Early Kidney Damage Markers after Deferasirox Treatment in Patients with Thalassemia Major: A Case-Control Study

Abstract

Background. The life of patients with β-thalassemia major depends on blood transfusion. Regular blood transfusion leads to hemosiderosis in their main organs. The aim of this study was to compare the effects of deferasirox and deferoxamine on renal damage in patients with β-thalassemia major. Method. The present case-control study was conducted on 60 individuals who were referred to the 17th Shahrivar Tertiary Referral Hospital in Guilan province, Iran. In this study, patients with β-thalassemia major who used deferasirox (n=21) and patients who used deferoxamine (n=19) were evaluated. The control group (n=20) was selected from healthy individuals. Serum creatinine (CREA), blood urea nitrogen (BUN), and Cystatin C were measured from blood samples. Furthermore, urinary (U.) neutrophil gelatinase-associated lipocalin (NGAL), albumin (Alb), interleukin- (IL-) 18, and Kidney Injury Molecule-1 (KIM-1) were measured by the ELISA method and normalized for U. creatinine (CREA). Results. U. NGAL, U. IL-18, and BUN biomarkers in the deferasirox group were significantly higher than those in the control group (p<0.001). U. NGAL/CREA and U. KIM-1/CREA ratios increased in both the deferoxamine and deferasirox groups compared to the control group (p<0.05). U. Alb was significantly higher in patients treated with deferoxamine than in healthy participants (p<0.05). Conclusion. The findings of this study indicate that after taking deferasirox, there was renal damage and an increase in inflammatory factors. Also, minor renal impairment was observed after deferoxamine administration, but it was not confirmed at the molecular level (U. NGAL and KIM-1). Therefore, it seems that patients who are taking these two drugs should be monitored carefully.

Comparison of Treatment Effects of Different Iron Chelators in Experimental Models of Sepsis

“…DFX has a weak metal-binding pyridinium group, which can hold iron in a redox-active state [ 21 ]. Consistent with this redox-reactive iron and our present findings, DFX has been reported to cause an increase in inflammatory factors and early renal damage in Thalassemic patients undergoing DFX therapy [ 22 ]. In contrast, DIBI holds iron in a redox-inactive state under physiological conditions [ 9 ].…”

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

“…Similar combinations of DFO and DFRA or L1 and DFRA, as well as other intensive chelation protocols have been tested. Unfortunately, as of now, neither improvements in safe iron removal, nor maintenance of iron at physiological levels have been reported yet, possibly due to iron-toxicity implications [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]. Overall, it appears that L1 is necessary for the achievement of the ultimate aim of iron chelation therapy, i.e., the achievement and maintenance of normal iron stores in regularly transfused and other categories of iron loaded patients [ 110 , 111 , 120 ].…”

Iron-withdrawing anti-infectives for new host-directed therapies based on iron dependence, the Achilles’ heel of antibiotic-resistant microbes

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