The Effect of Iron Chelators on urine Beta Microglobulin(β2M) and Serum Sodium on Patients with Thalassemia Major

Background and Objectives Thalassemia is the most common genetic disease associated with the body's recurrent blood transfusions and iron overload. Iron chelators can reduce the adverse effects of iron overload through various mechanisms. However, concerns have recently been raised about their negative impact on renal function. The current study, therefore, examined the effect of different iron chelators on renal function in patients with thalassemia major. Subjects and Methods This cross-sectional descriptive study included primary thalassemia patients (5 - 25 years) referring to Ahwaz Thalassemia Center for regular blood transfusion and regular treatment with iron chelators. They were divided into 3 groups (deferiprone 60-80 mg/kg/d, deferasirox 15-35 mg/kg/d and deferoxamine 11-48 mg/kg/d). Blood and 24-hour urine samples were collected to determine glomerular filtration rate (GFR) and biochemical factors. Results No significant difference was observed between the studied groups in terms of GFR, urine albumin, serum creatinine, serum cystatin C, serum and urine phosphorus, and urine sodium (p > 0.05), but serum sodium and urine β2microglobulin (β2M) were significantly different between the studied groups (p < 0.05). Serum sodium was significantly higher in the deferiprone group compared to the control (P=0.004). Urine β2M was significantly higher in the deferoxamine and deferasirox groups in comparison with the control group (P=0.041, P=0.013). Finally, serum sodium was significantly higher in the deferiprone and deferasirox groups than that in the deferoxamine group (P=0.001, P=0.021). Conclusion Urine beta-2 microglobulin increased in patients receiving deferoxamine and deferasirox compared to the control group, which might indicate primary kidney damage.


Extended Abstract
Introduction halassemia is the most common genetic disease associated with the body's recurrent blood transfusions and iron overload.Iron chelators are compounds designed to bind and remove excess iron from the body.By leveraging various mechanisms, they work to counteract the harmful impact of iron overload, which is often a consequence of recurrent blood transfusions in individuals with thalassemia.Iron chelators can reduce the adverse effects of iron overload through various mechanisms.However, concerns have recently been raised about their negative impact on renal function.Hence, the current study examined the effect of different iron chelators on renal function in patients with thalassemia major.Findings of this study could greatly inform medical decisions and treatment strategies, contributing to optimization of the care and well-being of individuals grappling with thalassemia and iron overload.

Methods
This cross-sectional descriptive study included primary thalassemia patients aged 5 to 25 years.These individuals received regular blood transfusions as well as consistent treatment with iron chelators.They were divided into three distinct groups based on the specific iron chelator they were using.The groups were as follows: 1. Deferiprone Group: Individuals in this group received a dosage of 60-80 mg/kg/day of deferiprone.

Deferasirox Group:
Patients in this group underwent treatment with a dosage ranging from 15-35 mg/kg/day of deferasirox.

Deferoxamine Group:
This group consisted of individuals who received treatments with dosages varying from 11-48 mg/kg/day of deferoxamine.
Data collection included both blood and 24-hour urine samples obtained from the individuals in these groups.These samples were then used to determine the glomerular filtration rate (GFR) as well as various biochemical factors.The GFR is a specific measure used to assess how well the kidneys are filtering waste from the blood, thus providing valuable insights into kidney function.The principal goal of this research was to understand and compare the impact of these different iron chelators, deferiprone, deferasirox, and deferoxamine, on the glomerular filtration rate and the relevant biochemical factors in primary thalassemia patients within the specified age range.
By studying the effects of these different iron chelators on kidney function and the relevant biochemical markers, the researchers aimed to provide valuable data that could contribute to informed decision-making in thalassemia patient care.Findings of this study has the potential to help optimize treatment strategies, minimize potential risks, and improve the overall health and well-being of individuals with thalassemia and its associated treatments.

Results
No significant differences were observed between the studied groups in terms of GFR, urine albumin, serum creatinine, serum cystatin C, serum and urine phosphorus, and urine sodium (p-value> 0.05).However, our analysis did reveal a few significant differences among the groups: -Serum Sodium: The serum sodium levels were notably different among the groups.Specifically, the deferiprone group exhibited significantly higher serum sodium levels compared to the control group (p=0.004).Additionally, serum sodium was significantly higher in the deferiprone and deferasirox groups compared to the deferoxamine group (p=0.001,p=0.021).
-Urine β2microglobulin (β2M): The levels of urine β2Microglobulin were significantly higher in the deferoxamine and deferasirox groups compared to the control group (p=0.041,p=0.013).These findings suggest that while several biochemical factors and GFR did not show any substantial differences among the studied groups, there were significant variations in serum sodium levels and urine β2Microglobulin levels.This indicates that different iron chelators may have distinct impacts on these specific markers.Understanding these distinctions can be crucial for healthcare professionals managing thalassemia patients, as it sheds light on the potential various effects of different iron chelators on these particular biochemical factors.Findings of this study can contribute to tailored and more precise treatment approaches for individuals with thalassemia.More specifically, they provide valuable insights into the potential effect of different iron chelators on specific biochemical markers, contributing to a deeper understanding of the nuanced effects of these treatments on kidney function and the related factors in thalassemia patients.

Conclusion
The observation that urine beta-2 microglobulin (β2M) levels increased in patients receiving deferoxamine and deferasirox compared to the control group suggests a potential indication of primary kidney damage.Understanding Urine Beta-2 Microglobulin (β2M): Beta-2 microglobulin is a protein found on the surface of many cells, including those in the kidneys.When kidneys are functioning normally, only trace amounts of this protein are found in the urine.However, increased levels of β2M in urine can be a sign of kidney damage because it indicates that the kidneys may not be effectively filtering and retaining this protein as they should.In the context of this study, the elevated levels of urine β2Microglobulin in patients receiving deferoxamine and deferasirox compared to the control group suggest the possibility of primary kidney damage.This increase may indicate that these specific iron T chelators, deferoxamine and deferasirox, could potentially contribute to or be associated with kidney damage in thalassemia patients.These findings have important clinical implications.Specifically, they warrant close monitoring and assessment of kidney function in individuals with thalassemia who receive these specific iron chelators.Monitoring urine β2Microglobulin levels can offer insight into the potential impact of these treatments on kidney health and guide healthcare professionals in adjusting treatment plans and implementing appropriate interventions to safeguard kidney function.This observation may prompt further research and exploration into the precise effects of these iron chelators on kidney function and β2M levels.Understanding the mechanisms behind the increase in urine β2Microglobulin levels can potentially lead to the development of strategies to mitigate any potential kidney damage associated with these treatments while optimizing their benefits in managing iron overload in thalassemia patients.In summary, the increase in urine β2Microglobulin levels in patients receiving deferoxamine and deferasirox compared to the control group suggests a potential indicator of primary kidney damage.This underscores the importance of ongoing vigilance and assessment of kidney health in individuals with thalassemia undergoing treatment with iron chelators.