Authors: Yang S et al.
Journal: Anesthesiology, December 9, 2025. DOI: 10.1097/ALN.0000000000005829
Summary
This large prospective cohort study examined the relationship between chronic pain patterns, analgesic use, and the development of chronic kidney disease (CKD) in individuals with diabetes, while also exploring associated metabolic and proteomic signatures. Given the high prevalence of chronic pain in diabetes and the known vulnerability of renal function in this population, the authors sought to clarify whether pain burden itself—and its treatment—contributes to long-term kidney risk.
Using data from more than 20,000 participants with diabetes in the UK Biobank, the investigators evaluated both site-specific and multisite chronic pain across seven anatomic regions. Over a median follow-up of more than 13 years, chronic pain was independently associated with a higher risk of incident CKD. Pain involving the neck/shoulder, back, hip, knee, and abdominal regions was associated with increased risk, whereas headache and facial pain were not.
A clear dose–response relationship emerged with multisite pain: each additional painful site further increased CKD risk. Among participants with chronic pain, opioid use was associated with a significantly higher risk of CKD, while ibuprofen and paracetamol use were not independently associated with incident kidney disease after adjustment.
Multiomics analyses identified consistent metabolic and proteomic alterations linked to CKD risk in patients with chronic pain, including elevated chromogranin-A, increased inflammatory glycoprotein acetyls, and a reduced omega-3 fatty acid ratio. Network analyses highlighted inflammatory and growth signaling pathways, with tumor necrosis factor and epidermal growth factor receptor as central nodes.
Overall, the findings suggest that chronic pain burden and opioid use may reflect or contribute to systemic processes that accelerate kidney disease in diabetes, underscoring the importance of renal-conscious pain management strategies.
Key Points
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Chronic pain in diabetes is associated with an increased risk of developing chronic kidney disease.
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Multisite chronic pain shows a dose-dependent relationship with CKD risk.
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Pain in the back, neck/shoulder, hip, knee, and abdomen is associated with higher CKD risk.
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Opioid use, but not ibuprofen or paracetamol, is linked to increased CKD risk among patients with chronic pain.
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Metabolic and proteomic signatures suggest inflammatory and growth-factor–mediated mechanisms.
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Findings highlight the need for careful analgesic selection and long-term renal risk consideration in diabetic patients with chronic pain.
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