The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging
The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging
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DOI：
10.1681/asn.2016020154
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发表时间：
2017-01-01
影响因子：
13.6
通讯作者：
Rule, Andrew D.
中科院分区：
文献类型：
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作者：
Denic, Aleksandar;Lieske, John C.;Rule, Andrew D.
肾单位数量可能是肾脏健康的一个重要决定因素，但很难在活体中进行研究。我们评估了马约诊所（MN和AZ研究中心）和克利夫兰诊所的1638例活体供肾者。我们从捐赠前的计算机断层扫描中获得了两个肾脏的皮质体积。在肾移植时，我们获得并分析了皮质活检标本的切片，以确定非硬化性和全局硬化性肾小球的密度;肾小球总数由皮质体积x肾小球密度估计。18-29岁的供体平均每个肾脏有990，661个非硬化性肾小球和16，614个整体硬化性肾小球，在70-75岁的供体中，每个肾脏逐渐减少到520，410个非硬化性肾小球和增加到141，714个整体硬化性肾小球。在最年轻和最年长的年龄组之间，非硬化性肾小球的数量减少了48%，而皮质体积仅减少了16%，活检中全球硬化性肾小球的比例仅增加了15%。与非硬化性肾小球较少独立相关的临床特征是年龄较大、身高较矮、ESRD家族史、血清尿酸水平较高和GFR测定值较低。随着年龄的增长，肾小球硬化增加或皮质体积下降的肾单位损失的不完全代表性与全球硬化性肾小球的萎缩和重吸收以及剩余肾单位的肥大一致。总之，健康成人的肾单位数量减少与出生时肾单位禀赋减少和随后肾单位丢失的特征有关。
Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume x glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.