Dapagliflozin in Patients with Homozygous β-Thalassemia and Albuminuria.

Abstract

Introduction: Patients with homozygous β-thalassemia show continuously improved survival, which has contributed to the development of kidney complications, predominantly expressed as increased albuminuria. In particular, patients with transfusion-dependent thalassemia frequently develop chronic kidney complications related to chronic anemia, iron overload, and exposure to iron chelation therapy. Although sodium-glucose co-transporter 2 inhibitors have demonstrated renoprotective effects in patients with chronic kidney disease (CKD) from other causes, their efficacy in patients with homozygous β-thalassemia and established CKD remains unknown.

Methods: In this prospective, open-label study, we investigated the impact of dapagliflozin (10 mg/day), in patients with homozygous β-thalassemia and an albumin-to-creatinine ratio (ACR) >30 mg/g. Study end-points included the effect on ACR and kidney function at 6 months after treatment initiation. Furthermore, we examined the effect on systolic blood pressure (SBP) and diastolic blood pressure, and on urine monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels.

Results: Twelve patients with ACR >30 mg/g received dapagliflozin, and 18 patients with normal ACR were followed up for 6 months. Twenty-three healthy adult individuals age- and sex-matched to the β-thalassemia group were used as normal controls. Patients with ACR >30 mg/g showed a significant reduction of ACR and SBP at 6 months (p = 0.034, p = 0.025, respectively), while kidney function remained stable. Patients with homozygous β-thalassemia showed increased baseline urine MCP-1 levels, while MMP-9 showed no differences versus normal controls. Those who received dapagliflozin exhibited a significant decrease in urine MCP-1 (p = 0.022), while MMP-9 remained stable. There were no significant adverse events.

Conclusion: Dapagliflozin at a standard dose of 10 mg daily is safe and effectively reduces albuminuria and urinary MCP-1 in patients with homozygous β-thalassemia and established CKD, suggesting potential kidney anti-inflammatory effects. Further studies with larger cohorts and longer follow-up are needed to determine its impact on CKD progression and long-term outcomes.