Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
J Am Soc Nephrol. 2021 May 3;32(5):1187-1199. doi: 10.1681/ASN.2020101486. Epub 2021 Feb 24.
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.
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.
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 10m, 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.
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.
足细胞耗竭、肾单位数量减少、衰老和高血压与肾小球硬化和 CKD 有关。然而，足细胞参数与肾单位数量之间的关系尚未被研究。
为了研究健康日本人的足细胞参数和肾单位数量，我们对 30 名日本活体供肾者（中位年龄 57 岁）的石蜡切片进行了足细胞特异性标志物免疫染色，并分析了共聚焦显微镜获得的图像。我们使用基于模型的体视学法来估计足细胞参数，并使用增强 CT/活检标本体视学法来估计肾单位数量。
每例肾脏非硬化肾单位的中位数为 659,000（四分位距[IQR]，564,000-825,000）。每个足突的中位数足细胞数和足细胞密度分别为 518（IQR，428-601）/簇和 219（IQR，180-253）/10μm；这些值与其他种族的报道相似。每个肾脏的总足细胞数（通过将非硬化肾小球的个体数量乘以每个肾小球的足细胞数获得）为 3.76 亿（IQR，2.59-4.49 亿），在供体之间的范围为 7.4 倍。平均而言，这些健康肾脏每年每个肾脏损失 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更大的足细胞体积有关，与年龄无关。
估计个体肾脏的肾单位、足细胞和其他足细胞参数数量为这些参数与年龄和高血压在肾脏中的关系提供了新的见解。这种方法在评估健康和疾病中的肾脏可能具有重要价值。
