Patterns of opioid dose escalation in patients with chronic kidney disease initiated on opioids for the treatment of non-cancer pain

PLoS One. 2026 Mar 20;21(3):e0345309. doi: 10.1371/journal.pone.0345309. eCollection 2026.

ABSTRACT

BACKGROUND: Pain management in chronic kidney disease (CKD) is challenging due to altered drug metabolism, impaired excretion, and higher opioid toxicity risk. Despite this, opioids are commonly prescribed, yet real-world data on dose escalation in CKD remain limited.

OBJECTIVE: To investigate patterns and timing of opioid dose escalation to ≥50 and ≥90 MME/day among new opioid users across kidney function levels.

METHODS: This population-based cohort study used data from the Stockholm Creatinine Measurements (SCREAM) project linking diagnoses, prescriptions, and laboratory records. Adult new opioid users (no prior opioid in 12 months) from 2012-2021 were categorized by baseline eGFR (≥60, 30-59, < 30 mL/min/1.73m²). Opioids were identified using ATC codes, and daily doses (MME/day) were calculated based on strength, quantity, and equianalgesic ratios. Fine-Gray competing-risks regression assessed time to dose escalation (≥50 and ≥90 MME/day), accounting for death as a competing event.

RESULTS: Of 81,987 adult new opioid users, 5,987 (7.3%) escalated to ≥50 MME/day comprising 7.4%, 6.8%, and 8.1% of patients with eGFR ≥ 60, 30-59, and <30 mL/min/1.73m², respectively. For ≥90 MME/day, 2,067 (2.5%) escalated, 2.5%, 2.3%, and 2.9% across the same eGFR categories. Competing risks regression showed significantly lower risks of escalation among patients with reduced eGFR levels. For ≥50 MME/day, the sub distribution hazard ratios (SHRs) were 0.67 (95% CI: 0.56-0.81, p < 0.001) for eGFR 30-59 and 0.64 (95% CI: 0.42-0.99, p = 0.043) for those with eGFR < 30.For ≥90 MME/day, SHRs were 0.57 (95% CI: 0.43-0.75, p < 0.001)and 0.31(95% CI: 0.15-0.65, p = 0.002), respectively. Most escalation occurred within six months, with minimal increase thereafter.

CONCLUSION: Opioid dose escalation occurred across all eGFR levels, underscoring the need for cautious, individualized prescribing and close monitoring, especially in patients with reduced kidney function.

PMID:41860838 | DOI:10.1371/journal.pone.0345309