Role of Cystatin C as Early Predictor of Renal Dysfunction in Iron Overloaded Beta Thalassemia Major Patients

Authors

  • Tamarra Haider Dheya Department of Community and Family Medicine, Faculty of Medicine, University of Babylon, Iraq
  • Ahmed Abdul-Mohsin Alshammary Department of Pediatrics, Faculty of Medicine, University of Babylon, Iraq
  • Ammar Hatem Abdullateef Department of Basic Sciences, College of Dentistry, University of Babylon, Iraq

DOI:

https://doi.org/10.48165/aabr.2026.3.1.03

Keywords:

cystatin c, Epidemiological and clinical factors, investigation, β-thalassemia

Abstract

Background: Beta thalassemia major patients are at risk to developing renal dysfunction over a period of time, secondary to chronic anemia, iron overload and chelation therapy. Early observation of renal insufficiency is necessary for intervention. Objectives: The objective of this study was to assess the value of cystatin c as an early marker of renal dysfunction in pediatric patients with iron overload Beta thalassemia major and investigates the related clinical factors. Patients and Methods: This was a cross sectional study which was conducted in Babylon center for hereditary blood disorders in Babylon governorate, 74 patients with beta thalassemia major whose parents accepted to participate in this study. Data collection was done by direct interview with parents. It was done by using performed questionnaire and tested for epidemiological and clinical factors. The concentration of cystatin C, creatinine, ferritin and haemoglobin were determined. Apparent correlations with cystatin C were analyzed for several factors, including age, age at presentation, duration of the disease, age at first blood transfusion and compliance with therapy and then take blood sample and examine the patient height. Results: A total of 74 patients with beta thalassemia major were enrolled in this study. Cystatin C adjusted concentrations showed a trend to increase with the later age at diagnosis (P < 0.0001); patients with diagnosis by 3-5 years were found the highest (1.42 ± 0.230 mg/L) compared to those diagnosed earlier at < 1 year (1.08 ± 0.248 mg/L) or between 1-3 years (1.11 ± 0.201 mg/L). Age at the first blood transfusion (P = 0.001) and therapy adherence (P = 0.032) were significantly associated with cystatin C levels and were higher in the non adherence group. Correlation of cystatin C was statistically in significant with serum creatinine (P = 0.047) while no correlation with age (P = 0.476) and duration of disease (P = 0.7) was observed unlike creatinine. There was significant correlation between cystatin C and serum ferritin.There was cut-off point of 1.34 mg/L serves as a critical warning sign, prompting further investigation and potentially earlier initiation of nephroprotective measures. Conclusion: Cystatin C proved to be a more sensitive biomarker than serum creatinine for the early detection of renal dysfunction in iron-overloaded β-thalassemia major patients. The study demonstrated that Cystatin C levels were significantly elevated in these patients, even before conventional markers such as serum creatinine showed abnormalities. This indicates that Cystatin C can play an essential role in the early prediction and monitoring of renal impairment, allowing for timely interventions to prevent progression, Additionally, demographic factors such as age and duration of blood transfusion therapy were found to influence renal function deterioration, highlighting the need for continuous monitoring in high-risk groups.

References

Al-Jefri, A. A., Alotaibi, N. K., & Alanazi, M. J. (2021). Role of serum cystatin C in detection of early renal impairment among beta-thalassemia major patients with iron overload. Saudi Journal of Kidney Diseases and Transplantation, 32(3), 550–557. https://pubmed.ncbi.nlm.nih.gov/33843816/

Al-Tameemi, R. H., & Altawry, A. K. (2020). Evaluation of cystatin C in early detection of renal dysfunction among β-thalassemia major patients. Journal of Pediatric Biochemistry, 10(1), 7–13. https://doi.org/10.4081/thal.2020.9007

Badeli, H., Sadeghi-Bojd, S., Ebrahimipour, M., & Ebrahimipour, H. (2019). Renal and cardiac complications in patients with beta-thalassemia major: A cross-sectional study. Caspian Journal of Internal Medicine, 10(1), 46–52. https://doi.org/10.5348/100051Z02AK2020AK

Behairy, L. G., El Mogy, I., Shaker, M., & Farid, S. (2017). Renal dysfunction in pediatric patients with beta-thalassemia major: Relation to chelation therapy. European Journal of Pediatrics, 176(5), 639–648. https://doi.org/10.1007/s00431-017-2898-3

