Frequency of Hypophosphatemia Following Ferric Carboxymaltose Treatment and Associated Factors: A Single-Center Retrospective Study

Öz

Ferrik karboksimaltoz (FCM) tedavisi uygulanan hastalarda hipofosfatemi gelişme sıklığını, şiddetini ve ilişkili klinik-laboratuvar faktörleri araştırmaktır. Kırklareli Eğitim ve Araştırma Hastanesi Dahiliye Polikliniklerinde 1 Ocak–31 Aralık 2025 tarihleri arasında FCM tedavisi alan 18 yaş üstü 140 hastanın verileri retrospektif olarak incelendi. Tedavi öncesi ve sonrası serum fosfat, kalsiyum, kreatinin, hemoglobin, ferritin, D vitamini ve PTH düzeyleri değerlendirildi. Hipofosfatemi gelişimini öngören bağımsız faktörler univaryat ve multivaryat lojistik regresyon analizleri ile belirlendi. Hastaların 122'si (%87,1) kadın olup yaş ortalaması 45,8 ± 16,9 yıldı. FCM tedavisi sonrasında 81 hastada (%57,9) hipofosfatemi gelişti. Multivaryat analizde bazal serum fosfat düzeyi hipofosfatemi için tek bağımsız prediktör olarak belirlendi (OR: 0,365; %95 GA: 0,179–0,741; p=0,005). ROC analizinde bazal fosfat için optimal eşik değer 3,20 mg/dL olarak saptandı (AUC: 0,664). Orta-ağır hipofosfatemi grubundaki hastaların %82,4'ünde miyalji, halsizlik ve kramp gibi kas semptomları gelişti. FCM tedavisi hastaların yarısından fazlasında hipofosfatemiye yol açmaktadır. Tedavi öncesi serum fosfat düzeyi düşük olan ve yüksek doz FCM alan hastalar semptomatik ve orta-ağır hipofosfatemi açısından daha yüksek risk taşımaktadır. Bu hastalarda rutin fosfat izlemi hasta güvenliği açısından kritik önem taşımaktadır. 

Anahtar Kelimeler

• ferric carboxymaltose
• hypophosphatemia
• intravenous iron
• FGF-23
• iron deficiency anemia

Etik Beyan

Ethics Committee Approval: The study was approved by the Kırklareli University Non-Interventional Clinical Research Ethics Committee (Date: 05.01.2026; Protocol No: P20250076; Decision No: 12). Informed Consent: The authors declared that signed informed consent was not obtained from the cases because the study was retrospective. Conflict of Interest Statement: The authors declare that there is no conflict of interest. Funding and Acknowledgement Statement: The authors declare that they received no financial support for this study.

Ferrik Karboksimaltoz Tedavisini Takiben Gelişen Hipofosfateminin Sıklığı ve İlişkili Faktörler: Tek Merkezli Retrospektif Çalışma

Öz

This study aimed to investigate the frequency and severity of hypophosphatemia and the associated clinical and laboratory factors in patients receiving ferric carboxymaltose (FCM) treatment. Data from 140 patients aged over 18 years who received FCM treatment in the Internal Medicine Outpatient Clinics of Kırklareli Training and Research Hospital between January 1 and December 31, 2025, were retrospectively reviewed. Serum phosphate, calcium, creatinine, haemoglobin, ferritin, vitamin D, and parathyroid hormone (PTH) levels were evaluated before and after treatment. Independent factors predicting the development of hypophosphatemia were determined using univariate and multivariate logistic regression analyses. Of the patients, 122 (87.1%) were female, and the mean age was 45.8 ± 16.9 years. Hypophosphatemia developed in 81 patients (57.9%) following FCM treatment. In the multivariate analysis, baseline serum phosphate level was identified as the only independent predictor of hypophosphatemia (OR: 0.365; 95% CI: 0.179–0.741; p=0.005). ROC analysis determined the optimal cut-off value for baseline phosphate as 3.20 mg/dL (AUC: 0.664). Muscle symptoms such as myalgia, fatigue, and cramps developed in 82.4% of patients in the moderate-to-severe hypophosphatemia group.FCM treatment leads to hypophosphatemia in more than half of patients. Patients with low pre-treatment serum phosphate levels and those receiving high-dose FCM are at higher risk for symptomatic and moderate-to-severe hypophosphatemia. Routine phosphate monitoring in these patients is of critical importance for patient safety.

Anahtar Kelimeler

• ferrik karboksimaltoz
• hipofosfatemi
• intravenöz demir
• FGF-23
• demir eksikliği anemisi

Etik Beyan

Etik Kurul Onayı: Çalışma Kırklareli Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır. (Tarih : 05.01.2026 Protokol No: P20250076, Karar No: 12) Onam: Yazarlar retrospektif bir çalışma olduğu için olgulardan imzalı onam almadıklarını beyan etmişlerdir. Çıkar Çatışması Bildirimi: Yazarlar çıkar çatışması olmadığını beyan etmişlerdir. Destek ve Teşekkür Beyanı: Yazarlar bu çalışma için finansal destek almadıklarını beyan etmişlerdir.

