Beta-thalassemia: renal complications and mechanisms: a narrative review

Abstract

Objectives: Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. Methods: A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. Results: Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. Discussion and Conclusion: Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

“…In line with our data, several other reports have shown that β-TM is associated with renal dysfunction [27][28][29]. Renal manifestations in β-TM have a multifactorial genesis related to the natural history of the disease: chronic anemia, potential associated chronic hypoxia, iron overload, and the use of specific iron chelators [27]. Şen et al [30] suggested that urinary NAG and NGAL may be considered reliable markers for monitoring renal injury in β-TM patients.…”

Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice

“…The observed adverse effect of excessive ERFE production on kidney function is potentially relevant for patients with β-thalassemia who suffer from renal complications. Kidney dysfunction in the context of β-thalassemia is incompletely understood but thought to result from a combination of iron-mediated damage, chronic anemia with renal hypoxia, and treatment with iron chelators that may damage the kidney (Demosthenous et al, 2019). Signaling by BMP7 is thought to protect against renal fibrosis (Zeisberg et al, 2003) and increased expression of BMP antagonists may predispose the kidney to tubular injury (Yanagita et al, 2006), exacerbating damage from excess iron or chelation therapy.…”

The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation

“…Up to 60% of patients with transfusion‐dependent thalassaemia (TDT) have been reported to develop signs of tubular dysfunction 37 . The prevalence of these conditions is bound to increase with advancing age as their presentation is related to both the course of the disease and the use of iron chelators 38,39 . Kidney disease may develop through progressive renal tubular and glomerular damage and renal disease is considered to be the fourth cause of morbidity among patients with TDT, accounting for 4% of deaths, after endocrine (44.7%), cardiovascular (41.3%) and hepatic (40.5%) disease 40 …”