Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study

Background: In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in beta-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependant beta-thalassemia major (TD-beta TM), using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy. Methods: Sixty-nine TD-beta TM patients (aged 1-16 years) and 15 healthy controls (aged 3-14 years) were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO), patients were divided into two groups: group [I] with chelation (n = 34) and group [II] without chelation (n = 35). Levels of creatinine (Cr), calcium (Ca), inorganic phosphorus (PO4), uric acid (UA) and albumin were measured by spectrophotometer. Serum (S) levels of cystatin-C (S-CysC) and total antioxidant capacity (S-TAC) and urinary (U) levels of beta(2)-microglobulin (U-beta 2MG) were measured by immunosorbent assay (ELISA). Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity and malondialdehyde (U-MDA) were measured by chemical methods. Estimated glomerular filtration rate (eGFR) was determined from serum creatinine. Results: In patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated S-UA, S-PO4, U-NAG/Cr, U-beta 2MG/Cr] and oxidative stress marker disturbances [diminished S-TAC and elevated U-MDA/Cr] were reported than controls. In patients with chelation, S-CysC was significantly higher while, S-TAC was significantly lower than those without chelation. In all patients, S-CysC showed significant positive correlation with S-Cr and negative correlation with eGFR; S-TAC showed significant positive correlation with eGFR and negative correlation with S-CysC, S-Cr, U-NAG/Cr; U-MDA/Cr showed significant positive correlation with U-albumin/Cr, U-beta 2MG/Cr, U-NAG/Cr. Conclusions: Our data confirm high frequency of glomerular and tubular dysfunctions in TD-beta TM pediatric patients which could be attributed to oxidative stress and DFO therapy.