Chronic kidney disease as a risk factor for incident hearing loss

慢性肾病是听力损失的危险因素

• 批准号: 9605963
• 负责人: Shruti Gupta
• 金额: $ 8.12万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9605963
• 关键词: ATP phosphohydrolase; Address; Adult; Affect; Age; American; Anatomy; Animal Model; Area; Audiometry; Auditory; Bilateral Hearing Loss; Blood; Categories; Cells; Chronic; Chronic Kidney Failure; Cochlea; Communication; Creatinine; Cross-Sectional Studies; Data; Dementia; Devices; Donor person; Ear; Early Diagnosis; Early Intervention; Electrolytes; End stage renal failure; Endolymph; Enzymes; Epidemiology; Etiology; Frequencies; Functional disorder; General Hospitals; Glomerular Filtration Rate; Goals; Graft Survival; Health; Hearing; High Prevalence; Hospitals; Impaired Renal Function; Impaired cognition; Incidence; Individual; Intervention; Kidney; Kidney Diseases; Kidney Transplantation; Labyrinth; Lead; Link; Living Donors; Longitudinal Studies; Longitudinal cohort study; Massachusetts; Measurement; Measures; Mental Depression; Monitor; Na(+)-K(+)-Exchanging ATPase; Observational Study; Outcome; Participant; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physicians; Physiological; Prospective cohort study; Public Health; Pump; Pure-Tone Audiometry; Quality of life; Race; Renal function; Reporting; Risk; Risk Factors; Sensorineural Hearing Loss; Serum; Social isolation; Testing; Time; Transplant Recipients; Transplantation; Tubular formation; United States; Woman; cohort; design; experience; hearing impairment; high risk; improved; mortality; ototoxicity; portability; primary outcome; prospective; recruit; secondary analysis; sex

Project Summary Hearing loss is an exceedingly common and debilitating chronic health condition, with over 30 million individuals 12 years and older suffering from bilateral hearing loss in the United States. Auditory dysfunction has been linked to social isolation, depression, dementia, and increased mortality; however, many gaps persist in our understanding of the pathophysiology of this condition. Small observational studies have suggested there may be a link between chronic kidney disease (CKD) and hearing loss, with 36% to 77% of individuals with CKD having at least mild sensorineural hearing loss. The cochlea and the kidney share anatomic and physiologic similarities, with many of the same pumps, channels, and ATP-ases expressed in both the renal tubular cells and the inner ear. Animal models also suggest there is an inverse correlation between serum creatinine levels and Na+/K+ ATPase activity in the ear, and therefore inhibition of ATPase activity by impaired renal function may promote inner ear dysfunction. There are no longitudinal studies that have assessed the relation between chronic kidney disease and hearing loss. Furthermore, there are no data that delineate how hearing thresholds change before and after renal transplant, once a uremic state has been corrected. We therefore propose to highlight a potential causal association between hearing loss and CKD. In Aim 1, we will conduct a prospective cohort study to assess whether reduced renal function is associated with an increased risk of hearing loss. We will utilize the Epidemiology of Hearing Loss Study, a longitudinal cohort study that has assessed the incidence and progression of hearing loss. Renal function was measured at two different time points in 1847 participants, and pure tone audiometry was conducted at baseline and every 5 years thereafter. We will use baseline and subsequent measurements of estimated glomerular filtration rate (eGFR) divided into categories to compare the risk of incident hearing loss. We hypothesize that those participants with a lower baseline eGFR, and those with a rapid decline in eGFR over time, will have an increased risk of incident hearing loss. In Aim 2, we will conduct a prospective cohort study to determine the association between renal transplantation and auditory function before and after transplant. We will recruit recipients of living donor transplants (n=34) over one year at Brigham and Women's Hospital and Massachusetts General Hospital. We will then conduct pure tone audiometry testing within 30 days before the transplant is performed, and then at months 1, 3, 6, and 12 post-transplant. We hypothesize that transplant recipients will have improvement in their hearing thresholds 6 months post-transplant, as compared with pre-transplant. Collectively, these studies could allow for earlier diagnosis and intervention for those at highest risk of hearing loss, and potentially lead to significant improvements in quality of life for CKD patients.

项目摘要 听力损失是一种非常常见和令人衰弱的慢性健康状况， 在美国，12岁及以上患有双侧听力损失的人。听觉功能障碍 与社会孤立、抑郁、痴呆和死亡率增加有关;然而，许多差距仍然存在 我们对这种情况的病理生理学的理解。小型观察性研究表明 慢性肾脏疾病（CKD）和听力损失之间可能存在联系，36%至77%的人 患有至少轻度感音神经性听力损失的CKD患者。耳蜗和肾脏共享解剖学和 生理上的相似性，许多相同的泵，通道，和ATP酶表达在肾脏和肾脏。 管状细胞和内耳。动物模型也表明，血清中 耳朵中的肌酸酐水平和Na+/K+ ATP酶活性，从而抑制ATP酶活性受损 肾功能可能促进内耳功能障碍。没有纵向研究评估 慢性肾脏病与听力损失的关系此外，没有数据说明如何 一旦尿毒症状态得到纠正，肾移植前后的听阈会发生变化。我们 因此，建议强调听力损失和CKD之间的潜在因果关系。在目标1中，我们 进行一项前瞻性队列研究，以评估肾功能降低是否与 听力损失的风险。我们将利用听力损失流行病学研究，这是一项纵向队列研究， 评估听力损失的发生率和进展。在两个不同时间点测定肾功能 在1847名参与者中，在基线和此后每5年进行一次纯音测听。 我们将使用基线和后续测量的估计肾小球滤过率（eGFR）分为 听力损失的危害有哪些？我们假设那些低血糖的参与者 基线eGFR和eGFR随时间迅速下降的患者， 听力损失在目标2中，我们将进行一项前瞻性队列研究，以确定肾脏疾病与糖尿病之间的关系。 移植前后听觉功能的变化。我们将招募活体捐赠者 在布里格姆妇女医院和马萨诸塞州总医院进行了一年以上的移植（n=34）。我们 然后在移植前30天内进行纯音听力测试，然后在 移植后1、3、6和12个月。我们假设，移植受者将改善， 与移植前相比，移植后6个月的听力阈值。总的来说，这些研究 可以为听力损失风险最高的人提供早期诊断和干预，并可能导致 CKD患者生活质量的显著改善。