Integrated Mineral Metabolism Treatment Strategies in Patients on Dialysis

透析患者的综合矿物质代谢治疗策略

• 批准号: 9219542
• 负责人: Julia J Scialla
• 金额: $ 51.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9219542
• 关键词: Admission activity; Advanced Practice Nurse; Adverse effects; Advocate; Age; Agonist; Area; Biochemical; Biological; Bone Diseases; Calcium; Calcium Binding; Calcium-Sensing Receptors; Cardiovascular Diseases; Caring; Characteristics; Clinic; Clinical; Clinical Data; Clinical Practice Guideline; Clinical Trials; Combined Modality Therapy; Data; Data Collection; Data Element; Dialysis patients; Dialysis procedure; Dose; Dropout; Drug toxicity; End stage renal failure; Equipoise; Event; Evidence based practice; Feedback; Focus Groups; Fracture; Goals; Guidelines; Hemodialysis; Hormones; Hospitalization; Hospitals; Hypercalcemia; Hypocalcemia result; Intention; Intervention; Interview; Investigation; Kidney; Knowledge; Laboratories; Lead; Link; Medical Records; Metabolism; Methods; Minerals; Modeling; Morbidity - disease rate; Nausea; Nutritionist; Observational Study; Outcome; PTH gene; Patient Care; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Phosphorus; Physician Assistants; Physicians; Physiological; Placebos; Process; Provider; Quality of life; Randomized; Recommendation; Regimen; Risk; Risk Factors; Structural Models; Testing; Time; Translating; United States; Update; Variant; Vitamin D; adverse outcome; alternative treatment; base; cardiovascular risk factor; care delivery; clinical practice; clinical predictors; clinically relevant; common treatment; comparative effectiveness; design; effectiveness trial; fibroblast growth factor 23; gastrointestinal; health related quality of life; improved; mortality; patient population; peer; preclinical study; prevent; prospective; randomized trial; success; treatment choice; treatment strategy

PROJECT SUMMARY Patients with end stage kidney disease on dialysis have deranged mineral metabolism, including often severe changes in calcium, phosphorus, parathyroid hormone and the phosphorus-regulatory hormone fibroblast growth factor 23. Pre-clinical studies strongly suggest that these mineral metabolism abnormalities may directly increase risk of common morbidities in this group including cardiovascular and bone disease. These potential effects in pre-clinical studies are supported by observational studies in patients linking mineral metabolism abnormalities with morbidity and mortality. Although treatment of mineral metabolism derangements is widespread in practice, there are no definitive trials demonstrating the best approaches to prevent common adverse outcomes in patients on dialysis such as accelerated mortality, cardiovascular disease and frequent hospital admissions. This application will utilize clinical practice data as well as patient and provider engagement to design needed trials and overcome prior barriers to trial success such as high rates of mineral metabolism treatment discontinuation and change. Because (1) multiple classes of pharmacologic agents are available to treat mineral metabolism abnormalities; and, (2) guidelines advocate broad ranges for biochemical parameters, such as phosphorus and parathyroid hormone, providers have many choices for their overall approach to mineral metabolism treatment and demonstrate substantial variation in approaches. This proposal will leverage real-world practice data derived from detailed medical records and linked administrative claims in a large population of patients treated with in-center hemodialysis to understand alternative treatment strategies and compare their outcomes. Aim 1 will define common treatment strategies that incorporate different pharmacologic agent combinations, doses and mineral metabolite target values (i.e., integrated strategies), and identify predictors of different prescribing practices in this area using discrete choice models. Aim 2 will evaluate the prospective association of integrated treatment strategies with adverse clinical outcomes, including mortality, cardiovascular disease events, fracture, hospitalization and health-related quality of life. Unique data elements, such as frequently updated medication and clinical data and facility clustering are well-suited to marginal structural modeling and instrumental variable methods to better account for potential confounding. In Aim 3, focus groups and directed interviews with patients and dialysis care providers will be used to deeply evaluate underlying reasons for frequent discontinuation and change of the treatment strategy that plagued prior trials. Ultimately, these studies will identify alternative strategies that are practical in real-world settings, associated with the most optimal clinical outcomes and sustainable through optimized care delivery, thereby solidifying the evidence-base for practice in this pervasive aspect of dialysis care. Additionally, results will select intervention and comparator strategies, from among many possibilities, that may be most effective and sustainable for further testing in definitive trials.

项目总结