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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要听力损失是一种极其常见且令人衰弱的慢性健康状况，超过 3000 万人患有听力损失。美国 12 岁及以上患有双侧听力损失的个人。听觉障碍与社会孤立、抑郁、痴呆和死亡率增加有关；然而，仍然存在许多差距在我们对这种情况的病理生理学的理解中。小型观察研究表明慢性肾病 (CKD) 与听力损失之间可能存在关联，36% 至 77% 的人患有至少轻度感音神经性听力损失的 CKD。耳蜗和肾脏具有相同的解剖结构和结构生理学上的相似性，有许多相同的泵、通道和 ATP 酶在肾和肾中表达管状细胞和内耳。动物模型还表明血清与耳朵中的肌酐水平和 Na+/K+ ATP 酶活性，因此受损的 ATP 酶活性受到抑制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之间的关系。此外，没有数据说明如何一旦尿毒症状态得到纠正，肾移植前后的听力阈值就会发生变化。我们因此，建议强调听力损失与 CKD 之间的潜在因果关系。在目标 1 中，我们将进行一项前瞻性队列研究来评估肾功能下降是否与肾功能增加相关听力损失的风险。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。在两个不同时间测量肾功能对 1847 名参与者进行了评分，并在基线时和此后每 5 年进行一次纯音测听。我们将使用估计肾小球滤过率 (eGFR) 的基线和后续测量值分为类别来比较突发性听力损失的风险。我们假设那些具有较低水平的参与者基线 eGFR 以及 eGFR 随着时间的推移快速下降的患者，发生事件的风险将会增加听力损失。在目标 2 中，我们将进行一项前瞻性队列研究，以确定肾功能与肾功能之间的关联。移植前后的听觉功能。我们将招募活体捐赠者的接受者布莱根妇女医院和马萨诸塞州总医院一年内进行了移植手术 (n=34)。我们然后将在移植前 30 天内进行纯音听力测试，然后在移植后第 1、3、6 和 12 个月。我们假设移植受者的病情将会有所改善与移植前相比，移植后 6 个月的听力阈值。总的来说，这些研究可以为那些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 患者的生活质量显着改善。