NSAID Use and Multidimensional Assessment of Kidney Health

NSAID 的使用和肾脏健康的多维评估

• 批准号: 10249179
• 负责人: Jonathan Amatruda
• 金额: $ 6.56万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-24 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249179
• 关键词: Acute Pain; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse effects; Albuminuria; Analgesics; Ankylosing spondylitis; Award; Benign; Biological Markers; Characteristics; Chronic Kidney Failure; Clinic; Clinical; Cohort Studies; Communities; Creatinine; Data; Data Collection; Development; Dimensions; Disease Progression; Dose; Drug Exposure; Drug usage; Drug user; Elderly; Enrollment; Exposure to; Fibrosis; Foundations; Fright; Functional disorder; Glomerular Filtration Rate; Goals; Health; Incidence; Inflammation; Injury; Injury to Kidney; Interleukin-18; Investigation; Ischemia; K-Series Research Career Programs; Kidney; Kidney Diseases; LCN2 gene; Link; Longitudinal Studies; Longitudinal cohort; Measures; Medical; Mentorship; Methods; Monitor; Non-Steroidal Anti-Inflammatory Agents; Older Population; Opioid; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Pattern; Persons; Pharmaceutical Preparations; Population; Positioning Attribute; Prospective Studies; Renal function; Renal tubule structure; Reporting; Risk; Safety; Sensitivity and Specificity; Serum; Spondylarthritis; Statistical Data Interpretation; Time; Training; Tubular formation; UMOD gene; Uncertainty; Urine; Variant; Work; adverse outcome; base; career; chronic pain; cohort; evidence base; follow-up; functional decline; glomerular filtration; glomerular function; hemodynamics; high risk; high risk population; improved; medication safety; muscle form; nephrotoxicity; novel; older patient; opioid epidemic; opioid use; post gamma-globulins; prognostic; prospective; renal damage; risk stratification; specific biomarkers; standardize measure; stem; supportive environment; true biomarker; tubular necrosis; urinary; vasoconstriction

PROJECT SUMMARY/ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics for the treatment of acute and chronic pain, but their use is limited by concerns of potential nephrotoxicity. Though some cohort studies have associated NSAID-use with adverse kidney outcomes, the reported magnitudes of these associations are variable. Accurate assessment of kidney health risks among NSAID users remains difficult, in part due to the challenge of measuring NSAID exposure and the comparison of heterogenous populations in past cohort studies. As clinicians seek alternative options for effective pain management to stem the opioid epidemic, improved understanding of the impact of NSAID use on kidney health is urgently needed to inform approaches for safe prescribing. To this end, we propose analyzing the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort, which recorded high-quality, standardized measures of NSAID use over time for each participant. Because NSAIDs are a mainstay of ankylosing spondylitis (AS) treatment, this population encompasses a range of NSAID exposure from very high intensity users to non-users over the course of up to 15 years of follow-up. These high-quality data thus allow rigorous investigation of dose and duration of NSAID exposure as possible drivers of kidney disease. Our proposed studies are a necessary step to better understanding of NSAID-associated kidney risk and to safer, evidence-based prescribing. Aim 1 will use the entire available PSOAS cohort to investigate the longitudinal association between NSAID exposure and kidney function. This Aim will improve upon past studies by (1) leveraging the granular and complete exposure data in PSOAS and (2) comparing estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C to determine the most sensitive indicator of kidney function decline in this population. Aim 1 will produce a high-quality estimate of the overall risk of NSAID- associated kidney function decline in this population and elucidate which doses, durations, and subject characteristics entail the highest risk of adverse outcomes. Aim 2 will focus on a subcohort of PSOAS participants based at UCSF and actively followed in the UCSF AS clinic to cross-sectionally measure urine biomarkers of tubulointerstitial function, injury, inflammation, and fibrosis. Aim 2 will characterize patterns of urine biomarkers corresponding to NSAID exposure. Results from this study will inform a longitudinal study of multidimensional kidney monitoring (GFR and tubulointerstitial health) to guide NSAID use that controls pain but minimizes kidney damage. These efforts can be extended to high-risk populations, including the elderly and patients with chronic kidney disease.