Behairy, O. G., Abd Almonaem, E. R., Abed, N. T., et al. (2017). Role of serum cystatin-C and beta-2 microglobulin as early markers of renal dysfunction in children with beta-thalassemia major. International Journal of Nephrology and Renovascular Disease, 10, 261–268. https://doi.org/10.2147/IJNRD.S142824

Bilir, O., Yurekli, B. S., Gursel, T., et al. (2021). Renal involvement in transfusion-dependent β-thalassemia: Elevated cystatin C and proteinuria associated with iron overload. BMC Nephrology, 22(1), Article 418. https://doi.org/10.1186/s12882-021-02630-5

Demosthenous, C., Vlachaki, E., Apostolou, C., et al. (2019). Beta-thalassemia: Renal complications and mechanisms—A narrative review. Hematology, 24(1), 426–438. https://doi.org/10.1080/16078454.2019.1599096

Fairweather-Tait, S. J., Wawer, A. A., Gillings, R., Jennings, A., & Myint, P. K. (2014). Iron status in the elderly. Mechanisms of Ageing and Development, 136–137, 22–28. https://doi.org/10.1016/j.mad.2013.11.005

Grubb, A., Horio, M., Hansson, L. O., Björk, J., Nyman, U., Flodin, M., Larsson, A., & Shimizu, A. (2015). Generation of a new cystatin C-based estimating equation for glomerular filtration rate. Clinical Chemistry, 61(4), 947–956. https://doi.org/10.1373/clinchem.2014.225102

Hamdy, A. M., Abdel-Latif, H. M. R., & El-Din, A. N. (2021). Assessment of early kidney dysfunction in children with beta-thalassemia major using serum cystatin C and urinary biomarkers. Journal of Pediatric Nephrology, 9(2), 45–52.

Hamdy, M., Shaheen, I., El-Gammal, Z. M., El-Sisi, A., & El-Shabrawi, M. (2021). Detection of renal insufficiency in patients with beta-thalassemia major using cystatin-C. Journal of Pediatric Hematology/Oncology, 43(8), e1010–e1014. https://doi.org/10.1097/MPH.0000000000002171

Hamdy, N. A., El-Haddad, A. A., Abdel-Ghaffar, N. S., & El-Masry, S. M. (2017). Serum cystatin C as an early marker of renal dysfunction in children with beta-thalassemia major. Journal of Pediatric Hematology/Oncology, 39(3), 174–178.

Hemieh, M., Khosravi, M., & Seighali, F. (2017). Iron overload and oxidative stress in beta-thalassemia major patients. Iranian Journal of Pediatric Hematology and Oncology, 7(4), 236–241.

Inker, L. A., Schmid, C. H., Tighiouart, H., Eckfeldt, J. H., Feldman, H. I., Greene, T., & Levey, A. S. (2012). Estimating glomerular filtration rate from serum creatinine and cystatin C. New England Journal of Medicine, 367(1), 20–29. https://doi.org/10.1056/NEJMoa1114248

Levey, A. S., Inker, L. A., & Coresh, J. (2020). GFR estimation: From physiology to public health. American Journal of Kidney Diseases, 75(6), 919–929. https://doi.org/10.1053/j.ajkd.2019.12.001

Mahmoud, A. A., Abd Elaziz, D. S., & Ahmed, R. H. (2021). Evaluation of renal tubular dysfunction in children with β-thalassemia major. The Egyptian Journal of Haematology, 46(2), 134–139.

Mahmoud, A. A., Elian, D. M., & Abd El Naby, S. A. (2021). Serum cystatin-C as a predictive marker in evaluation of glomerular dysfunction in beta-thalassemia major patients. Journal of Blood Medicine, 12, 1–10. https://doi.org/10.2147/JBM.S287921

Mahmoud, A. A., Elian, D. M., Abd El Hady, N. M., et al. (2021). Assessment of subclinical renal dysfunction in children with beta-thalassemia major. Children, 8(2), 100. https://doi.org/10.3390/children8020100

Mahmoud, M. H., Soliman, A., Alaarag, A., Elghoneimy, Y., & Ragab, I. A. (2021). Early detection of renal dysfunction in children with beta-thalassemia major. Hematology, 26(1), 568–574.

