Renal tubular dysfunction in α-thalassemia

Abstract

Shortened red cell life span and excess iron cause functional and physiological abnormalities in various organ systems in thalassemia patients. In an earlier study, we showed that β-thalassemia patients have a high prevalence of renal tubular abnormalities. The severity correlated with the degree of anemia, being least severe in patients on hypertransfusion and iron chelation therapy, suggesting that the damage might be caused by the anemia and increased oxidation induced by excess iron deposits. This study was designed to define the renal abnormalities associated with α-thalassemia and to correlate the renal findings with clinical parameters. Thirty-four pediatric patients (mean age 8.2±2.8 years) with Hb H disease or Hb H/Hb CS were studied. Ten patients (group 1) were splenectomized, with a mean duration post splenectomy of 3.5±1.4 years; 24 patients (group 2) had intact spleens. The results were compared with 15 normal children. Significantly higher levels of urine N-acetyl-β-D-glycosaminidase, malondialdehyde (MDA), and β 2 -microglobulin were found in both groups compared with normal children. An elevated urine protein/creatinine ratio was recorded in 60% of group 1 and 29% of group 2. Two patients (5.9%), 1 in each group, had generalized aminoaciduria. We found proximal tubular abnormalities in α-thalassemia patients. Increased oxidative stress, possibly iron induced, may play an im-portant role, since urine MDA levels were significantly increased in both groups of patients.

Renal dysfunction in patients with thalassaemia

“…Several authors have reported abnormalities of renal tubular function in patients with thalassaemia major and intermedia, such as proteinuria, hypercalciuria, and hyperphosphaturia as well as increased urinary excretion of markers of tubular injury, such as N-acetyl-b-D-glycosaminidase, malondialdehyde, and b 2 -microglobulin. (Sumboonnanonda et al, 1998(Sumboonnanonda et al, , 2003Aldudak et al, 2000;Koliakos et al, 2003;Mohkam et al, 2008;Sadeghi-Bojd et al, 2008;Smolkin et al, 2008) Our findings of hypercalciuria, albuminuria, proteinuria, and excretion of b 2 -microglobulin are in accordance with prior reports of renal tubular dysfunction. However, these studies all reported normal GFR.…”

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

“…Also, we found in thalassemia patients, S TAC was significantly positively correlated with eGFR, negatively with S Cys , S Cr and U MDA /Cr was positive significant correlation with each of U NAG /Cr, U β2MG /Cr and U albumin /Cr. This emphasis the role of oxidative stress in inducing renal tubular damage [5,38,39]. Although severe anemia and chronic hypoxia are believed to play a role in renal involvement in βTM, lipid peroxidation is currently the most favored hypothesis: according to this hypothesis, the imbalance in synthesis of hemoglobin (Hb) leads to excess unpaired globin chain and high intracellular content of non-Hb iron.…”

“…The unstable Hb subunits are known to generate free oxygen radical species that starting a chain of oxidative events which leading to disintegration of denatured globin chains, heme, and iron, which bind to different membrane proteins and altering their normal structure and functions. In addition, the excess free iron is known to be a catalyst of lipid peroxidation via the fenton reaction [39]. …”

β-Thalassemia Intermedia: A Bird’s-Eye View

“…In thalassemic patients, the increased intracellular content of non-hemoglobin iron generates free oxygen radicals that bind to different membrane proteins, altering the morphology, function, and structure of membrane proteins [80]. Free iron can also directly catalyze lipid peroxidation by removing hydrogen atoms from the fatty acids that constitute the lipid bilayer of organelles [81].…”