Glomerulotubular function in transfusion-dependent thalassemia children: a prospective cohort study

Abstract

Introduction: Thalassemia is the most common hemoglobinopathy in Indonesia. Chronic anemia, iron overload, and treatment with iron chelating agents are factors that contribute to kidney dysfunction in children with transfusion-dependent thalassemia (TDT). Urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine albumin-creatinine ratio (uACR) are markers of glomerular and tubular damage. Objectives: To analyze the glomerulotubular function in TDT children. Patients and Methods: This prospective cohort study recruited 40 TDT children aged ≤18 years old from thalassemia transfusion outpatient clinic, Dr. Cipto Mangunkusumo general hospital, Jakarta, Indonesia between February and June 2021. Disease history, treatment, and anthropometry were obtained during enrollment (T0). Blood and urine samples were taken at enrollment (T0) and at 1 (T1), 2 (T2), and 3 (T3) month follow-up appointments. Data analyzed were iron chelating agent, ferritin, hemoglobin, estimated glomerular filtration rate (eGFR ), uNGAL, uACR levels. Results: We observed kidney hyperfiltration in more than 30% of the participants. Transfusion volume was the most dominant factor for eGFR (β=-0.974, P=0.022) and uNGAL (β=0.872, P=0.015). A low-proportion of albuminuria was found with duration of disease as the predominant factor (β=-0.946, P=0.000). Deferiprone (DFP) and deferasirox (DFX) showed comparable association with all kidney biomarkers. Conclusion: The findings of this study indicate glomerular hyperfiltration in TDT children as the main early sign of glomerulotubular function impairment. In addition, a small proportion of proteinuria was also found in our study. Thus, both biomarkers should be part of long term kidney follow up in TDT children.