The Severity of Carotid Calcifications, but Not Fibroblast Growth Factor 23, Is Associated with Mortality in Hemodialysis: A Single Center Experience
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Foreman, K.J.; Marquez, N.; Dolgert, A.; Fukutaki, K.; Fullman, N.; McGaughey, M.; Pletcher, M.A.; Smith, A.E.; Tang, K.; Yuan, C.W.; et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: Reference and alternative scenarios for 2016–40 for 195 countries and territories. Lancet 2018, 392, 2052–2090. [Google Scholar] [CrossRef]
- Düsing, P.; Zietzer, A.; Goody, P.R.; Hosen, M.R.; Kurts, C.; Nickenig, G.; Jansen, F. Vascular pathologies in chronic kidney disease: Pathophysiological mechanisms and novel therapeutic approaches. J. Mol. Med. 2021, 99, 335–348. [Google Scholar] [CrossRef] [PubMed]
- Bellasi, A.; Di Lullo, L.; Russo, D.; Ciarcia, R.; Magnocavalo, M.; Lavalle, C.; Di Iorio, B.R. Predictive value of measures of vascular calcification burden and progression for risk of death in incident to dialysis patients. J. Clin. Med. 2021, 10, 376. [Google Scholar] [CrossRef]
- Singh, A.; Tandon, S.; Tandon, C. An update on vascular calcification and potential therapeutics. Mol. Biol. Rep. 2021, 48, 887–896. [Google Scholar] [CrossRef] [PubMed]
- Prié, D. FGF23 and cardiovascular risk. Ann. Endocrinol. 2021, 82, 141–143. [Google Scholar] [CrossRef] [PubMed]
- Wanner, C.; Schuchhardt, J.; Bauer, C.; Brinker, M.; Kleinjung, F.; Vaitsiakhovich, T. Risk prediction modeling for cardiorenal clinical outcomes in patients with non-diabetic CKD using US nationwide real-world data. BMC Nephrol. 2025, 26, 8. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.X.; Tang, R.N.; Wang, L.T.; Liu, B.C. Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease. Cell Prolif. 2021, 54, e12980. [Google Scholar] [CrossRef] [PubMed]
- Viegas, C.; Araujo, N.; Marreiros, C.; Simes, D. The interplay between mineral metabolism, vascular calcification and inflammation in chronic kidney disease (CKD): Challenging old concepts with new facts. Aging 2019, 11, 4274–4299. [Google Scholar] [CrossRef] [PubMed]
- Hortells, L.; Sur, S.; St. Hilarie, C. Cell phenotype transitions in cardiovascular calcification. Front. Cardiovasc. Med. 2018, 5, 27. [Google Scholar] [CrossRef]
- Moldovan, D.; Moldovan, I.; Rusu, C.; Racasan, S.; Patiu, I.M.; Brumboiu, A.; Bondor, C.; Parvu, L.; Kacso, I.; Orasan, R.; et al. Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: What is the relationship between them? Int. Urol. Nephrol. 2011, 43, 1179–1186. [Google Scholar] [CrossRef]
- Ketteler, M.; Evenepoel, P.; Holden, R.M.; Isakova, T.; Jørgensen, H.S.; Komaba, H.; Wong, J. Chronic kidney disease–mineral and bone disorder: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2025, 107, 405–423. [Google Scholar] [CrossRef]
- Hannemann, A.; Nauck, M.; Völzke, H.; Weidner, H.; Platzbecker, U.; Hofbauer, L.C.; Baschant, U. Interactions of anemia, FGF-23, and bone in healthy adults—Results from the Study of Health in Pomerania (SHIP). J. Clin. Endocrinol. Metab. 2021, 106, e288–e299. [Google Scholar] [CrossRef] [PubMed]
- Lang, F.; Leibrock, C.; Pandyra, A.A.; Stournaras, C.; Wagner, A.; Föller, M. Phosphate Homeostasis, Inflammation and the Regulation of FGF-23. Kidney Blood Press. Res. 2018, 43, 1742–1748. [Google Scholar] [CrossRef]
- Mendoza, J.M.; Isakova, T.; Cai, X.; Bayes, L.Y.; Faul, C.; Scialla, J.J.; Townsend, R.R. Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease. Kidney Int. 2017, 91, 711–719. [Google Scholar] [CrossRef] [PubMed]
- Titan, S.M.; Zatzm, R.; Graciolli, F.G.; Dos Reis, L.M.; Barros, R.T.; Jorgetti, V.; Moysés, R.M. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin. J. Am. Soc. Nephrol. 2011, 6, 241–247. [Google Scholar] [CrossRef] [PubMed]
- Moldovan, D.; Moldovan, I.; Rusu, C.; Kacso, I.; Patiu, I.M.; Gherman-Caprioara, M. FGF-23, vascular calcification, and cardiovascular diseases in chronic hemodialysis patients. Int Urol. Nephrol. 2014, 46, 121–128. [Google Scholar] [CrossRef] [PubMed]
- Maahs, E.; Schwartz, A.; Berezowitz, A.; Davis, S.; Guzman, R.J. An ultrasound-based femoral artery calcification score. J. Vasc. Surg. Cases Innov. Tech. 2024, 10, 101381. [Google Scholar] [CrossRef] [PubMed]
- Valero, C.; Macías, J.G. Atherosclerosis, vascular calcification and osteoporosis. Med. Clínica 2025, 164, e13–e20. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Li, W.; Song, F.; Wang, L.; Fu, Q.; Cao, S.; Lu, Z. Carotid atherosclerosis detected by ultrasonography: A national Cross-Sectional study. J. Am. Heart Assoc. 2018, 7, e008701. [Google Scholar] [CrossRef] [PubMed]
- Mizuiri, S.; Nishizawa, Y.; Doi, T.; Yamashita, K.; Shigemoto, K.; Usui, K.; Masaki, T. Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis. Ren. Fail. 2021, 43, 371–380. [Google Scholar] [CrossRef]
- Asicioglu, E.; Velioglu, A.; Arikan, H.; Koc, M.; Tuglular, S.; Ozener, C. Baseline carotid intima media thickness is associated with cardiovascular morbidity and mortality in peritoneal dialysis patients. Ther. Apher. Dial. 2021, 25, 962–969. [Google Scholar] [CrossRef] [PubMed]
- Kusic Milicevic, J.; Vidakovic, R.; Markovic, R.; Andjelkovic Apostolovic, M.; Korac, M.; Trbojevic Stankovic, J.; Dragovic, G. Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of haemodialysis. Ther. Apher. Dial. 2022, 6, 64–70. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.H.; Liou, H.H.; Wu, C.K. Moderate-severe aortic arch calcification and high serum alkaline phosphatase co-modify the risk of cardiovascular events and mortality among chronic hemodialysis patients. Ren. Fail. 2025, 47, 2449572. [Google Scholar] [CrossRef] [PubMed]
- Gutierrez, O.M.; Mannstadt, M.; Isakova, T.; Rauh-Hain, J.A.; Tamez, H.; Shah, A.; Smith, K.; Lee, H.; Thadhani, R.; Jüppner, H.; et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N. Engl. J. Med. 2008, 359, 584–592. [Google Scholar] [CrossRef]
- Alderson, H.V.; Ritchie, J.P.; Middleton, R.; Larsson, A.; Larsson, T.E.; Kalra, P.A. FGF-23 and Osteoprotegerin but not Fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3–5. Nephrology 2016, 21, 566–573. [Google Scholar] [CrossRef]
- Salam, S.; Gallagher, O.; Gossiel, F.; Paggiosi, M.; Eastell, R.; Khwaja, A. Vascular calcification relationship to vascular biomarkers and bone metabolism in advanced chronic kidney disease. Bone 2021, 143, 115699. [Google Scholar] [CrossRef] [PubMed]
- Block, G.A.; Chertow, G.M.; Cooper, K.; Xing, S.; Fouqueray, B.; Halperin, M.; Danese, M.D. Fibroblast growth factor 23 as a risk factor for cardiovascular events and mortality in patients in the EVOLVE trial. Hemodial. Int. 2021, 25, 78–85. [Google Scholar] [CrossRef] [PubMed]
- Coban, M.; Yilmaz, U.; Suleyman, D.; Asilturk, E.; Sozer, Y.; Bekir, E.R.; Ellidag, H.Y. Intact Fibroblast Growth Factor 23 and peripheral vascular complications in patients on hemodialysis. Dicle Tıp Dergisi 2020, 47, 66–73. [Google Scholar] [CrossRef]
- De Jong, M.A.; Eisenga, M.F.; van Ballegooijen, A.J.; Beulens, J.W.; Vervloet, M.G.; Navis, G.; De Borst, M.H. Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: The Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Nephrol. Dial. Transplant. 2021, 36, 121–128. [Google Scholar] [CrossRef]
- Olauson, H.; Qureshi, A.R.; Miyamoto, T.; Barany, P.; Heimburger, O.; Lindholm, B.; Stenvinkel, P.; Larsson, T.E. Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: Are gender and cardiovascular disease confounding the relationship? Nephrol. Dial. Transplant. 2010, 25, 3033–3038. [Google Scholar] [CrossRef] [PubMed]
- Fitzpatrick, J.; Kim, E.D.; Sozio, S.M.; Jaar, B.G.; Estrella, M.M.; Monroy-Trujillo, J.M.; Parekh, R.S. Calcification biomarkers, subclinical vascular disease, and mortality among multiethnic dialysis patients. Kidney Int. Rep. 2020, 5, 1729–1737. [Google Scholar] [CrossRef]
- Bouma-de Krijger, A.; de Roij van Zuijdewijn, C.L.; Nubé, M.J.; Grooteman, M.P.; Vervloet, M.G.; CONTRAST Study Group. Change in FGF23 concentration over time and its association with all-cause mortality in patients treated with haemodialysis or haemodiafiltration. Clin. Kidney J. 2021, 14, 891–897. [Google Scholar] [CrossRef]
- Palupi-Baroto, R.; Hermawan, K.; Murni, I.K.; Nurlita, T.; Prihastuti, Y.; Puspitawati, I.; Tandri, C.C.; Ambarsari, C.G. Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease. BMC Nephrol. 2024, 25, 369. [Google Scholar] [CrossRef] [PubMed]
- Nishizawa, Y.; Hosoda, Y.; Horimoto, A.; Omae, K.; Ito, K.; Higuci, C.; Sakura, H.; Nitta, K.; Ogawa, T. Fibroblast growth factor 23 (FGF23) level is associated with ultrafiltration rate in patients on hemodialysis. Heart Vessel. 2020, 36, 414–423. [Google Scholar] [CrossRef] [PubMed]
- Edmonston, D.; Grabner, A.; Wolf, M. FGF23 and klotho at the intersection of kidney and cardiovascular disease. Nat. Rev. Cardiol. 2024, 21, 11–24. [Google Scholar] [CrossRef]
- Kacso, I.M.; Potra, A.R.; Bondor, C.I.; Moldovan, D.; Rusu, C.; Patiu, I.M.; Kacso, G. Adiponectin predicts cardiovascular events in diabetes dialysis patients. Clin. Biochem. 2015, 48, 860–865. [Google Scholar] [CrossRef] [PubMed]
- Kanda, E.; Lopes, M.B.; Tsuruya, K.; Hirakata, H.; Iseki, K.; Karaboyas, A.; Bieber, b.; Jacobson, S.J.; Dasgupta, I.; Robinson, B.M. The combination of malnutrition-inflammation and functional status limitations is associated with mortality in hemodialysis patients. Sci. Rep. 2021, 11, 1582. [Google Scholar] [CrossRef]
- Huang, J.; Hao, J.; Luo, H.; Chen, L.; Luo, H.; Liu, H.; Wang, P. Construction of a C-reactive protein-albumin-lymphocyte index-based prediction model for all-cause mortality in patients on maintenance hemodialysis. Ren. Fail. 2025, 47, 2444396. [Google Scholar] [CrossRef]
