Netrin-1 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in ß-thalassemia major children.

BACKGROUND: Children with ß-thalassemia major (ß-TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention. AIM: This study aims to preliminary assess Netrin-1(NTN-1) and clusterin (CLU) in ß-TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction. SUBJECTS AND METHODS: In this study, 40 ß-TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN-1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real-time PCR. Serum TNF-α, MDA levels and GST activity were measured. RESULTS: Urinary NTN-1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in ß-TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in ß-TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN-1 and CLU levels are of promising diagnostic performance. CONCLUSION: Our results suggest that NTN-1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in ß-TM children. Moreover, urinary NTN-1 is recommended as a precise one during the clinical practices.

Therapeutic mechanism of combined oral chelation therapy to maximize efficacy of iron removal in transfusion-dependent thalassemia major - a pilot study.

OBJECTIVES: Three iron chelators are used to treat transfusion-dependent beta-thalassemia: desferrioxamine (DFO), deferasirox (DFX), and deferiprone (DFP). Compliance is low for DFO as it cannot be administered orally. Combined administration of DFP and DFX is orally available, however, the therapeutic mechanism is unknown. This pilot study investigated the iron removal mechanisms of DFX and DFP treatment in patients with transfusion-dependent thalassemia major. METHODS: Each patient received three treatments sequentially: (1) DFX monotherapy, (2) DFP monotherapy, and (3) DFX/DFP combination therapy with a four-day washout period between each treatment. Urine and stool specimens were collected to determine the primary outcome of iron excretion volumes. RESULTS: The mean iron excretion was seven times higher after combination therapy with DFX and DFP. Monotherapies also increased excretions volumes, though to a significantly lesser degree. Combined administration of DFX and DFP achieves maximum iron removal in transfusion-dependent thalassemia major compared to monotherapy with either drug. CONCLUSIONS: We suggest combination therapy in chronic severe iron overload cases, especially for patients in poor compliance with DFO/DFP combination therapy or those exhibiting poor iron removal from DFX or DFP monotherapy.

Evaluation of Proteinuria in ß-Thalassemia Major Patients With and Without Diabetes Mellitus Taking Deferasirox.

BACKGROUND: ß-thalassemia is the most common heredity disease in Iran. Regular blood transfusion is critical to sustain life and normal growth. Deferasirox is an oral chelator. One of the side effects of the deferasirox is proteinuria. OBJECTIVES: This study aimed to investigate the safety of deferasirox on kidney function in diabetic and nondiabetic ß-thalassemia major patients. MATERIALS AND METHODS: In this cross-sectional study, 34 diabetic and 36 nondiabetic patients who take deferasirox (Exjade) 20 to 40 mg/kg/d were studied. Exclusion criteria included patient with renal failure, proteinuria, hepatitis B, hepatitis C, and the patients who refused to continue the study to the end. Subjects were divided into diabetic and nondiabetic groups. Spot urine protein/creatinine ratio, urinary analysis, alanine transaminase, aspartate transaminase, creatinine, fasting blood sugar, blood urea nitrogen, and serum ferritin were checked every 3 months. Patients were followed for a period of 1 year. RESULTS: In the ninth month after therapy there was a significant relationship in mean change of spot urine protein/creatinine ratio between diabetic and nondiabetic (P=0.011). Spot urine protein/creatinine ratio in diabetic and nondiabetic group was 0.19±0.18 and 0.1±0.05, respectively, which showed no significant relationship between the 2 groups at the end of study (P=0.162). CONCLUSION: The results of our study showed that consumption of deferasirox is safe, as there was no significant relationship between spot urine protein/creatinine ratio in diabetic and nondiabetic group. Deferasirox consumption is not associated with increased proteinuria in diabetic patients compared with nondiabetic group having only a transient proteinuria.

A prospective study of tubular dysfunction in pediatric patients with Beta thalassemia major receiving deferasirox.

BACKGROUND: Beta thalassemia major is a lifelong transfusion-dependent disorder. Transfusion-dependent thalassemia patients are prone to develop renal dysfunction due to iron overload, chronic anemia, and/or chelation therapy. METHODS: In this prospective study, thalassemia patients who fitted inclusion and exclusion criteria received Deferasirox 20 mg/kg/day. A complete biochemistry analysis of serum and 24-hour-urine specimens was performed before and after treatment. Estimated glomerular filtration rate (eGFR), Fractional excretion of sodium (FENA), potassium (FEK), uric acid (FEUA), and the maximum ratio of tubular reabsorption of phosphorus to eGFR (TmP/GFR) at baseline and after treatment was calculated and compared. RESULTS: A total of 30 patients with mean age of 4.9 ± 3.2 years were recruited. The mean serum creatinine increased significantly after 6 months of treatment (0.54 ± 0.08 vs. 0.67 ± 0.16, P < .001) while eGFR was decreased (104.36 ± 19.62 vs. 86.00 ± 16.92, P < .001). Mean potassium level in serum was increased after treatment, while serum calcium, magnesium, and uric acid levels decreased significantly (P > .05). A significant increase was confirmed for mean urinary ß2-microglobulin (ß2-MG), protein, uric acid, calcium, and magnesium (P > .05). CONCLUSION: Our findings highlighted tubular nephropathy induced by Deferasirox in patients with beta thalassemia, and confirmed the necessity for diligent monitoring of renal function in thalassemia patients receiving Deferasirox.

