Iron overload and urinary lysosomal enzyme levels in β-thalassaemia major

Abstract

Iron overload resulted in increased urinary levels of the lysosomal enzyme NAG which has been proposed as an early marker of kidney damage. Reduction of iron load, achieved by regular desferrioxamine infusion, resulted in normalisation of the urinary enzyme levels. Thus kidney lysosomes appear to be a target and possibly a mediator of iron toxicity in this tissue.

Mechanisms of Renal Disease in β-Thalassemia

“…[8][9][10] The mechanism of injury is mediated by mitochondrial stress in proximal tubular cells, as evidenced by increased efflux of cytochrome C, release of lactate dehydrogenase, and reduction in adenosine triphosphate. 11,12 This pathologic and experimental evidence is supported by clinical studies showing a good correlation between serum ferritin levels and markers of tubular toxicity, 13,14 and by reversal of tubular defects after iron chelation therapy. 14,15 Chronic anemia and hypoxia are also associated with oxidative stress, lipid peroxidation, and functional abnormalities in tubular cells.…”

“…11,12 This pathologic and experimental evidence is supported by clinical studies showing a good correlation between serum ferritin levels and markers of tubular toxicity, 13,14 and by reversal of tubular defects after iron chelation therapy. 14,15 Chronic anemia and hypoxia are also associated with oxidative stress, lipid peroxidation, and functional abnormalities in tubular cells. 16,17 Damage to the proximal tubule and volume increases of the peritubular space were also demonstrated in one study on anemic rats.…”

GFR in Patients with β-Thalassemia Major

“…Similarly, iron overload in rats led to mild proteinuria with iron deposits in glomeruli, proximal tubules, and interstitium associated with glomerulosclerosis, tubular atrophy, and interstitial fibrosis (38). Several studies reported correlation between serum ferritin levels and markers of tubular toxicity, which iron chelation therapy reversed (7,39). Other studies have shown renal tubular abnormalities related to duration of chelation, duration of transfusions, amount of transfusions, and body iron content, as measured by magnetic resonance imaging (5,7,8).…”

Perbandingan Kadar N-Acetyl-ß-D-Glucosaminidase Urin pada Thalassemia ß Mayor Anak yang Mendapat Deferipron dan Deferasiroks

“…4 Kelebihan besi dan anemia kronik merupakan faktor utama penyebab abnormalitas tubulus ginjal. 1,3,5,6 Pada kasus TßM, beberapa penelitian tentang disfungsi ginjal memperlihatkan bahwa pemeriksaan biokimia rutin tidak dapat mendeteksi dini kerusakan tubulus ginjal. 7,8 Penelitian lain membuktikan bahwa N-acetyl-β-D-glucosaminidase (NAG) merupakan pemeriksaan yang paling dapat diandalkan untuk mendeteksi dini kerusakan tubulus ginjal pada TßM dibandingkan dengan pemeriksaan yang lain.…”

“…7,8 Penelitian lain membuktikan bahwa N-acetyl-β-D-glucosaminidase (NAG) merupakan pemeriksaan yang paling dapat diandalkan untuk mendeteksi dini kerusakan tubulus ginjal pada TßM dibandingkan dengan pemeriksaan yang lain. 2,9,5,10,11 Luasnya pemakaian kelasi besi per oral, terma s uk di Indonesia, menuntut banyak peneliti melaku kan penelitian mengenai manfaatnya dalam mengura ngi kelebihan besi dalam tubuh, tetapi disisi lain juga dituntut untuk melakukan penelitian mengenai efektivitasnya dalam mempertahankan fungsi organ termasuk ginjal. Sampai saat ini, penelitian mengenai hubungan penggunaan kelasi besi oral dengan fungsi tubulus ginjal belum ditemukan.…”