Buprenorphine Does Not Accumulate in Dialysis Patients
Buprenorphine is one of the safest opioids for dialysis patients because it does not accumulate—it undergoes primarily hepatic metabolism with fecal excretion, and neither the parent drug nor its metabolites require dose adjustment in renal failure. 1
Why Buprenorphine is Safe in Dialysis
Buprenorphine's unique pharmacokinetic profile makes it ideal for patients with end-stage renal disease:
No dose adjustment needed: Buprenorphine is mainly metabolized in the liver to norbuprenorphine (a metabolite 40 times less potent than the parent compound) and excreted predominantly in feces, not urine 1
Unchanged pharmacokinetics in renal failure: A study of dialysis-dependent patients receiving IV buprenorphine 0.3 mg showed no differences in elimination half-life, clearance, or volume of distribution compared to patients with normal renal function 2, 3
Hemodialysis does not remove buprenorphine: The drug is not dialyzable due to its high lipid solubility and extensive protein binding (96%), resulting in stable plasma levels and consistent analgesia throughout dialysis sessions 3, 4, 5
Evidence from Dialysis Studies
The most definitive evidence comes from pharmacokinetic studies in dialysis patients:
In patients receiving continuous buprenorphine infusions, clearance was similar between those with normal renal function (934 ml/min) and those with renal impairment (1102 ml/min) 3
While norbuprenorphine plasma concentrations increased 4-fold and buprenorphine-3-glucuronide increased 15-fold in renal failure patients, these metabolites are minimally active and do not cause clinically significant toxicity 3
A study of 10 chronic pain patients on transdermal buprenorphine undergoing hemodialysis found no elevated plasma levels (median 0.16 ng/ml before and 0.23 ng/ml after dialysis) and no changes in pain relief, confirming that hemodialysis does not affect buprenorphine disposition 5
Guideline Recommendations
Major international guidelines consistently recommend buprenorphine as a preferred opioid for dialysis patients:
The European Society for Medical Oncology (ESMO) designates buprenorphine as the safest opioid choice in chronic kidney disease stages 4-5 (GFR <30 ml/min) or dialysis, requiring no dose reduction 1
The FDA drug label explicitly states: "No differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following IV administration" 2
Multiple guidelines classify buprenorphine alongside fentanyl as "relatively safe in renal failure" due to the absence of toxic metabolite accumulation 6, 7
Contrast with Other Opioids
Understanding why other opioids are problematic highlights buprenorphine's advantages:
Morphine and codeine must be avoided entirely in dialysis patients due to accumulation of morphine-6-glucuronide and morphine-3-glucuronide, which cause neurotoxicity, confusion, and respiratory depression 1, 6, 8
Hydromorphone requires caution because hydromorphone-3-glucuronide accumulates between dialysis sessions, causing increased pain and reduced analgesic duration 6
Meperidine is contraindicated due to accumulation of normeperidine, which causes seizures and cardiac arrhythmias 1, 6
Clinical Application
For practical use in dialysis patients:
Transdermal buprenorphine is preferred for stable chronic pain, with starting doses of 17.5-35 mcg/hour requiring no adjustment for renal function 1, 6
IV buprenorphine can be used for acute pain with initial doses of 25-50 mcg administered slowly, titrated every 5 minutes as needed 6
No dose reduction or interval extension is necessary regardless of dialysis schedule 1, 9
Important Caveat
The only consideration in dialysis patients is hepatic function, not renal function: