Takashima Kohei, Hitosugi Masahito, Uno Akari, Taniura Naoko, Mukaisho Ken-Ich, Maruo Yoshihiro
Department of Legal Medicine, Shiga University of Medical Science, Shiga, 520-2192, Japan.
Department of Pediatrics, Shiga University of Medical Science, Shiga, 520-2192, Japan.
Pediatr Nephrol. 2025 May;40(5):1613-1624. doi: 10.1007/s00467-024-06644-7. Epub 2025 Jan 10.
Podocyte depletion is a critical factor in glomerulosclerosis development. While podocyte numbers per glomerulus typically decline with age in adults, they are hypothesized to increase during childhood. However, studies on podocyte number progression in childhood have been limited.
This retrospective analysis examined forensic autopsy cases of Japanese children without kidney disease, aged under 192 months, between April 2010 and March 2023. Podocytes were identified using immunostaining with an anti-transducin-like enhancer of split 4 antibody and p57. Podometric parameters were estimated using the correction factor method, allowing estimation from a single histologic section.
This study included 68 cases with a median age of 9 months (interquartile range [IQR], 4-78). All podometric parameters correlated with age. Children younger than 36 months displayed significantly fewer podocyte numbers per glomerulus (median, 517; IQR, 483-546) compared to those aged 36 months and older (median, 616; IQR, 595-649; p < 0.001). Regression analysis revealed a significant age-related increase in podocyte numbers per glomerulus in children under 36 months (slope, 3.76; p < 0.001; 95% confidence interval [CI], 2.34-5.19), but not in those aged 36 months and older (slope, 0.25; p = 0.16; 95% CI, - 0.10-0.61). Additionally, the change in the slope at 36 months was significant (p < 0.001; 95% CI, 1.02-2.49); however, this increase did not appear linked to podocyte division.
Podocyte numbers per glomerulus increased from birth until 36 months and then stabilized. These findings could facilitate the development of novel treatments for chronic kidney disease caused by glomerulosclerosis and contribute to pediatric kidney health research.
足细胞耗竭是肾小球硬化发展的关键因素。虽然在成年人中，每个肾小球的足细胞数量通常会随着年龄的增长而下降，但据推测在儿童期会增加。然而，关于儿童期足细胞数量变化的研究一直有限。
这项回顾性分析研究了2010年4月至2023年3月期间192个月以下无肾脏疾病的日本儿童的法医尸检病例。使用抗分裂泛素样增强子4抗体和p57免疫染色鉴定足细胞。使用校正因子法估计足测量参数，从而能够从单个组织学切片进行估计。
本研究纳入了68例病例，中位年龄为9个月（四分位间距[IQR]，4-78）。所有足测量参数均与年龄相关。与36个月及以上儿童（中位数，616；IQR，595-649）相比，36个月以下儿童每个肾小球的足细胞数量明显较少（中位数，517；IQR，483-546；p<0.001）。回归分析显示，36个月以下儿童每个肾小球的足细胞数量与年龄显著相关（斜率，3.76；p<0.001；95%置信区间[CI]，2.34-5.19），而36个月及以上儿童则不然（斜率，0.25；p=0.16；95%CI，-0.10-0.61）。此外，36个月时斜率的变化具有显著性（p<0.001；95%CI，1.02-2.49）；然而，这种增加似乎与足细胞分裂无关。
每个肾小球的足细胞数量从出生到36个月增加，然后稳定下来。这些发现可能有助于开发针对肾小球硬化引起的慢性肾病的新疗法，并为儿科肾脏健康研究做出贡献。
