Renal Function in Adult Beta-Thalassemia/Hb E Disease

Abstract

β-Thalassemia hemoglobin E (β-thal/Hb E) is the commonest form of hemoglobinopathy in Thailand. Shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are major factors responsible for functional and physiological abnormalities found in various forms of thalassemia. Increased deposition of iron had been found in renal parenchyma of thalassemic patients, but no systematic study of the effect of the deposits on renal functions has been available. The purpose of this study is to describe the functional abnormalities of the kidney in patients with β-thal/Hb E and provide evidence that increased oxidative stress might be one of the factors responsible for the damage. Urine and serum samples from 95 patients with β-thal/Hb E were studied comparing with 27 age-matched healthy controls. No difference in the creatinine clearance was observed. β-thal/Hb E patients excreted significantly more urinary protein (0.8 ± 0.5 vs. 0.3±0.1 g/day, p < 0.001). Aminoaciduria was found in 16% of the patients. Analysis of urinary protein by SDS-PAGE electrophoresis and silver staining revealed abnormal pattern of protein with increased small molecular weight (<45 kD) bands. Morning urine analysis showed significant lower urine osmolality (578.3 ± 164.6 vs. 762.4 ± 169.9 mosm/kg, p < 0.001) in patients. Patients excreted more NAG (N-acetyl beta-D-glucosaminidase, 26.3 ± 41.3 vs. 8.4 ± 3.9 U/g Cr, p < 0.0001) and β₂-microglobulin, 124.3 ± 167 vs. 71 ± 65.5 µg/g Cr, p = 0.001. Plasma and urine MDA (malonyldialdehyde) levels were both raised (p < 0.0001). Nine patients were selected for renal acidification study. All were found to be normal, but showed poor response to DDAVP challenge (urine osmolality 533 ± 71). This is the first report of renal tubular defects found associated with β-thal/Hb E disease. The mechanism leading to the damage is not known but it might be related to increased oxidative stress secondary to tissue deposition of iron, as indicated by the raised levels of serum and urine MDA. It is not known whether these functional defects would have any long-term effects on the patients. Further studies are warranted and means of prevention of these defects should urgently be sought.

Levels of Beta-2 Microglobulin and Cystatin C in Beta Thalassemia Major Patients

“…Creatinine and creatinine clearance did not statistically differ among the groups (p> 0.05). The results were similar to findings of both Sumboonnanonda et al, and Leena Ong-ajyooth et al [12,13]. Although the viewed glomerular filtration rates according to creatinine clearance in thalassemia group were detected within normal range in all patients, beta-2 microglobulin levels were significantly high in the control group (p <0.01).…”

“…Many reasons are proposed, although mechanism of kidney dysfunction in thalassemia is not exactly known [9,10]. Increased [11,12].…”

“…These defects were identified in the patients with splenectomy, which blood ferritin levels were also high. High serum levels of MDA showed role of oxidative stress in the pathogenesis [13]. In a study, Voskaridou et al [14] investigated glomerular dysfunction in patients with Beta Thalassemia Major measuring both glomerular and tubular filtration via new markers.…”

An infant with severe combined immunodeficiency syndrome, an α-thalassemia trait and renal Fanconi syndrome

“…8 An association between an immunodeficiency and Fanconi syndrome has not been reported, though there are a few reports of renal tubular defects associated with hemoglobinopathies. 9,10 The pathogenesis of tubular dysfunction described in patients with ␤-thalassemia/HbE disease 9,10 may also apply to other anemic states. In various forms of thalassemia shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are contributing factors to functional and physiological abnormalities.…”

“…In various forms of thalassemia shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are contributing factors to functional and physiological abnormalities. Ong-ajyooth et al 9 state that iron deposition in renal tubular cells may induce lipid peroxidation as shown by an excess of malondialdehyde in blood and urine. Sumboonnanonda et al 10 suggest that the renal damage in children with ␤-thalassemia is caused by anemia and increased oxidation induced by excess iron deposits.…”