Quantitative analysis of intrarenal nerve‐associated profiles in the human foetal kidney between 14 and 30 gestational weeks: An S100 immunohistochemical study

Abstract Quantitative data on the spatial development of intrarenal S100‐positive nerve‐associated profiles in human foetal kidneys remain limited, despite the established importance of renal nerves. Building on the previously published semiquantitative observations, this study aimed to generate a quantitative, compartment‐resolved map of S100‐positive nerve‐associated profiles in human foetal kidneys. Formalin‐fixed, paraffin‐embedded human foetal kidney specimens ranging from 14 to 30 gestational weeks were analysed using S100 immunohistochemistry. Based on gestational age, specimens were divided into three groups: ≤18 gestational weeks (G1, n=6), 19–24 gestational weeks (G2, n=6), and ≥ 25 gestational weeks (G3, n=6). Cortical maturation was assessed by measuring nephrogenic zone and maturation zone thickness and calculating the cortical maturation index (CMI). Morphometric analysis of cortical S100‐positive nerve‐associated profiles was performed using digital image analysis. Distribution patterns of S100‐positive profiles were assessed qualitatively. Group‐wise analysis demonstrated significantly lower cortical S100‐positive area in G1 compared with G2 and G3 (median: 985 μm 2 vs. 1733 μm 2 and 2400 μm 2 , respectively; p < 0.001). Cortical S100‐positive area increased significantly with gestational age and foetal weight and showed an inverse correlation with CMI ( ρ = −0.410, p < 0.001), indicating parallel progression of S100‐positive area and cortical maturation. In multivariate linear regression analyses, cortical S100‐positive area remained independently associated with gestational age ( β = 125.0, p = 0.006) and foetal weight ( β = 1.50, p = 0.006), explaining 57.6% of the variance (adjusted R 2 = 0.485). Perivascular localisation was the most frequently observed distribution pattern, while juxtaglomerular and intraglomerular patterns were also identified, including in the earliest gestational‐age group. This study provides the first quantitative, compartment‐resolved analysis of intrarenal nerve‐associated profiles in the human foetal kidney. Cortical S100‐positive area increases with gestational age in parallel with cortical maturation and shows a predominantly perivascular distribution, consistent with a neurovascular co‐development model and establishing a morphological framework for future functional studies of renal innervation.