Kaynakça

1. 1. Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18(7):435-50.
2. 2. Bock MA, Brown EG, Zhang L, Tanner C. Association of motor and nonmotor symptoms with health-related quality of life in a large online cohort of people with Parkinson disease. Neurology. 2022;98(22):e2194-203.
3. 3. Heimrich KG, Schönenberg A, Santos-García D, Mir P, Prell T. The impact of nonmotor symptoms on health-related quality of life in Parkinson’s disease: a network analysis approach. J Clin Med. 2023;12(7):2573.
4. 4. Chaudhuri KR, Martinez-Martin P, Schapira AHV, Stocchi F, Sethi K, Odin P, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord. 2006;21(7):916-23.
5. 5. Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord. 2007;22(13):1901-11.
6. 6. Chaudhuri KR, Schrag A, Weintraub D, Rizos A, Rodriguez-Blazquez C, Mamikonyan E, et al. The Movement Disorder Society Nonmotor Rating Scale: initial validation study. Mov Disord. 2020;35(1):116-33.
7. 7. van Wamelen DJ, Rota S, Schrag A, Rizos A, Martinez-Martin P, Weintraub D, et al. Characterization of non-motor fluctuations using the Movement Disorder Society Non-Motor Rating Scale. Mov Disord Clin Pract. 2022;9(7):932-40.
8. 8. Garon M, Rojo-Albuin JM, Chaudhuri KR, Rizos A, Rodriguez-Blazquez C, Mamikonyan E, et al. Conversion between NMSS and MDS-NMS in Parkinson’s disease. Mov Disord. 2025;40(5):813-20.

9. 9. Van Calster B, McLernon DJ, van Smeden M, Wynants L, Steyerberg EW, Bossuyt PMM, et al. Calibration: the Achilles heel of predictive analytics. BMC Med. 2019;17(1):230.
10. 10. Collins GS, Dhiman P, Ma J, Schlussel MM, Archer L, Van Calster B, et al. Evaluation of clinical prediction models (part 1): from development to external validation. BMJ. 2024;384:e074819.
11. 11. Riley RD, Archer L, Snell KIE, Ensor J, Dhiman P, Martin GP, et al. Evaluation of clinical prediction models (part 2): how to undertake an external validation study. BMJ. 2024;384:e074820.
12. 12. Böke A, Hacker H, Chakraborty M, Baumeister-Lingens L, Vöckel J, Koenig J, et al. Observer-independent assessment of content overlap in mental health questionnaires: large language model-based study. JMIR AI. 2025;4:e79868.
13. 13. Pincus T, Callahan LF. Depression scales in rheumatoid arthritis: criterion contamination in interpretation of patient responses. Patient Educ Couns. 1993;20(2-3):133-43.
14. 14. Akbostanci MC, Bayram E, Yilmaz V, Rzayev S, Özkan S, Tokcaer AB, et al. Turkish standardization of Movement Disorders Society Unified Parkinson’s Disease Rating Scale and Unified Dyskinesia Rating Scale. Mov Disord Clin Pract. 2018;5(1):54-9.
15. 15. Aydemir Ö. Hastane Anksiyete ve Depresyon Ölçeği Türkçe formunun geçerlilik ve güvenilirlik çalışması. Türk Psikiyatri Dergisi. 1997;8(4):280-7.
16. 16. Koçak AT, Arslan S. Validity and reliability of the Turkish version of the Parkinson Disease Sleep Scale-2. Turkish Journal of Sleep Medicine. 2023;10(1):36-41.
17. 17. Temeloğlu Şen E, Sertel Berk Ö, Sindel D. The validity and reliability study of the Turkish adaptation of Medical Adherence Report Scale. Journal of Istanbul Faculty of Medicine. 2019;82(1):52-61.
18. 18. Muntean ML, Benes H, Sixel-Döring F, Chaudhuri KR, Suzuki K, Hirata K, et al. Clinically relevant cut-off values for the Parkinson’s Disease Sleep Scale-2 (PDSS-2): a validation study. Sleep Med. 2016;24:87-92.
19. 19. Vale TC, Santos DP, Oliveira DS, de Paula Brandão PR, Pereira DA, Bouça-Machado R, et al. Validation of the Portuguese version of the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) in Parkinson’s disease. Parkinsonism Relat Disord. 2025;132:107276.
20. 20. Cubo E, Luo S, Martínez-Martín P, Stebbins GT, Lin J, Choi D, et al. Expanded and independent Spanish validation of the MDS-Non Motor Rating Scale. Mov Disord Clin Pract. 2023;10(4):586-95.
21. 21. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1(8476):307-10.
22. 22. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989;45(1):255-68.
23. 23. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord. 2011;26(3):399-406.