Does tramadol (tramadol hydrochloride) affect renal function?

From the Guidelines

Tramadol should be avoided in patients with renal insufficiency (GFR <30 mL/min/1.73 m2) and ESRD due to the risk of accumulation of the drug and its metabolites, which can lead to increased side effects or complications. Tramadol is primarily metabolized by the liver, with its metabolites being excreted through the kidneys 1. In patients with healthy kidneys, tramadol generally has minimal direct effects on kidney function. However, in patients with pre-existing kidney impairment, dosage adjustments may be necessary to prevent accumulation of the drug and its metabolites 1.

Key Considerations

• Tramadol can occasionally cause urinary retention in some patients, which might indirectly affect kidney function 1.
• It may also rarely cause interstitial nephritis, a type of kidney inflammation, as an allergic reaction 1.
• For patients with severe kidney disease, reducing the dosage and extending the time between doses is typically recommended 1.
• Clinicians should perform more frequent clinical observation and opioid dose adjustment in patients with renal or hepatic impairment who receive opioids, including tramadol 1.

Recommendations

• Patients with kidney disease should inform their healthcare provider before taking tramadol so they can determine the appropriate dosage for their condition 1.
• Alternative opioids, such as methadone, may be considered in patients with renal impairment, as they are excreted fecally and may be safer in this population 1.

From the FDA Drug Label

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 is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. Renal Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1 The total amount of tramadol and M1 removed during a 4-hour dialysis period is less than 7% of the administered dose Tramadol affects kidney function by decreasing the rate and extent of excretion of tramadol and its active metabolite, M1, in patients with impaired renal function.

• In patients with creatinine clearances of less than 30 mL/min, adjustment of the dosing regimen is recommended 2.
• Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys 2.
• Renal impaired function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1 2.
• Dosing reduction is recommended in patients with creatinine clearances of less than 30 mL/min 2.

From the Research

Tramadol and Kidney Function

• Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates, and its metabolites are mainly excreted via the kidneys 3.
• A study found that new tramadol and opioid prescription rates upon hospital discharge for CKD stage IV and V and ESRD patients decreased after the CDC GPOCP publication, and among the patients discharged with a new tramadol prescription, 94 (72.3%) patients were dosed correctly based on kidney function 4.
• A case report described a 16-year-old female who developed transient acute renal impairment after an intentional tramadol ingestion, which improved over 6 days with minimal intervention 5.
• An animal study found that tramadol-induced renal injury is involved in the mechanism of mitochondrial dysfunction and oxidative stress, and renal histopathological alterations included inflammation, necrosis, and tubular degeneration in the kidney of tramadol-treated animals 6.
• Although the above studies suggest a potential link between tramadol and kidney function, it is essential to note that another study on acetaminophen use and risk of renal impairment found that acetaminophen is associated with a significantly increased risk of newly developing renal impairment in adults, but this study is not directly related to tramadol 7.

Key Findings

• Tramadol metabolites are excreted via the kidneys, and its use may be associated with renal impairment in certain cases 3, 5, 6.
• Tramadol prescription rates have decreased after the CDC GPOCP publication, and correct dosing based on kidney function is crucial 4.
• The mechanism of tramadol-induced renal injury involves mitochondrial dysfunction and oxidative stress 6.