Circulating Levels of Soluble α-Klotho and FGF23 in Childhood Cancer Survivors: Lack of Association with Nephro- and Cardiotoxicity-A Preliminary Study

Background/Objectives: The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum alpha-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. Methods: This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 +/- 3.76 years. Results: The results of this study revealed that CCSs exhibited significantly higher levels of soluble alpha-Klotho compared to healthy peers (1331.4 +/- 735.5 pg/mL vs. 566.43 +/- 157.7 pg/mL, p < 0.0001), while no significant difference was observed in their FGF23 levels. Within the participant cohort, eight individuals (12%) demonstrated a reduced estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m2. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of alpha-Klotho and FGF23, and nephro- and cardiotoxicity. Conclusions: In conclusion, this preliminary cross-sectional study revealed elevated levels of alpha-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated alpha-Klotho protein levels among CCSs warrants further investigation.