{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:23:32Z","timestamp":1778678612810,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 \u03b1-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 \u00b1 3.76 years. Results: The results of this study revealed that CCSs exhibited significantly higher levels of soluble \u03b1-Klotho compared to healthy peers (1331.4 \u00b1 735.5 pg\/mL vs. 566.43 \u00b1 157.7 pg\/mL, p &lt; 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 &lt; 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of \u03b1-Klotho and FGF23, and nephro- and cardiotoxicity. Conclusions: In conclusion, this preliminary cross-sectional study revealed elevated levels of \u03b1-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated \u03b1-Klotho protein levels among CCSs warrants further investigation.<\/jats:p>","DOI":"10.3390\/jcm13102968","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:23Z","timestamp":1715947343000},"page":"2968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating Levels of Soluble \u03b1-Klotho and FGF23 in Childhood Cancer Survivors: Lack of Association with Nephro- and Cardiotoxicity\u2014A Preliminary Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Kacper","family":"Koz\u0142owski","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-8040","authenticated-orcid":false,"given":"Katarzyna","family":"Kono\u0144czuk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-2145","authenticated-orcid":false,"given":"Katarzyna","family":"Muszy\u0144ska-Ros\u0142an","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-015X","authenticated-orcid":false,"given":"Beata","family":"\u017belazowska-Rutkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Laboratory Diagnostics, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-8866","authenticated-orcid":false,"given":"Katarzyna","family":"Taranta-Janusz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Nephrology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Werbel","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Pathology and Newborn Intensive Care, J\u0119drzej \u015aniadecki Independent Public Healthcare Center\u2014Regional Hospital, 15-027 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryna","family":"Krawczuk-Rybak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-7953","authenticated-orcid":false,"given":"Eryk","family":"Latoch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-274 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1056\/NEJMsa060185","article-title":"Chronic Health Conditions in Adult Survivors of Childhood Cancer","volume":"355","author":"Oeffinger","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","first-page":"CD008944","article-title":"Early and Late Adverse Renal Effects after Potentially Nephrotoxic Treatment for Childhood Cancer","volume":"3","author":"Kooijmans","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00467-017-3662-z","article-title":"Late Renal Toxicity of Treatment for Childhood Malignancy: Risk Factors, Long-Term Outcomes, and Surveillance","volume":"33","author":"Skinner","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1007\/s00467-005-1839-3","article-title":"Renal Function during and after Treatment for Acute Lymphoblastic Leukemia in Children","volume":"20","author":"Wysocka","year":"2005","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"B\u0119dzichowska, A., Jobs, K., Kloc, M., Bujnowska, A., and Kalicki, B. (2021). The Assessment of the Usefulness of Selected Markers in the Diagnosis of Chronic Kidney Disease in Children. Biomark. Insights, 16.","DOI":"10.1177\/11772719211011173"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000380970","article-title":"Klotho\/FGF23 Axis in CKD","volume":"Volume 185","author":"Tsuchiya","year":"2015","journal-title":"Contributions to Nephrology Chronic Kidney Diseases\u2014Recent Advances in Clinical and Basic Research"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3322\/caac.21731","article-title":"Cancer Treatment and Survivorship Statistics, 2022","volume":"72","author":"Miller","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/CIRCULATIONAHA.115.020406","article-title":"Shared Risk Factors in Cardiovascular Disease and Cancer","volume":"133","author":"Koene","year":"2016","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1056\/NEJMra1100265","article-title":"Cardiovascular Toxic Effects of Targeted Cancer Therapies","volume":"375","author":"Moslehi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chang, K., Li, Y., Qin, Z., Zhang, Z., Wang, L., Yang, Q., and Su, B. (2023). Association between Serum Soluble \u03b1-Klotho and Urinary Albumin Excretion in Middle-Aged and Older US Adults: NHANES 2007\u20132016. