potentially worsening kidney function or causing adverse effects 1.

Key Considerations

• Tramadol should be avoided in patients with renal impairment, unless there are no alternatives, due to the risk of accumulation of the parent drug or active metabolites 1.
• For patients with severe renal impairment (creatinine clearance less than 30 mL/min), the recommended dosing is typically reduced to 50-100 mg every 12 hours, with a maximum daily dose of 200 mg.
• Patients taking tramadol should stay well-hydrated and report any symptoms such as decreased urination, swelling in extremities, or unusual fatigue that might indicate kidney problems.
• While direct nephrotoxicity is uncommon, tramadol can occasionally cause urinary retention or contribute to acute kidney injury in specific circumstances, such as when it leads to hypotension or when used in combination with other nephrotoxic medications.

Recommendations for Patients with Renal Impairment

• Clinicians may rotate to methadone, if not contraindicated, as this agent is excreted fecally 1.
• Opioids primarily eliminated in urine, such as fentanyl, oxycodone, and hydromorphone, should be carefully titrated and frequently monitored for risk or accumulation of the parent drug or active metabolites 1.
• More frequent clinical observation and opioid dose adjustment should be performed for patients with renal or hepatic impairment who receive opioids 1.

From the FDA Drug Label

Renal Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1 In patients with creatinine clearances of less than 30 mL/min, adjustment of the dosing regimen is recommended

Tramadol and Kidney Damage: Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. Impaired renal function can lead to a decreased rate and extent of excretion of tramadol and its active metabolite, M1. However, the FDA drug label does not directly state that tramadol causes kidney damage.

• Key Points:
  • Impaired renal function affects tramadol excretion
  • Dosing regimen adjustment is recommended for patients with creatinine clearances of less than 30 mL/min
  • Tramadol is not directly stated to cause kidney damage in the FDA drug label 2 2

From the Research

Tramadol and Kidney Damage

• Tramadol, also known as Ultram, is a medication used to treat moderate to severe pain, but its use has been associated with kidney damage in some cases 3, 4, 5, 6.
• Studies have shown that high doses or chronic administration of tramadol can cause renal impairment, including increased serum creatinine and blood urea nitrogen (BUN) levels, as well as histopathological changes in the kidney such as inflammation, necrosis, and tubular degeneration 3, 5, 6.
• The mechanism of tramadol-induced renal injury is thought to involve mitochondrial dysfunction and oxidative stress, leading to the formation of reactive oxygen species (ROS) and lipid peroxidation 5.
• Exercise, such as high-intensity interval training (HIIT), may have a protective effect against tramadol-induced nephrotoxicity, as it has been shown to reduce oxidative stress and improve antioxidant capacity in the kidney 4.
• It is essential to monitor kidney function and adjust tramadol dosing accordingly, especially in patients with pre-existing kidney disease, to minimize the risk of kidney damage 7.

Risk Factors for Tramadol-Induced Kidney Damage

• High doses or chronic administration of tramadol
• Pre-existing kidney disease
• Combination with other medications that can affect kidney function
• Lack of proper dosing and monitoring of kidney function

Clinical Implications

• Healthcare providers should be aware of the potential risk of kidney damage associated with tramadol use and monitor patients accordingly 3, 7.
• Patients with kidney disease or those taking medications that can affect kidney function should be cautious when using tramadol and have their kidney function monitored regularly.
• Further research is needed to fully understand the mechanisms of tramadol-induced kidney damage and to develop strategies for preventing and treating this condition.