Non-SteroidAl Impact on Kidney Disease Study (NSAIDS)

非类固醇对肾脏疾病的影响研究 (NSAIDS)

• 批准号: 10655205
• 负责人: Michelle M Estrella
• 金额: $ 70.41万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655205
• 关键词: Absence of pain sensation; Adult; Adverse effects; Analgesics; Benign; Biological Markers; Blood; Chronic; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Collaborations; Creatinine; Development; Dimensions; Dose; Drug Exposure; Drug toxicity; Drug usage; Early Diagnosis; Elderly; Essential Drugs; Fibrosis; Fright; Fumarates; Future; Generations; Glomerular Filtration Rate; Goals; HIV Infections; Health; Hypertension; Incidence; Inflammation; Injury; Injury to Kidney; Kidney; Kidney Diseases; Learning; Measures; Monitor; Muscle; Non-Steroidal Anti-Inflammatory Agents; Opioid; Outcome; Pain; Pain management; Participant; Patients; Pattern; Persons; Pharmaceutical Preparations; Population; Prevalence; Proteins; Renal function; Renal tubule structure; Research; Risk; Risk Factors; Role; Safety; Serum; Severities; Site; Specificity; Spondylarthritis; Tenofovir; Time; Toxic effect; Tubular formation; United States; Urine; Work; chronic pain; chronic pain management; cohort; comorbidity; diagnostic panel; disorder risk; drug action; effective therapy; evidence base; experience; follow-up; high risk; high risk population; improved; insight; nephrotoxicity; novel; opioid epidemic; prognostication; renal artery; renal damage; risk mitigation; tool; treatment choice; vasoconstriction

ABSTRACT The prevalence of chronic pain among adults in the United States now exceeds 20% and is even higher among older adults and those with multiple comorbid conditions. As clinicians have increasingly learned to avoid opiates for chronic pain, non-steroidal anti-inflammatory drugs (NSAIDs) have an essential role as effective analgesics. Unfortunately, the threat of kidney toxicity from NSAIDs limits their use for pain control, and there are no options available to mitigate that risk during treatment. As a result, clinicians largely avoid using NSAIDs in persons who either have chronic kidney disease (CKD) or are at high risk for developing CKD, regardless of their severity of pain. The premise of this proposal is that NSAID effects on the kidneys can be monitored through a biomarker guided strategy, and that nephrotoxicity can be detected early among the subset who would experience deleterious impact on their kidneys. The primary objective of this proposal will be to build an NSAID Kidney Monitoring Panel from urine and blood biomarkers of kidney tubule health that will identify the specific sites of NSAID toxicity, distinguish NSAID-induced changes on the kidney, and forecast the impact on subsequent kidney function declines. Current monitoring for NSAID-related kidney toxicity still relies on serum creatinine (SCr), which is insensitive for early detection, lacks specificity for true kidney injury, and does not measure tubulointerstitial health, the major site of NSAID action and injury. Without a better strategy, clinicians will continue withholding NSAIDs from patients in chronic pain. Our research team has experience in deploying a broad panel of urine and blood biomarkers of kidney tubular function, injury and tubulointerstitial inflammation that enables both the sensitivity to detect early kidney damage and the specificity to distinguish patterns that are most consistent with a distinct medication effect. We will apply this strategy among two populations at high risk for developing NSAID nephrotoxicity. To best characterize the impact of high-dose NSAID use, we will evaluate the UCSF Axial Spondyloarthritis Cohort (Aim 1), as patients with this condition have few other treatment options and are also largely free of other kidney risk factors. Second, we will collaborate with the Chronic Renal Insufficiency Cohort (CRIC) to determine the effects of NSAID initiation and discontinuation on kidney health in this very high-risk group with moderate-to-severe CKD (Aim 2). In Aim 3, we will integrate the findings from each setting to determine the set of biomarkers that best captures chronic NSAID exposure, dynamic changes in longitudinal NSAID use, and risks for longitudinal kidney function trajectories. This research will unquestionably yield tremendous insights into the incidence and patterns of kidney tubulointerstitial injury from NSAID use in these two distinct populations. We are optimistic that our findings will guide future development of an NSAID Kidney Monitoring Panel that will improve the safe and effective treatment of pain across the spectrum of kidney disease risk.

抽象的 美国成年人中慢性疼痛的患病率现在超过20％，甚至更高 在老年人和有多个合并症的人中。随着临床医生越来越多地学会 避免阿片类药物治疗慢性疼痛，非甾体类抗炎药（NSAID）具有重要作用 有效的镇痛药。不幸的是，NSAIDS肾脏毒性的威胁限制了其用于控制​​疼痛的使用， 并且没有任何选择可以在治疗期间减轻这种风险。结果，临床医生在很大程度上避免 在患有慢性肾脏疾病（CKD）的人中使用NSAID，或者有高风险 CKD，无论他们的痛苦严重程度如何。该提议的前提是NSAID对肾脏的影响可以 通过生物标志物引导的策略来监测，并且可以在 子集将对肾脏产生有害影响。该提议的主要目的是 用尿液和肾小管健康的血液生物标志物建立NSAID肾脏监测面板 确定NSAID毒性的特定部位，区分NSAID诱导的肾脏变化，并预测 对随后肾功能的影响下降。 当前对NSAID相关肾脏毒性的监测仍然依赖于血清肌酐（SCR）， 对早期发现不敏感，缺乏对真正肾脏损伤的特异性，并且不测量肾小管间隙 健康，NSAID行动和伤害的主要地点。没有更好的策略，临床医生将继续扣留 慢性疼痛患者的NSAID。我们的研究团队有部署大量尿液的经验 以及肾小管功能，损伤和微管炎的血液生物标志物，这两者都可以 敏感性检测早期肾脏损伤和区分最一致的模式的特异性 具有明显的药物效果。我们将在两个高风险的人群中应用这种策略 NSAID肾毒性。为了最好地表征大剂量NSAID使用的影响，我们将评估UCSF 轴向脊椎关节炎队列（AIM 1），因为患有这种疾病的患者几乎没有其他治疗选择，并且是 也很大程度上没有其他肾脏危险因素。其次，我们将与慢性肾功能不全合作 同类（CRIC）确定NSAID启动和中断对肾脏健康的影响 具有中度至重度CKD的高风险组（AIM 2）。在AIM 3中，我们将整合每个设置的发现 为了确定最能捕获慢性NSAID暴露的生物标志物集，动态变化 纵向NSAID的使用和纵向肾功能轨迹的风险。 这项研究无疑将对肾脏的发病率和模式产生深刻的见解 NSAID在这两个不同的种群中使用NSAID造成的肾小管间质损伤。我们对我们的发现会感到乐观 指导NSAID肾脏监测面板的未来开发，该面板将改善安全有效 治疗肾脏疾病风险的疼痛。