Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy

Cianciulli, Paolo; Sollecito, Daniela; Sorrentino, Francesco; Forte, Laura; Gilardi, E.; Massa, A.; Papa, G; Carta, Salvatore

doi:10.1038/ki.1994.295

Cited by 48 publications

(35 citation statements)

References 9 publications

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“…2 The relationship between urinary N-acetyl-D-glucosaminidase and creatinine (U NAG/Creatinine ) and total amount of transfused iron in patients with thalassemia distal tubules was found in 18 autopsied thalassemic patients by Landing et al [13]. Later, several studies describing renal function disturbances in patients with thalassemia major were published [8,9,14]. Comparing blood biochemistry and urinalysis in patients with β-thalassemia major and thalassemia intermedia, Ali et al recently reported that hyperuricemia and microscopic hematuria are more common in thalassemia intermedia than in thalassemia major [15].…”

Section: Discussionmentioning

confidence: 95%

Renal function in children with β-thalassemia major and thalassemia intermedia

et al. 2008

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In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (U(NAG)) and beta2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with beta-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with beta-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. U(NAG) and U(NAG) to creatinine ratio (U(NAG/CR)) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with beta- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.

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Section: Discussionmentioning

confidence: 95%

Renal function in children with β-thalassemia major and thalassemia intermedia

et al. 2008

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“…In 1998, Lena evaluated the rate of proteinuria, aminoaciduria, urine osmolality and electrophoresis of urinary proteins in 95 thalassemia patients in Thailand and found that excretion of urinary NAG and B 2 microglobulin was markedly higher in these patients than in the control group [1]. Cianciulli and colleagues evaluated renal function in 19 beta-thalassemia patients in Italy and found evidence of renal tubular damage in 13 patients [9]. Sumboonnanonda et al in a similar study demonstrated the renal function of 34 alpha-thalassemia patients and found that levels of urinary NAG, B 2 microglobulin and malondialdehyde (MDA) were elevated in this group relative to the controls.…”

Section: Discussionmentioning

confidence: 97%

Early markers of renal dysfunction in patients with beta-thalassemia major

et al. 2008

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Studies of renal involvement in thalassemia syndromes have been varied and few. The most important cause of mortality and morbidity in these patients is organ failure due to iron deposition. We report here a cross-sectional study carried out between February 2005 and February 2006 on all beta-thalassemia major patients being treated in Mofid Children's hospital, Tehran. The aim of the study was to detect renal dysfunction in these patients. The patient cohort consisted of 103 patients with various disease severities. Fresh first morning urine samples were collected and analyzed for sodium (Na), potassium (K), calcium (Ca), creatinine (Cr), phosphate, uric acid (UA), N-acetyl beta-D-glucosaminidase (NAG) and amino acids. We also carried out a complete blood count evaluation and assayed fasting blood sugar and serum ferritin, sodium, potassium, creatinine, uric acid and amino acids in all patients. The mean age of our patient cohort was 12.5+/-5.53 years and 53.4% were female. Abnormal levels of urinary NAG were detected in 35.9% of patients (confidence interval 26-45%). Abnormal levels of fractional excretion (FE)-Na, FE-K and FE-UA and abnormal urine protein Pr/Cr and urine Ca/Cr ratios were present in 29.1, 7.8, 52.4, 0.3 and 22.3% of the patients, respectively. There was a significant relationship between urinary NAG and the age of the patient (R=0.35), duration of deferoxamine therapy (R= 0.31), duration of receiving blood transfusions (R=0.34) and level of fasting blood sugar (R=0.2). We concluded that renal disorders are not rare in patients with beta-thalassemia major and that they may increase in terms of frequency with age, increased duration of transfusion and deferoxamine usage and high levels of blood sugar.

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“…Deferoxamine causes acute renal dysfunction at high doses or at normal doses in high-risk patients (those with diabetes mellitus, hypertension, or proteinuria; elderly patients; and those with underlying renal dysfunction), especially when given intravenously. [319][320][321] Deferasirox has been associated with several renal side effects, including nonprogressive increases in serum creatinine and cases of reversible mild or even life-threatening Fanconi syndrome.…”

Section: Renal Diseasementioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

332

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy

Cited by 48 publications

References 9 publications

Renal function in children with β-thalassemia major and thalassemia intermedia

Renal function in children with β-thalassemia major and thalassemia intermedia

Early markers of renal dysfunction in patients with beta-thalassemia major

Cardiovascular Function and Treatment in β-Thalassemia Major

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