Renal dysfunction in patients with thalassaemia

Quinn, Charles T.; Johnson, Valerie; Kim, Hae-Young; Trachtenberg, Felicia; Vogiatzi, Maria; Kwiatkowski, Janet L.; Neufeld, Ellis J.; Fung, Ellen B.; Oliveri, N; Kirby, Melanie; Giardina, Patricia J.

doi:10.1111/j.1365-2141.2010.08477.x

Cited by 89 publications

(88 citation statements)

References 19 publications

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“…1 In b-thalassemia major (b-TM), regular transfusions of packed red blood cells are a mainstay of treatment but lead to iron overload. 2 As a result of chronic transfusions, iron deposition occurs in many organs, such as the liver, heart, and endocrine glands. 3 Due to the increase in patients' lifespan by early diagnosis, blood transfusions, and iron chelation therapy, previously unobserved associated disorders have been encountered in b-TM.…”

Section: Introductionmentioning

confidence: 99%

“…15 Few data are available regarding renal functional abnormalities in children with thalassemia. 2 There are very few studies that investigate renal dysfunction in patients with TM. 1,16 Moreover, we could not find any studies in the literature on urinary molecules indicative of early kidney injury, including NAG, NGAL, KIM-1, and L-FABP, in children with TM.…”

Section: Introductionmentioning

confidence: 99%

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Urinary early kidney injury molecules in children with beta-thalassemia major

et al. 2015

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Background: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in children with b-thalassemia major (b-TM). Materials and methods: Totally, 52 patients (29 boys, 23 girls) with b-TM and 29 healthy controls (3-17 years) were included. Various demographic characteristics and blood transfusions/year, disease duration, and chelation therapy were recorded. Serum urea, creatinine, electrolytes, and ferritin and urinary creatinine, protein, calcium, phosphorus, sodium, potassium, and uric acid in first morning urine samples were measured and estimated glomerular filtration rate (eGFR) was calculated. Routine serum and urinary biochemical variables, urinary NAG to Creatinine (U NAG/Cr ), U NGAL/Cr , U KIM-1/Cr , and U L-FABP/Cr ratios were determined. Results: Patients had similar mean serum urea, creatinine and eGFR levels compared with controls (p40.05 for all). The mean urinary protein to creatinine (U Protein/Cr ) ratio was significantly higher in patients compared to the healthy subjects (0.13 ± 0.09 mg/mg and 0.07 ± 0.04 mg/mg, respectively; p50.001). Significantly increased U NAG/Cr (0.48 ± 0.58 vs. 0.23 ± 0.16, p ¼ 0.026) and U NGAL/Cr (22.1 ± 18.5 vs. 11.5 ± 6.17, p ¼ 0.01) ratios were found in b-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or U KIM-1/Cr and U L-FABP/Cr ratios between patients and controls (p40.05). Significant correlations were found between urinary biomarkers and urinary electrolytes (p50.05). Conclusions: Our results suggest that urinary NAG and NGAL may be considered to be reliable markers to monitor renal injury in b-TM patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Urinary early kidney injury molecules in children with beta-thalassemia major

et al. 2015

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“…In patients with b-thalassemia who do not receive regular transfusion therapy (patients with b-thalassemia intermedia), creatinine clearance and GFR are increased. 20 Anemia may reduce systemic vascular resistance, leading to a hyperdynamic circulation that increases renal plasma flow and GFR. 21 These changes can eventually lead to stretching of the glomerular capillary wall and subsequent endothelial and epithelial injury, together with transudation of macromolecules into the mesangium associated with glomerular dysfunction.…”

mentioning

confidence: 99%

Mechanisms of Renal Disease in β-Thalassemia

Musallam

Taher

2012

Journal of the American Society of Nephrology

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Although advances in the care of patients with b-thalassemia translate into better patient survival, this success has allowed previously unrecognized complications to emerge, including several renal abnormalities. Clinical studies continue to show that mild tubular dysfunction and abnormalities in GFR are common in patients with b-thalassemia. Chronic anemia and iron overload are believed to lie behind these abnormalities. Nonprogressive increases in levels of serum creatinine have also been observed after exposure to some iron chelators. Longitudinal studies are needed to understand the true burden of renal dysfunction in patients with b-thalassemia.

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“…A recent cross-sectional study in TM patients has shown an abnormally high creatinine clearance in 20.8%, low creatinine clearance in 7.8%, hypercalciuria in 28.7%, and albuminuria in up to 59% of patients. 315 Mechanisms of kidney dysfunction are numerous and only partially clarified, but chronic anemia, hypoxia, iron, and iron chelators are potentially toxic to renal parenchyme. 316 Acute kidney injury has also been reported, and the probable mechanism in many cases is prerenal from sepsis or complications of HF (cardiorenal syndrome) and liver failure that affects renal perfusion.…”

Section: Renal Diseasementioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

310

165

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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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Renal dysfunction in patients with thalassaemia

Cited by 89 publications

References 19 publications

Urinary early kidney injury molecules in children with beta-thalassemia major

Urinary early kidney injury molecules in children with beta-thalassemia major

Mechanisms of Renal Disease in β-Thalassemia

Cardiovascular Function and Treatment in β-Thalassemia Major

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