- Sánchez-Duffhues, G.; García de Vinuesa, A.; van de Pol, V.; Geerts, M.E.; de Vries, M.R.; Janson, S.G.; van Dam, H.; Lindeman, J.H.; Goumans, M.J.; Ten Dijke, P. Inflammation induces endothelial-to-mesenchymal transition and promotes vascular calcification through downregulation of BMPR2. J. Pathol. 2019, 247, 333–346. [Google Scholar] [CrossRef] [PubMed]
- Donate-Correa, J.; Martín-Núñez, E.; Hernández-Carballo, C.; González-Luis, A.; Mora-Fernández, C.; Martín-Olivera, A.; Navarro-González, J.F. FGF23 as a potential pathophysiological factor in peripheral arterial disease associated with chronic kidney disease. Int. J. Mol. Sci. 2024, 25, 5457. [Google Scholar] [CrossRef] [PubMed]
- Izzo, C.; Secondulfo, C.; Bilancio, G.; Visco, V.; Virtuoso, N.; Migliarino, S.; Vecchione, C. Chronic kidney disease with mineral bone disorder and vascular calcification: An overview. Life 2024, 14, 418. [Google Scholar] [CrossRef] [PubMed]
- Gu, L.; Xia, Z.; Qing, B.; Wang, W.; Chen, H.; Wang, J.; Yuan, Y. Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: Evidence from NHANES (2001–2018). Front. Immunol. 2024, 15, 1338025. [Google Scholar] [CrossRef] [PubMed]
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024, 105, S117–S314. Available online: https://kdigo.org/guidelines/ckd-evaluation-and-management/ (accessed on 22 January 2025). [CrossRef] [PubMed]
Deceased (49 Patients) | Survivors (39 Patients) | p | |
---|---|---|---|
Age (years) | 63 (59–72) | 56 (46–64) | 0.003 |
HD vintage (months) | 47 (29–64) | 49 (29.5–68) | 0.628 |
Gender, males no. (%) | 27 (55.1) | 18 (46.2) | 0.404 |
Diabetes, no. (%) | 17 (34.7) | 3 (7.7) | 0.003 |
HTN, no. (%) | 38 (77.6) | 25 (64.1) | 0.165 |
FGF-23 (pg/mL) | 42.30 (23.10–72.70) | 41.70 (20.95–70.90) | 0.592 |
VC score | 4 (1–6) | 0 (0–2) | <0.001 |
URR | 72.32 (69.57–79.45) | 77.33 (69.63–80.65) | 0.183 |
spKt/V | 1.46(1.39–1.63) | 1.58 (1.40–1.66) | 0.183 |
Bicarbonate (mEq/L) | 24 (22.7–25.6) | 22.9 (20.5–24.6) | 0.084 |
K (mEq/L) | 4.48 ± 0.64 | 4.72 ± 0.55 | 0.067 |
Ca (mg/dL) | 9.09 ± 0.65 | 9.07 ± 0.67 | 0.898 |
P (mg/dL) | 4.34 ± 1.10 | 4.57 ± 1.54 | 0.427 |
ALP (U/L) | 78.68 (64.13–99.56) | 67.75 (45.22–103.84) | 0.957 |
iPTH (pg/mL) | 212.25 (144.75–547.65) | 273.4 (160.95–536) | 0.332 |
Hb (g/dL) | 11.3 (10.6–12) | 11.4 (10.5–12.35) | 0.072 |
Ferritin (ng/mL) | 498.51 (303.45–791.35) | 586.22 (402.46–816.45) | 0.784 |
CRP (mg/dL) | 0.80 (0.35–2.02) | 0.47 (0.28–1.04) | 0.035 |
Albumin (g/dL) | 3.75 (3.57–3.94) | 3.96 (3.80–4.08) | 0.005 |
Creatinine (mg/dL) | 8.20 ± 1.98 | 8.73 ± 2.53 | 0.265 |
Ca in HD solution | 1.5 (1.25–1.5) | 1.5 (1.25–1.5) | 0.854 |
Treatment with Ca salts, no. (%) | 30 (61.2) | 17 (43.6) | 0.099 |
Sevelamer, no. (%) | 10 (20.4) | 10 (25.6) | 0.561 |
Vitamin D Treatment, no. (%) | 10 (20.4) | 10 (25.6) | 0.561 |
Cardiovascular diseases, no. (%) | 23 (46.9) | 4 (10.3) | <0.001 |
All-Cause Mortality | Cardiovascular Mortality | |||
---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | |
Age (years) | 1.04 (1.01–1.06) | 0.002 | 1.03 (1.00–1.06) | 0.019 |
HD vintage (months) | 0.99 (0.99–1.00) | 0.577 | 0.99 (0.99–1.00) | 0.785 |
Gender (males) | 0.77 (0.43–1.35) | 0.361 | 0.67 (0.34–1.33) | 0.254 |
Diabetes | 2.74 (1.50–5.01) | 0.001 | 2.56 (1.25–5.24) | 0.01 |
