Iron Chelation Resulting in Renal Phosphate Wasting

Cheddani, Lynda; Leblanc, Thierry; Silve, Caroline; Tabibzadeh, Nahid; Prié, Dominique; Haymann, Jean‐Philippe; Péraldi, Marie-Noëlle; Daudon, Michel; Letavernier, Emmanuel

doi:10.1016/j.ekir.2017.07.011

Cited by 3 publications

(1 citation statement)

References 13 publications

(22 reference statements)

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“…Although α-Klotho regulates intestinal phosphate absorption, thereby maintaining circulating phosphate in the physiological range 81 , we could not detect hyperphosphatemia in TDT patients. This may be explained by the counterbalancing activities of iron chelators which increase renal phosphate excretion 82 . Future studies should investigate the effects of iron overload and accompanying inflammation and oxidative stress on PTH, calcyphosin, vitamin D3, phosphate, and FGFR2.…”

Section: Discussionmentioning

confidence: 99%

In Transfusion-dependent Thalassemia, Increased Iron Overload is Associated with Lower Serum Alpha-klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

Maes¹,

Moustafa²,

Al‐Hakeim³

et al. 2020

Preprint

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Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

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Section: Discussionmentioning

confidence: 99%

In Transfusion-dependent Thalassemia, Increased Iron Overload is Associated with Lower Serum Alpha-klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

Maes¹,

Moustafa²,

Al‐Hakeim³

et al. 2020

Preprint

View full text Add to dashboard Cite

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Chelating agents

2019

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In Transfusion-Dependent Thalassemia Children, Increased Iron Overload is Associated with Lower Serum Alpha-Klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

Moustafa

Al‐Hakeim

Alhillawi

et al. 2023

CMM

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Background: Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-Klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. The aim of the study is to examine the associations between low α-Klotho status and calcium metabolism in relation to iron status in children with TDT. Methods: Calcium, α-Klotho, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results: A meaningful part of TDT patients showed lowered α-Klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-Klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload and transfusions biomarkers (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-Klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion: In conclusion, the iron overload in TDT and its consequences may induce lowered levels of α-Klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

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Iron Chelation Resulting in Renal Phosphate Wasting

Cited by 3 publications

References 13 publications

In Transfusion-dependent Thalassemia, Increased Iron Overload is Associated with Lower Serum Alpha-klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

In Transfusion-dependent Thalassemia, Increased Iron Overload is Associated with Lower Serum Alpha-klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

Chelating agents

In Transfusion-Dependent Thalassemia Children, Increased Iron Overload is Associated with Lower Serum Alpha-Klotho, Which is Strongly Associated with Lower Total and Ionized Calcium Concentrations

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