Authors: Yang, Sisi et al.
Anesthesiology November 2025 | DOI: 10.1097/ALN.0000000000005829
This large cohort study from the UK Biobank investigated the link between chronic pain, analgesic use, and the development of chronic kidney disease (CKD) in individuals with diabetes. The analysis included over 20,000 diabetic participants who provided detailed information on seven chronic pain locations and medication use. Researchers examined long-term outcomes using multivariable Cox regression models and integrated metabolic and proteomic data to identify underlying biological pathways.
Over a median follow-up of 13.2 years, 2,589 participants developed CKD. Chronic pain was associated with an 18% higher risk of CKD (adjusted HR 1.18). Pain in the neck/shoulder, back, hip, knee, and abdominal regions significantly increased CKD risk, while headache and facial pain did not. Each additional pain site increased CKD risk by approximately 8% (HR 1.08 per site). Among those with chronic pain, opioid use further increased CKD risk (HR 1.22), whereas ibuprofen and paracetamol did not show significant associations.
Metabolomic and proteomic profiling revealed three consistent biological signals linked to pain-related CKD risk: elevated chromogranin-A, increased glycoprotein acetyls, and a reduced omega-3 to total fatty acids ratio. Protein network mapping identified TNF and EGFR as central molecular hubs mediating the observed association between multisite pain and renal dysfunction.
These findings suggest that both widespread chronic pain and opioid exposure contribute independently to kidney injury risk in diabetic individuals. The data underscore the importance of kidney-aware pain management strategies, emphasizing the potential harms of chronic opioid therapy in this population.
What You Should Know
In diabetic patients, chronic pain involving multiple body sites is a significant risk factor for CKD. Opioid use amplifies this risk, while non-opioid analgesics do not. The study identifies distinct metabolic and proteomic signatures that may explain how systemic inflammation and lipid imbalance connect chronic pain and renal decline.
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