HTN | 1.41 (0.72–2.77) | 0.307 | 1.11 (0.52–2.39) | 0.779 |
FGF-23 (pg/mL) | 1.00 (0.99–1.00) | 0.676 | 1.00 (0.99–1.00) | 0.841 |
Carotid VC score | 1.24 (1.11–1.39) | <0.001 | 1.22 (1.07–1.40) | 0.003 |
URR | 0.98 (0.96–1.00) | 0.119 | 0.97 (0.95–0.99) | 0.026 |
spKt/V | 0.48 (0.19–1.20) | 0.119 | 0.33 (0.12–0.87) | 0.026 |
Bicarbonate (mEq/L) | 1.07 (0.98–1.16) | 0.092 | 1.05 (0.95–1.16) | 0.342 |
K (mEq/L) | 0.65 (0.39–1.06) | 0.085 | 1.03 (0.58–1.81) | 0.917 |
Ca (mg/dL) | 1.01 (0.64–1.60) | 0.948 | 1.27 (0.73–2.23) | 0.395 |
P (mg/dL) | 0.88 (0.71–1.09) | 0.263 | 0.89 (0.69–1.16) | 0.411 |
ALP (U/L) | 1.00 (0.99–1.00) | 0.945 | 1.00 (0.99–1.00) | 0.590 |
iPTH (pg/mL) | 1.00 (0.99–1.00) | 0.210 | 1.00 (0.99–1.00) | 0.399 |
Hb (g/dL) | 0.85 (0.70–1.04) | 0.117 | 0.89 (0.71–1.13) | 0.375 |
Ferritin (ng/mL) | 1.00 (0.99–1.00) | 0.788 | 1.00 (1.00–1.00) | 0.514 |
CRP (mg/dL) | 1.24 (1.10–1.38) | <0.001 | 1.27 (1.13–1.44) | <0.001 |
Albumin (g/dL) | 0.41 (0.23–0.71) | 0.002 | 0.58 (0.27–1.24) | 0.162 |
Creatinine (mg/dL) | 0.95 (0.84–1.06) | 0.371 | 1.03 (0.89–1.19) | 0.660 |
Ca in HD solution | 1.03 (0.67–1.58) | 0.890 | 0.79 (0.45–1.30) | 0.330 |
Treatment with Ca salts—patients (%) | 1.50 (0.84–2.68) | 0.164 | 1.17 (0.59–2.31) | 0.644 |
Sevelamer—patients (%) | 0.69 (0.34–1.39) | 0.303 | 0.71 (0.31–1.64) | 0.430 |
Vitamin D Treatment—patients (%) | 0.75 (0.37–1.50) | 0.419 | 0.76 (0.33–1.75) | 0.521 |
Cardiovascular diseases | 2.84 (1.61–5.01) | <0.001 | 2.38 (1.20–4.72) | 0.013 |
All-Cause Mortality | ||
---|---|---|
HR (95% CI) | p | |
Age (years) | 1.02 (0.99–1.05) | 0.185 |
FGF-23 (pg/mL) | 1.00 (0.99–1.00) | 0.090 |
Diabetes | 2.35 (1.19–4.64) | 0.014 |
VC score | 1.19 (1.01–1.39) | 0.031 |
K | 0.94 (0.51–1.73) | 0.860 |
Bicarbonate | 1.09 (0.97–1.23) | 0.122 |
Albumin | 0.66 (0.31–1.43) | 0.297 |
CRP | 1.28 (1.12–1.46) | <0.001 |
Cardiovascular diseases | 1.34 (0.67–2.68) | 0.400 |
Cardiovascular Mortality | ||
---|---|---|
HR (95% CI) | p | |
Age (years) | 1.02 (0.98–1.06) | 0.221 |
FGF-23 (pg/mL) | 1.00 (0.99–1.00) | 0.432 |
Diabetes | 2.16 (1.03–4.55) | 0.041 |
VC score | 1.22 (1.02–1.47) | 0.028 |
CRP | 1.36 (1.18–1.56) | <0.001 |
URR | 0.95 (0.93–0.99) | 0.009 |
Cardiovascular diseases | 1.12 (0.51–2.44) | 0.762 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Moldovan, D. The Severity of Carotid Calcifications, but Not Fibroblast Growth Factor 23, Is Associated with Mortality in Hemodialysis: A Single Center Experience. Diseases 2025, 13, 73. https://doi.org/10.3390/diseases13030073
Moldovan D. The Severity of Carotid Calcifications, but Not Fibroblast Growth Factor 23, Is Associated with Mortality in Hemodialysis: A Single Center Experience. Diseases. 2025; 13(3):73. https://doi.org/10.3390/diseases13030073
Chicago/Turabian StyleMoldovan, Diana. 2025. "The Severity of Carotid Calcifications, but Not Fibroblast Growth Factor 23, Is Associated with Mortality in Hemodialysis: A Single Center Experience" Diseases 13, no. 3: 73. https://doi.org/10.3390/diseases13030073
APA StyleMoldovan, D. (2025). The Severity of Carotid Calcifications, but Not Fibroblast Growth Factor 23, Is Associated with Mortality in Hemodialysis: A Single Center Experience. Diseases, 13(3), 73. https://doi.org/10.3390/diseases13030073