Chronic kidney disease as a risk factor for incident hearing loss

项目摘要 听力损失是一种非常常见的慢性健康疾病，超过3000万人 在美国，12岁及以上患有双侧听力损失的个人。听觉功能障碍 与社会隔离、抑郁、痴呆症和死亡率增加有关；然而，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。小规模的观察性研究表明 慢性肾脏疾病(CKD)可能与听力损失有关，36%到77%的人 CKD至少有轻度感音神经性听力损失。耳蜗和肾脏具有共同的解剖和 生理上的相似性，许多相同的泵、通道和ATP酶在两个肾脏中表达 肾小管细胞和内耳。动物模型也表明，血清与 耳肌肌酸水平和Na~+/K~+-ATPase活性，从而抑制损伤的ATPase活性 肾功能可能促进内耳功能障碍。目前还没有纵向研究来评估 慢性肾脏疾病与听力损失的关系此外，没有数据描述如何 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，建议强调听力损失和CKD之间的潜在因果联系。在目标1中，我们将 进行一项前瞻性队列研究，以评估肾功能降低是否与 有听力损失的风险。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。在两个不同的时间测量肾功能 1847名受试者，在基线及以后每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 分类以比较事故听力损失的风险。我们假设那些较低年龄的参与者 基线EGFR和那些EGFR随着时间的推移迅速下降的人，发生事故的风险将会增加 听力损失。在目标2中，我们将进行一项前瞻性队列研究，以确定肾脏与 移植前后的听觉功能。我们将招募活体捐赠者的接受者 在布里格姆妇女医院和马萨诸塞州综合医院进行了一年以上的移植(n=34)。我们 然后在移植前30天内进行纯音测听测试，然后在 移植后1、3、6、12个月。我们假设移植受者在 分别于移植后6个月和移植前进行听阈测定。总的来说，这些研究 可以对听力损失风险最高的人进行更早的诊断和干预，并可能导致 显著改善慢性肾脏病患者的生活质量。

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.