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: 9766079
• 负责人: Shruti Gupta
• 金额: $ 8.6万
• 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/9766079
• 关键词: ATP phosphohydrolase; Address; Adult; Affect; Age; American; Anatomy; Animal Model; Area; 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; Graft Survival; Health; Hearing; Hearing Tests; 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; deaf; design; experience; health goals; hearing impairment; hearing loss risk; hearing threshold; high risk; improved; living kidney donor; mortality; ototoxicity; portability; post-transplant; 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 听力损失是一种极为普遍的慢性健康状况，超过3000万 在美国，患有双侧听力损失的个人12岁及以上。听觉功能障碍 与社会隔离，抑郁，痴呆和死亡率增加有关；但是，许多差距仍然存在 在我们对这种疾病的病理生理学的理解中。小型观察研究表明 慢性肾脏疾病（CKD）与听力损失之间可能存在联系，其中36％至77％ CKD至少具有轻度的感觉性听力损失。耳蜗和肾脏共享解剖学和 生理相似性，许多相同的泵，通道和ATP-ass在肾脏中表达 管状细胞和内耳。动物模型还表明血清之间存在逆相关性 肌酐水平和耳朵中的Na+/K+ ATPase活性，因此受到抑制ATPase活性 肾功能可能促进内耳功能障碍。没有纵向研究评估 慢性肾脏疾病与听力丧失之间的关系。此外，没有数据可以描述 肾脏移植前后，听力阈值一旦纠正了尿液状态。我们 因此，建议强调听力损失与CKD之间的潜在因果关系。在AIM 1中，我们将 进行一项前瞻性队列研究，以评估降低的肾功能是否与增加有关 听力损失的风险。我们将利用听力损失研究的流行病学，这是一项纵向队列研究 评估了听力损失的发生率和进展。在两个不同的时间测量肾功能 1847年的参与者的积分和纯音调测定法在基线和此后每5年进行了一次。 我们将使用基线和随后的估计肾小球过滤率（EGFR）的测量 比较事件听力损失风险的类别。我们假设那些较低的参与者 基线EGFR以及EGFR随着时间的流逝而迅速下降的人，发生事件的风险会增加 听力损失。在AIM 2中，我们将进行一项前瞻性队列研究，以确定肾脏之间的关联 移植之前和之后的移植和听觉功能。我们将招募活着捐助者的接收者 在杨百翰，妇女医院和马萨诸塞州综合医院的一年内移植（n = 34）。我们 然后，将在进行移植之前的30天内进行纯音调测试，然后在 移植后第1、3、6和12个月。我们假设移植接受者将有所改善 与移植前相比，移植后6个月他们的听力阈值。总的来说，这些研究 可以允许对听力损失风险最高的人进行较早的诊断和干预，并有可能导致 CKD患者的生活质量大大改善。