项目总结/摘要 非甾体类抗炎药（NSAID）是治疗急性和慢性炎症的有效镇痛药， 慢性疼痛，但它们的使用受到潜在肾毒性的限制。尽管一些队列研究 使用NSAID与肾脏不良结局相关，报告的这些相关性的程度为 变量准确评估NSAID使用者的肾脏健康风险仍然很困难，部分原因是 测量NSAID暴露的挑战和过去队列中异质性人群的比较 问题研究随着临床医生寻求有效疼痛管理的替代方案以遏制阿片类药物的流行， 迫切需要进一步了解NSAID使用对肾脏健康的影响， 安全处方 为此，我们建议分析强直性脊柱炎结局的前瞻性研究 （PSOAS）队列，该队列记录了NSAID使用随时间推移的高质量标准化测量， 参与者。由于NSAID是强直性脊柱炎（AS）治疗的主要药物， 包括从非常高强度使用者到非使用者的一系列NSAID暴露， 15年的随访。因此，这些高质量的数据允许对NSAID的剂量和持续时间进行严格的研究 暴露是肾脏疾病的可能驱动因素。 我们提出的研究是更好地了解NSAID相关肾脏风险的必要步骤 以及更安全的循证处方。目标1将使用整个可用的PSOAS队列来研究 NSAID暴露与肾功能之间的纵向关联。这一目标将改善过去的研究 通过（1）利用PSOAS中的颗粒和完整暴露数据和（2）比较估计的肾小球 滤过率（eGFR）是通过血清肌酐和胱抑素C来确定肾功能最敏感的指标 这一人群的功能下降。目标1将对NSAID的总体风险进行高质量的估计- 在该人群中相关的肾功能下降，并阐明哪些剂量，持续时间和受试者 这些特征带来了最高的不良后果风险。目标2将重点关注PSOAS的子队列 参与者基于UCSF，并在UCSF AS诊所积极随访，以横断面测量尿液 肾小管间质功能、损伤、炎症和纤维化的生物标志物。目标2将描述 对应于NSAID暴露的尿生物标志物。这项研究的结果将为以下纵向研究提供信息： 多维肾脏监测（GFR和肾小管间质健康），以指导控制疼痛的NSAID使用 但最大限度地减少了肾损伤。这些努力可以扩大到包括老年人在内的高危人群 和慢性肾病患者。

项目成果

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults.

• DOI: 10.1111/jgs.16961
• 发表时间: 2021-03
• 期刊: Journal of the American Geriatrics Society
• 影响因子: 6.3
• 作者: Amatruda JG;Katz R;Peralta CA;Estrella MM;Sarathy H;Fried LF;Newman AB;Parikh CR;Ix JH;Sarnak MJ;Shlipak MG;Health ABC Study
• 通讯作者: Health ABC Study

Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure.

• DOI: 10.1016/j.xkme.2022.100465
• 发表时间: 2022-06
• 期刊: KIDNEY MEDICINE
• 影响因子: 3.9
• 作者: Amatruda, Jonathan G.;Scherzer, Rebecca;Rao, Veena S.;Ivey-Miranda, Juan B.;Shlipak, Michael G.;Estrella, Michelle M.;Testani, Jeffrey M.
• 通讯作者: Testani, Jeffrey M.

Biomarkers of Kidney Tubule Disease and Risk of End-Stage Kidney Disease in Persons With Diabetes and CKD.

• DOI: 10.1016/j.ekir.2022.03.033
• 发表时间: 2022-07
• 期刊: KIDNEY INTERNATIONAL REPORTS
• 影响因子: 6
• 作者: Amatruda, Jonathan G.;Katz, Ronit;Sarnak, Mark J.;Gutierrez, Orlando M.;Greenberg, Jason H.;Cushman, Mary;Waikar, Sushrut;Parikh, Chirag R.;Schelling, Jeffrey R.;Jogalekar, Manasi P.;Bonventre, Joseph, V;Vasan, Ramachandran S.;Kimmel, Paul L.;Shlipak, Michael G.;Ix, Joachim H.
• 通讯作者: Ix, Joachim H.