Continuous increase in podocyte numbers in the first 36 months of life-insights from forensic autopsies in Japanese children.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.