Renal tubular function in β-thalassemia

Sumboonnanonda, Achra; Malasit, Prida; Tanphaichitr, Voravarn S.; Ong-Ajyooth, S; Sunthornchart, Sunthorn; Pattanakitsakul, Sa-Nga; Petrarat, Siripan; Assateerawatt, Amara; Vongjirad, A

doi:10.1007/s004670050453

Cited by 72 publications

(89 citation statements)

References 15 publications

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“…1 Although major system dysfunctions, including cardiopulmonary and reticuloendothelial systems, have been reported in patients with TM, little information is available on renal involvement. 4 In recent years, some studies have investigated renal proximal tubular damage using biomarkers including b2 microglobulin, N-acetyl-D-glucosaminidase (NAG), proteinuria, and aminoaciduria in thalassemia patients. 5,6 Moreover, a number of studies showed that patients with TM had increased urinary excretion of calcium, phosphate, magnesium, and uric acid.…”

Section: Introductionmentioning

confidence: 99%

“…Our finding of higher ratios of U Protein/Cr in patients is in accordance with these prior reports. 4,5,22,23 This proteinuria might be explained primarily by the impairment of proximal tubular reabsorption, which may be due to severe iron overload in the tissues where it also stimulates the production of reactive oxygen radicals and results in cellular injury. 24 As urinary protein/Cr ratio is 0.13 in our study, this degree of proteinuria is consistent with proximal tubular injury.…”

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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%

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confidence: 99%

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

et al. 2015

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“…(6,10) Furthermore, serum creatinine is notoriously unreliable as a marker of kidney function, and previous studies have reported normal creatinine levels in bthalassemia major patients with early tubular and glomerular dysfunction. (8,9,11,12) Our patient had evidence of proximal tubular dysfunction on deferasirox with generalized aminoaciduria, glycosuria, detection of urine protein, and elevated urine b2-microglobulin levels. Furthermore, cessation of deferasirox was followed by normalization of urinary amino acid, protein, and glucose excretion.…”

Section: Discussionmentioning

confidence: 73%

“…(6)(7)(8) The underlying cause for renal abnormalities is controversial but has been associated with chronic hypoxia related to anemia, (8,9) oxidative stress (9,10) and DFO. (6,10) Furthermore, serum creatinine is notoriously unreliable as a marker of kidney function, and previous studies have reported normal creatinine levels in bthalassemia major patients with early tubular and glomerular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

Milat

Wong

Fuller

et al. 2011

Journal of Bone and Mineral Research

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Patients with b-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade 1 ), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi Syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy. ß

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“…8 An association between an immunodeficiency and Fanconi syndrome has not been reported, though there are a few reports of renal tubular defects associated with hemoglobinopathies. 9,10 The pathogenesis of tubular dysfunction described in patients with ␤-thalassemia/HbE disease 9,10 may also apply to other anemic states. In various forms of thalassemia shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are contributing factors to functional and physiological abnormalities.…”

Section: Discussionmentioning

confidence: 99%

An infant with severe combined immunodeficiency syndrome, an α-thalassemia trait and renal Fanconi syndrome

Moesdijk

Weel-Sipman

2000

Bone Marrow Transplant

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Summary:We describe an infant with severe combined immunodeficiency syndrome and an ␣-thalassemia trait who developed a renal Fanconi syndrome after his first stem cell transplantation. This syndrome consists of a generalized failure of proximal tubular reabsorption, which leads to a large number of metabolic disturbances. The etiology varies from inherited causes, including an idiopathic form, to acquired causes such as intoxications, immunological disorders and hemoglobinopathies. In this case report we discuss possible explanations of the Fanconi syndrome in our patient. Bone Marrow Transplantation (2000) 26, 97-99. Keywords: immunodeficiency; ␣-thalassemia; bone marrow transplantation; Fanconi syndromeThe de Toni-Debré-Fanconi syndrome is characterized by a general dysfunction of the proximal tubule, leading to an excessive urinary loss of amino acids, glucose, bicarbonate, phosphate and other solutes normally absorbed in the proximal tubule. The consequences of these losses are hyperchloremic metabolic acidosis, decreased plasma phosphate levels, electrolyte imbalance, which can lead to severe dehydration, rickets, and growth retardation. The syndrome was first described by Lignac in 1924.1 In 1943, McCune et al 2 abbreviated the name to Fanconi syndrome. We describe a boy with severe combined immunodeficiency syndrome (SCID), ␣ 0 -thalassemia and Fanconi syndrome, a combination of rare diseases not previously reported. Case reportA 1-month-old Turkish boy, born 20 March 1998, was admitted to our hospital in April 1998 for a cord blood transplantation from a matched unrelated donor for his RAG-2 point mutation (deletion of a guanin nucleotide at position 1913, which causes a frame shift and a stop codon at amino acid position 247) autosomal recessive SCID (non T, non B). He was born after an uneventful pregnancy and delivery from consanguineous parents (first cousins), who lost their first born female child, also affected by SCID without signs of Fanconi syndrome. The diagnosis of our patient was established from cord blood. The father was heterozygous for ␣-thalassemia (--SEA) and the mother was heterozygous for ␤-thalassemia (IVS1-6 T→C). Hbelectrophoresis of blood from our patient revealed only an ␣-thalassemia trait. He was prepared for stem cell transplantation with antithymocytic globulin 5 mg/kg/day (20 mg/day) for 5 consecutive days because of circulating maternal T cells. He received cyclosporin A to prevent GVHD. On 25 May 1998, he received 80 ml MUD-cord blood without T or B cell depletion, which contained 15.2 ϫ 10 7 NBC/kg body weight. After stem cell transplantation he was treated with methotrexate 2.5 mg/day on days ϩ1 and ϩ3 and cyclosporin A was continued for GVHD prophylaxis. There were no complications during his hospital stay. Unfortunately, no engraftment of T or B cells was documented. He remained in good physical condition with length and weight measurements at the 10th percentile. In December 1998 he received a second stem cell transplant. This time he received bone marrow from a ma...

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Renal tubular function in β-thalassemia

Cited by 72 publications

References 15 publications

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

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

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

An infant with severe combined immunodeficiency syndrome, an α-thalassemia trait and renal Fanconi syndrome

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