RENAL-FUNCTION IN ADULT BETA-THALASSEMIA HB-E DISEASE

beta-Thalassemia hemoglobin E (beta-thal/Hb E) is the commonest form o f hemoglobinopathy in Thailand. Shortened red cell life span, rapid ir on turnover and tissue deposition of excess iron are major factors res ponsible for functional and physiological abnormalities found in vario us forms of thalassemia. Increased deposition of iron had been found i n 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 beta-thal/Hb E and provide evidence that i ncreased oxidative stress might be one of the factors responsible for the damage. Urine and serum samples from 95 patients with beta-thal/Hb E were studied comparing with 27 age-matched healthy controls. No dif ference in the creatinine clearance was observed, beta-thal/Hb E patie nts 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 patien ts. Analysis of urinary protein by SDS-PAGE electrophoresis and silver staining revealed abnormal pattern of protein with increased small mo lecular weight (<45 kD) bands. Morning urine analysis showed significa nt 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 beta(2)-microglobulin, 124.3 +/- 167 vs. 71 +/- 65.5 mu g/g Cr, p = 0 .001. Plasma and urine MDA (malonyldialdehyde) levels were both raised (p < 0.0001). Nine patients were selected for renal acidification stu dy, All were found to be normal, but showed poor response to DDAVP cha llenge (urine osmolality 533 +/- 71). This is the first report of rena l tubular defects found associated with beta-thal/Hb E disease. The me chanism 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.