When managing pain in patients with compromised renal function, selecting an opioid analgesic with a safer metabolic profile is crucial to avoid accumulation of active metabolites that can cause toxicity.

- Morphine and codeine are primarily metabolized in the liver to active metabolites that are excreted renally.
- In patients with impaired renal function, these metabolites can accumulate, leading to increased risk of respiratory depression, sedation, and neurotoxicity.

- Hydromorphone also has active metabolites that are renally excreted and may accumulate in renal impairment, although to a lesser extent than morphine.

In contrast, fentanyl is metabolized mainly by the liver through CYP3A4 to inactive metabolites and has minimal renal excretion. Due to this pharmacokinetic profile, fentanyl does not accumulate in patients with renal dysfunction, making it the preferred opioid for pain management in this population.

Key points:
- Morphine and codeine: Active metabolites accumulate in renal impairment → increased toxicity risk
- Hydromorphone: Active metabolites present, cautious use required
- Fentanyl: Metabolized to inactive metabolites, minimal renal excretion → safer in renal failure

Therefore, fentanyl is preferred for pain management in patients with compromised renal function due to its safer metabolic and excretion profile.

Reference: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition, Volume 1, Chapter 25 (Opioid Analgesics)