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

## TL;DR

This study examines how opioid doses increase over time in patients with chronic kidney disease and finds that dose escalation is common, especially in the first six months.

## Contribution

The study provides real-world data on opioid dose escalation patterns in patients with varying levels of kidney function.

## Key findings

- Opioid dose escalation to ≥50 MME/day occurred in 7.3% of patients, with similar rates across kidney function levels.
- Patients with reduced kidney function had significantly lower risks of escalating to higher opioid doses.
- Most dose escalation occurred within the first six months of starting opioids.

## Abstract

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.

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

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.

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.

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.