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020637"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1210\/er.2013-1079","article-title":"Molecular Basis of Klotho: From Gene to Function in Aging","volume":"36","author":"Xu","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R23","DOI":"10.1530\/JME-20-0178","article-title":"FGF23 Signalling and Physiology","volume":"66","author":"Ho","year":"2021","journal-title":"J. Mol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Casta\u00f1eda, J.R., Rodelo-Haad, C., Pendon-Ruiz de Mier, M.V., Martin-Malo, A., Santamaria, R., and Rodriguez, M. (2020). Klotho\/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease. Toxins, 12.","DOI":"10.3390\/toxins12030185"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41569-023-00903-0","article-title":"FGF23 and Klotho at the Intersection of Kidney and Cardiovascular Disease","volume":"21","author":"Edmonston","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ewendt, F., Feger, M., and F\u00f6ller, M. (2020). Role of Fibroblast Growth Factor 23 (FGF23) and \u03b1Klotho in Cancer. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.601006"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s40200-019-00398-y","article-title":"Oncogenic Osteomalacia and Metastatic Breast Cancer: A Case Report and Review of the Literature","volume":"18","author":"Savva","year":"2019","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Latoch, E., Kono\u0144czuk, K., Taranta-Janusz, K., Muszy\u0144ska-Ros\u0142an, K., Sawicka, M., Wasilewska, A., and Krawczuk-Rybak, M. (2021). Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors. J. Clin. Med., 10.","DOI":"10.3390\/jcm10225279"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00280-020-04164-3","article-title":"Urine NGAL and KIM-1: Tubular Injury Markers in Acute Lymphoblastic Leukemia Survivors","volume":"86","author":"Latoch","year":"2020","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1038\/s41388-022-02440-5","article-title":"The Role of \u03b1-Klotho in Human Cancer: Molecular and Clinical Aspects","volume":"41","author":"Ligumsky","year":"2022","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"931746","DOI":"10.3389\/fphar.2022.931746","article-title":"The Controversy of Klotho as a Potential Biomarker in Chronic Kidney Disease","volume":"13","author":"Yu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","article-title":"The Klotho Proteins in Health and Disease","volume":"15","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, Q., Su, W., Shen, Z., and Wang, R. (2018). Correlation between Soluble \u03b1-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis. Biomed. Res. Int., 2018.","DOI":"10.1155\/2018\/9481475"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1136\/jim-2017-000560","article-title":"Plasma S-Klotho Is Related to Kidney Function and Predicts Adverse Renal Outcomes in Patients with Advanced Chronic Kidney Disease","volume":"66","author":"Liu","year":"2018","journal-title":"J. Investig. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/ckj\/sfz085","article-title":"Performance of Soluble Klotho Assays in Clinical Samples of Kidney Disease","volume":"13","author":"Neyra","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s11255-020-02510-1","article-title":"Lower Circulating Soluble Klotho Level Is Associated with Increased Risk of All-Cause Mortality in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis","volume":"52","author":"Charoenngam","year":"2020","journal-title":"Int. Urol. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000506380","article-title":"Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease","volume":"10","author":"Yang","year":"2020","journal-title":"Cardiorenal Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jamacardio.2016.1445","article-title":"Association of Fibroblast Growth Factor 23 With Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study","volume":"1","author":"Mehta","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/eurheartj\/ehy815","article-title":"Data-Driven Discovery and Validation of Circulating Blood-Based Biomarkers Associated with Prevalent Atrial Fibrillation","volume":"40","author":"Chua","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"899667","DOI":"10.3389\/fcvm.2022.899667","article-title":"Relationship between Serum Growth Differentiation Factor 15, Fibroblast Growth Factor-23 and Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis","volume":"9","author":"Tan","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1158\/1055-9965.EPI-13-0036","article-title":"Glomerular Function Time Trends in Long-Term Survivors of Childhood Cancer: A Longitudinal Study","volume":"22","author":"Mulder","year":"2013","journal-title":"Cancer Epidemiol. Biomarkers Prev."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2968\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:10Z","timestamp":1760107450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["jcm13102968"],"URL":"https:\/\/doi.org\/10.3390\/jcm13102968","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,17]]}}}