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Kidney Week

Abstract: SA-PO0702

Expression of Fibroblast Growth Factor 23 (FGF-23) and α-KLOTHO in Normal Human Kidney Development and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Racetin, Anita, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Bajt, Patricija, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Kelam, Nela, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Pavlović, Nikola, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Todorović, Petar, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Jelinčić Korčulanin, Marinela, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Martino, Jeremiah, Pace University, New York, New York, United States
  • Filipovic, Natalija, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
  • Vukojevic, Katarina, Sveuciliste u Splitu Medicinski fakultet, Split, Split-Dalmatia County, Croatia
Background

FGF23 and its co-receptor α-KLOTHO regulate mineral balance in adult kidneys, however their roles in kidney development and CAKUT remain poorly understood.

Methods

Human fetal kidney tissues of 14 conceptuses were used as controls and compared with 17 CAKUT samples. Sections were stained with the immunofluorescence method with FGF23 and α -KLOTHO markers.

Results

FGF23 was strongly expressed in the cortex of control fetal kidneys (CTRL), particularly in Bowman’s capsule and the distal tubules, while in the medulla it was mainly found in the collecting ducts and thick loop of Henle. Its expression was higher in the cortex than in the medulla (p < 0.0001) and decreased with fetal age (p < 0.01, p < 0.0001). Furthermore, α-KLOTHO was expressed in the same regions as FGF23 except for Bowman’s capsule. Unlike FGF23, α-KLOTHO expression increased significantly during fetal development (p < 0.05, p < 0.0001) and became more prominent in the cortex at later stages (p < 0.05, p < 0.01). In CAKUT samples, FGF23 expression was significantly reduced in horseshoe (p < 0.01) and duplex kidneys (p < 0.001), but remained unchanged in hypoplastic and dysplastic kidneys. α-KLOTHO expression did not differ significantly across CAKUT subtypes.

Conclusion

Based on our results, we suggest that altered FGF23 expression in CAKUT contributes to disease pathogenesis and may represent a potential therapeutic target.

Immunofluorescence staining of human fetal kidneys with FGF23 antibody (a–c) shows its localization in dysplastic (21st dw), horseshoe (26th dw), and duplex kidneys (30th dw), indicated by arrows. Images were taken at 40× magnification (scale bar: 60 µm). Histogram (d) presents FGF23 area percentages in CTRL, DK, HK, HYP, and DYS kidneys (mean ± SD; Kruskal–Wallis and Dunn’s tests, p < 0.01, p < 0.001).

Digital Object Identifier (DOI)