Research Paper Volume 12, Issue 21 pp 21730—21746

Frailty modifies the association between opioid use and mortality in chronic kidney disease patients with diabetes: a population-based cohort study

Szu-Ying Lee1, , Jui Wang2, , Chia-Ter Chao3,4,5, , Kuo-Liong Chien2, , Jenq-Wen Huang1, , on behalf of the COGENT study group (COhort of GEriatric Nephrology in NTUH),

  • 1 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
  • 2 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
  • 3 Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei, Taiwan
  • 4 Geriatric and Community Medicine Research Center, National Taiwan University Hospital BeiHu Branch, Taipei, Taiwan
  • 5 Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan

Received: March 7, 2020       Accepted: August 14, 2020       Published: November 7, 2020
How to Cite

Copyright: © 2020 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The prevalence of chronic pain in patients with chronic kidney disease (CKD) and diabetes mellitus is high and correlates with higher frailty risk, but satisfactory pain control frequently fails, necessitating opioid initiation. We aimed to examine whether opioid use affected their outcomes and whether such a relationship was modified by frailty. From the longitudinal cohort of diabetes patients (n = 840,000), we identified opioid users with CKD (n = 26,029) and propensity score-matched them to opioid-naïve patients in a 1:1 ratio. We analyzed the associations between opioid use and long-term mortality according to baseline frailty status, defined by the modified FRAIL scale. Among all, 20.3% did not have any FRAIL items, while 57.2%, 20.6%, and 1.9% had 1, 2, and at least 3 positive FRAIL items, respectively. After 4.2 years, 16.4% died. Cox proportional hazard regression showed that opioid users exhibited an 18% higher mortality risk (HR 1.183, 95% CI 1.13-1.24) with a dose- and duration-responsive relationship, compared to opioid-naive ones. Furthermore, the mortality risk posed by opioids was observed only in CKD patients without frailty but not in those with frailty. In conclusion, opioid use increased mortality among patients with CKD, while this negative outcome influence was not observed among frail ones.


aDCSI: adapted diabetes complications severity index; CCI: Charlson comorbidity index; CI: confidence interval; CKD: chronic kidney disease; DDD: defined daily dosage; DM: diabetes mellitus; DOPPS: Dialysis Outcomes and Practice Patterns Study; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; HR: hazard ratio; IANA: International Association of Nutrition and Aging; LCDP: Longitudinal Cohort of Diabetes Patients; NSAID: non-steroidal anti-inflammatory drug.