Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension
Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension
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DOI：
10.1681/asn.2020101486
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发表时间：
2021-05-01
影响因子：
13.6
通讯作者：
Bertram, John F.
中科院分区：
文献类型：
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作者：
Haruhara, Kotaro;Sasaki, Takaya;Bertram, John F.
背景：足细胞耗竭、肾单位数目减少、衰老和高血压与肾小球硬化和慢性肾脏病有关。方法：为了调查肾单位数相对较低的健康日本人的足部计量学和肾单位数，我们对30名日本活体肾捐献者(中位年龄，57岁)的单个石蜡切片进行了足细胞特异性标记免疫组织化学染色和共聚焦显微镜图像分析。我们使用基于模型的体视学来估计足计量学，并使用增强计算机断层扫描/活检标本体视学相结合的方法来估计肾单位数目。结果：每个肾脏的非硬化性肾单位的中位数为659,000个(四分位数范围[IQR]，564,000-825,000)。足细胞数和密度的中位数分别为每丛518个(IQR，428-601)和219个(IQR，180-253)/106亩·m~3，这些数值与以前报道的其他小种相似。每个肾脏的足细胞总数(通过非硬化性肾小球的个体数量乘以每个肾小球的足细胞数量)为3.76亿(IQR，2.59-4.49亿)，在供者之间变化7.4倍。平均而言，这些健康肾脏平均每个肾脏每年损失563万个足细胞，其中大部分损失与全球肾小球硬化导致的肾小球损失有关，而不是健康肾小球的足细胞损失。高血压与较低的足细胞密度和较大的足细胞体积有关，与年龄无关。结论：对单个肾脏中肾单位、足细胞和其他足细胞参数的估计为了解这些参数、年龄和肾脏高血压之间的关系提供了新的见解。这种方法在评估肾脏的健康和疾病方面可能有相当大的价值。
Background: Podocyte depletion, low nephron number, aging, and hypertension are associated with glomerulosclerosis and CKD. However, the relationship between podometrics and nephron number has not previously been examined.Methods: To investigate podometrics and nephron number in healthy Japanese individuals, a population characterized by a relatively low nephron number, we immunostained single paraffin sections from 30 Japanese living-kidney donors (median age, 57 years) with podocyte-specific markers and analyzed images obtained with confocal microscopy. We used model-based stereology to estimate podometrics, and a combined enhanced-computed tomography/biopsy-specimen stereology method to estimate nephron number.Results: The median number of nonsclerotic nephrons per kidney was 659,000 (interquartile range [IQR], 564,000-825,000). The median podocyte number and podocyte density were 518 (IQR, 428-601) per tuft and 219 (IQR, 180-253) per 106 mu m3, respectively; these values are similar to those previously reported for other races. Total podocyte number per kidney (obtained by multiplying the individual number of nonsclerotic glomeruli by podocyte number per glomerulus) was 376 million (IQR, 259-449 million) and ranged 7.4-fold between donors. On average, these healthy kidneys lost 5.63 million podocytes per kidney per year, with most of this loss associated with glomerular loss resulting from global glomerulosclerosis, rather than podocyte loss from healthy glomeruli. Hypertension was associated with lower podocyte density and larger podocyte volume, independent of age.Conclusions: Estimation of the number of nephrons, podocytes, and other podometric parameters in individual kidneys provides new insights into the relationships between these parameters, age, and hypertension in the kidney. This approach might be of considerable value in evaluating the kidney in health and disease.