Comparison of pharmacokinetics and urinary iron excretion of two single doses of deferiprone in ß-thalassemia/hemoglobin E patients.

Dose-related pharmacokinetics and urinary iron excretion (UIE) of an orally active iron chelator, deferiprone (L1), was investigated in 12 severe ß-thalassemia/hemoglobin E patients. The patients received two single doses of 25 and 50 mg/kg with a 2-week washout period. Deferiprone was rapidly absorbed and reached maximum concentration (C(max)) within 1 h after administration. Pharmacokinetic parameters including C(max) and area under concentration time curve from time zero to infinity (AUC(0-∞)) as well as urinary excretion of non-conjugated and glucuronide-conjugated deferiprone (L1 and L1-G) increased proportionally with the dose of deferiprone. A constant ratio of AUC(0-∞) of L1-G to L1 and a percentage of urinary excretion of L1-G indicated that increasing the dosage does not influence deferiprone biotransformation. Longer terminal elimination half-lifeand higher volume of distribution of L1 were observed with the high dose and correlated with deferiprone-chelated iron in serum. Unexpectedly, UIE did not show a linear relationship with the increased dose of deferiprone. The correlation between UIE and creatinine clearance suggested the possibility of L1-iron complex redistribution in patients with renal impairment treated with high-dose deferiprone.

Hepcidin expression in iron overload diseases is variably modulated by circulating factors.

Hepcidin is a regulatory hormone that plays a major role in controlling body iron homeostasis. Circulating factors (holotransferrin, cytokines, erythroid regulators) might variably contribute to hepcidin modulation in different pathological conditions. There are few studies analysing the relationship between hepcidin transcript and related protein expression profiles in humans. Our aims were: a. to measure hepcidin expression at either hepatic, serum and urinary level in three paradigmatic iron overload conditions (hemochromatosis, thalassemia and dysmetabolic iron overload syndrome) and in controls; b. to measure mRNA hepcidin expression in two different hepatic cell lines (HepG2 and Huh-7) exposed to patients and controls sera to assess whether circulating factors could influence hepcidin transcription in different pathological conditions. Our findings suggest that hepcidin assays reflect hepatic hepcidin production, but also indicate that correlation is not ideal, likely due to methodological limits and to several post-trascriptional events. In vitro study showed that THAL sera down-regulated, HFE-HH and C-NAFLD sera up-regulated hepcidin synthesis. HAMP mRNA expression in Huh-7 cells exposed to sera form C-Donors, HFE-HH and THAL reproduced, at lower level, the results observed in HepG2, suggesting the important but not critical role of HFE in hepcidin regulation.

Timed non-transferrin bound iron determinations probe the origin of chelatable iron pools during deferiprone regimens and predict chelation response.

BACKGROUND: Plasma non-transferrin bound iron refers to heterogeneous plasma iron species, not bound to transferrin, which appear in conditions of iron overload and ineffective erythropoiesis. The clinical utility of non-transferrin bound iron in predicting complications from iron overload, or response to chelation therapy remains unproven. We undertook carefully timed measurements of non-transferrin bound iron to explore the origin of chelatable iron and to predict clinical response to deferiprone. DESIGN AND METHODS: Non-transferrin bound iron levels were determined at baseline and after 1 week of chelation in 32 patients with thalassemia major receiving deferiprone alone, desferrioxamine alone, or a combination of the two chelators. Samples were taken at baseline, following a 2-week washout without chelation, and after 1 week of chelation, this last sample being taken 10 hours after the previous evening dose of deferiprone and, in those receiving desferrioxamine, 24 hours after cessation of the overnight subcutaneous infusion. Absolute or relative non-transferrin bound iron levels were related to transfusional iron loading rates, liver iron concentration, 24-hour urine iron and response to chelation therapy over the subsequent year. RESULTS: Changes in non-transferrin bound iron at week 1 were correlated positively with baseline liver iron, and inversely with transfusional iron loading rates, with deferiprone-containing regimens but not with desferrioxamine monotherapy. Changes in week 1 non-transferrin bound iron were also directly proportional to the plasma concentration of deferiprone-iron complexes and correlated significantly with urine iron excretion and with changes in liver iron concentration over the next 12 months. CONCLUSIONS: The widely used assay chosen for this study detects both endogenous non-transferrin bound iron and the iron complexes of deferiprone. The week 1 increments reflect chelatable iron derived both from liver stores and from red cell catabolism. These increments correlate with urinary iron excretion and the change in liver iron concentration over the subsequent year thus predicting response to deferiprone-containing chelation regimes. This clinical study was registered at clinical.trials.gov with the number NCT00350662.

