A 2017 review discusses pain management for patients with chronic kidney disease (CKD). For patients with moderate pain (score of 4 to 6) and CKD, tramadol may be considered because it is not known to be directly nephrotoxic. In patients with advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2), tramadol and its metabolite can accumulate causing increased blood levels, which can lead to respiratory depression and reduced seizure threshold. The authors do not report whether there is a potential for tramadol accumulation to precipitate renal failure in patients with CKD. [1]
A 2018 review stated that tramadol is often a safer option over NSAIDs for pain management in CKD patients. However, due to its dual mechanism of action as a central opioid agonist and central nervous system (CNS) reuptake inhibitor of serotonin and norepinephrine, the O-demethylation product of tramadol metabolism has a greater affinity for opioid mu-receptor than the original compound. Variability in the conversion can be introduced depending on the patients receiving tramadol, who can be slow, fast, or ultra-fast metabolizers of the drug. The authors suggested that the resulting potential adverse effects (seizures, hypoglycemia, serotonin syndrome, and opioid dependence) may be unpredictable. [2]
Additionally, a 2019 review specifically discussed opioid management, including the use of tramadol, in older adults with CKD. Tramadol and its active metabolites are predominantly renally cleared. As recommended by tramadol’s product labels, renal dose adjustment is required with immediate-release formulation in individuals with creatinine clearance (CrCl) <30 mL/min; whereas the use of extended-release formulation should be avoided in this population. Concerning the increased risk of seizures and central nervous system adverse effects in older adults with CKD with prolonged tramadol exposure, researchers recommend against either formulation in the elderly with CKD. [3]
A 2020 prospective cohort study conducted a comparative analysis of harm from opioids versus NSAIDs in CKD, using 30-day analgesic use reported at annual visits of 3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) study. Over a median follow-up of 6.84 years, 391 (9.9%) and 612 (15.5%) participants reported baseline opioid and NSAID use, respectively. A sub-cohort analysis was also conducted, including patients who ever consumed another (non-opioid, non-NSAID) analgesic or tramadol at baseline or during follow-up as a surrogate for the need of pain relief. Specifically, 18/391 (4.6%) opioid users and 17/612 (2.8%) NSAID users received tramadol at baseline as well. Pooled results demonstrated time-updated opioid use to be associated with the kidney disease composite outcome, kidney failure with kidney replacement therapy (KRT), death (hazard ratio of 1.4 [95% confidence interval (CI) 1.2 to 1.7], 1.4 [95% CI 1.1 to 1.7], and 1.5 [95% CI 1.2 to 2.0], respectively), and hospitalization (rate ratio 1.7; 95% CI 1.6 to 1.9) versus opioid non-users. Sub-cohort analysis of participants with exposure to other analgesics or tramadol showed similar results. While time-upated NSAID use was also found to be associated with an increased risk for the kidney disease composite and hospitalization, results were not significant in the sub-cohort. Findings from this observational study are limited to recall bias on analgesic use and unadjusted confounding factors, such as indication. Additionally, use of tramadol is not evaluated as an individual analgesic in terms of its long-term effects on renal outcomes in CKD patients. [4]