Makmettakul, S., Rattanathanya, W., Rattanachai, S., et al. (2020). Cardiorenal syndrome in thalassemia patients. BMC Nephrology, 21, Article 17. https://doi.org/10.1186/s12882-020-01990-8

Modell, B., & Darlison, M. (2008). Global epidemiology of haemoglobin disorders. Bulletin of the World Health Organization, 86(6), 480–487. https://doi.org/10.2471/BLT.06.036673

Musallam, K. M., Cappellini, M. D., & Taher, A. T. (2016). Iron overload in β-thalassemia intermedia. Current Opinion in Hematology, 23(3), 218–225. https://doi.org/10.1097/MOH.0000000000000234

Musallam, K. M., Sankaran, V. G., Cappellini, M. D., et al. (2021). Clinical epidemiology of β-thalassemia. Blood Reviews, 50, 100837. https://doi.org/10.1016/j.blre.2021.100837

Musallam, K. M., Cappellini, M. D., & Taher, A. T. (2021). Iron overload in beta-thalassemia intermedia. Current Opinion in Hematology, 28(3), 184–190.

Musallam, K. M., Cappellini, M. D., Taher, A. T., & Rachmilewitz, E. A. (2016). Iron overload and renal dysfunction in beta-thalassemia major. American Journal of Hematology, 91(1), 113–120. https://doi.org/10.1002/ajh.24209

Musallam, K. M., Rivella, S., Vichinsky, E., & Rachmilewitz, E. A. (2013). Non-transfusion-dependent thalassemias. Haematologica, 98(6), 833–844. https://doi.org/10.3324/haematol.2012.066845

Origa, R. (2017). Beta-thalassemia. Genetics in Medicine, 19(6), 609–619. https://doi.org/10.1038/gim.2016.173

Porter, J. B., & Garbowski, M. W. (2019). Pathophysiology of transfusional iron overload. Hematology/Oncology Clinics of North America, 33(3), 339–352. https://doi.org/10.1016/j.hoc.2019.01.002

Romadhon, A. F., Rachmadi, D., Rahardjo, T. H., & Putri, D. A. (2022). Renal involvement in beta-thalassemia major patients. International Journal of Nephrology, 2022, 7124925. https://doi.org/10.1155/2022/7124925

Romadhon, A., Widodo, I., & Kartasasmita, R. E. (2022). Markers of renal complications in beta-thalassemia patients. Journal of Blood Medicine, 13, 1–10. https://doi.org/10.2147/JBM.S387416

Saghir, S., Riaz, A., Hasan, A., Bhatti, Y. A., Iqbal, M., & Afzal, M. (2020). Cystatin C as an early marker of glomerular dysfunction. The Professional Medical Journal, 27(2), 1–5. https://doi.org/10.29309/TPMJ/2020.27.02.3566

Shlipak, M. G., Matsushita, K., Ärnlöv, J., et al. (2013). Cystatin C versus creatinine in kidney function. New England Journal of Medicine, 369(10), 932–943. https://doi.org/10.1056/NEJMoa1214234

Shwayel, A. J., Jewad, A. M., & Abdulsattar, M. Q. (2023). Evaluation of serum cystatin-C and netrin-1. Journal of Applied Hematology, 14(3), 236–241. https://doi.org/10.4103/joah.joah_29_23

Taher, A. T., Weatherall, D. J., & Cappellini, M. D. (2018). Thalassaemia. The Lancet, 391(10116), 155–167. https://doi.org/10.1016/S0140-6736(17)31822-6

Taher, A. T., Musallam, K. M., & Cappellini, M. D. (2018). β-Thalassemias. New England Journal of Medicine, 378(4), 370–371. https://doi.org/10.1056/NEJMc1716152

Taher, A. T., Weatherall, D. J., & Cappellini, M. D. (2021). Thalassaemia. The Lancet, 397(10291), 373–386. https://doi.org/10.1016/S0140-6736(20)32172-5

Tanous, O., Azulay, Y., Halevy, R., et al. (2021). Renal function in β-thalassemia major patients. BMC Nephrology, 22, 418. https://doi.org/10.1186/s12882-021-02630-5

Published

2026-04-03

How to Cite

Role of Cystatin C as Early Predictor of Renal Dysfunction in Iron Overloaded Beta Thalassemia Major Patients . (2026). Advances in Applied Biological Research, 3(1), 29-39. https://doi.org/10.48165/aabr.2026.3.1.03