Fok-I polymorphism of vitamin D receptor gene and the presence of renal dysfunction in patients with ß-thalassemia major.

Recent evidence supports the presence of renal dysfunction even among young patients with ß-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with ß-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5-22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary ß(2)-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.

Renal dysfunction in patients with beta-thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or with deferasirox.

There are limited studies on renal involvement in beta-thalassemia, mainly involving patients on deferoxamine, reporting both glomerular and tubular dysfunction. The aim of the present study was to investigate renal involvement in young thalassemia patients, using both conventional and early markers of renal dysfunction, and to correlate findings to iron chelation therapy. Forty-two patients aged 4-23 years were studied and, for analysis purposes, were divided into two groups based on chelation therapy (group A receiving deferasirox and group B receiving deferoxamine and deferiprone combination therapy). In addition to conventional renal biochemistries, creatinine clearance, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium, tubular phosphorus reabsorption and urine calcium, protein, beta(2)-microglobulin (beta(2)-MG) and glucose levels were measured. A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (36%), glomerular dysfunction with proteinuria (24%) and tubulopathy with hypercalciuria (35.5%) and elevated excretion of beta(2)-MG (33.5%). Renal involvement seems to be present even in young patients with beta-thalassemia, therefore, routine use of early markers of renal dysfunction is recommended. Further studies are needed in order to investigate the role of new chelators in tubular function parameters.

Urinary cysteinyl leukotriene E4 significantly increases during pain in children and adults with sickle cell disease.

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.

Phase Ib clinical trial of starch-conjugated deferoxamine (40SD02): a novel long-acting iron chelator.

The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.

The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis.

Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM-patients, suggesting their involvement in the pathogenesis of beta TM-osteoporosis.

Urinary hepcidin in congenital chronic anemias.

BACKGROUND: Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias. PROCEDURE: Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion. RESULTS: In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P = 0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count. CONCLUSIONS: This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production.

Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle.

UNLABELLED: Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis. INTRODUCTION: Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. MATERIALS AND METHODS: We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin. RESULTS: Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio. CONCLUSIONS: Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients.

Urinary iron excretion induced by intravenous infusion of deferoxamine in beta-thalassemia homozygous patients.

The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent beta-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 beta-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF). Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally, the use of 3-9 g intravenous DF for 6-12 days led to a urinary iron excretion corresponding to 4.1 to 22.4% of the annual transfusion iron gain. Therefore, continuous intravenous DF at high doses may be an additional treatment for these patients, as a complement to the regular subcutaneous infusion at home, but requires individual planning and close monitoring of adverse reactions.

Safety profile of the oral iron chelator deferiprone: a multicentre study.

In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.

Pattern of iron excretion in relation to haemoglobin level and iron load in 8 haematological patients following the administration of subcutaneous deferrioxamine.

Iron excretion following subcutaneous administration of deferrioxamine (DFO) was measured between two transfusions of packed red cells in 6 patients with beta-thalassaemia major on the high level Hb transfusion regime; and in a single 3-day period in 2 other patients, 1 with transfused beta-thalassaemia major and the other with haemolytic anaemia due to PK deficiency. The pattern of iron excretion did not change significantly during the period between the two transfusions and was found to be related to serum ferritin levels. The proportion of iron excreted in the stools was inversely related to the serum ferritin level. These observations on iron excretion are of practical importance in relation to DFO administration, especially when evaluated in thalassaemics with normal haemoglobin levels and low iron stores.

Desferrioxamine and urinary zinc excretion in beta-thalassemia major.

This study has been undertaken to find out whether urinary zinc excretion, which is already increased in patients with thalassemia, is further increased by usual and high doses of desferrioxamine (DF). A total of 11 beta-thalassemia major patients were included. DF infusions have been performed with doses, either 50 mg/kg or 150 mg/kg. Nine age and sex matched normal children were taken as the control group. The mean basal-Zn excretion of the patients was significantly higher than the mean Zn excretion observed in controls. No significant difference is observed between the mean Zn excretion obtained on different doses of DF. However, they are both significantly higher than the mean basal-Zn levels of the controls.

Desferrioxamine induced urinary iron excretion in thalassemia.

Twenty one children of beta thalassemia major aged between 2 and 14 years of age on regular blood transfusion were given subcutaneous desferrioxamine. Their serum ferritin, 24 hours baseline urinary iron excretion and subcutaneous desferrioxamine induced urinary iron excretion were measured. The result showed a close correlation between serum ferritin and amount of blood transfusions received by the patient. There was good correlation between serum ferritin and desferrioxamine induced urinary iron excretion. A negative iron balance could be achieved in 15 out of 21 children with one dose of desferrioxamine therapy.