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Italian Journal of Pediatrics
Published in: Italian Journal of Pediatrics 1/2010

Open Access 01-12-2010 | Research

Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study

Authors: Enas A Hamed, Nagla T ElMelegy

Published in: Italian Journal of Pediatrics | Issue 1/2010

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Abstract

Background

In β-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in β-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependant beta-thalassemia major (TD-βTM), using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy.

Methods

Sixty-nine TD-βTM patients (aged 1-16 years) and 15 healthy controls (aged 3-14 years) were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO), patients were divided into two groups: group [I] with chelation (n = 34) and group [II] without chelation (n = 35). Levels of creatinine (Cr), calcium (Ca), inorganic phosphorus (PO4), uric acid (UA) and albumin were measured by spectrophotometer. Serum (S) levels of cystatin-C (SCysC) and total antioxidant capacity (STAC) and urinary (U) levels of β2-microglobulin (Uβ2MG) were measured by immunosorbent assay (ELISA). Urinary N-acetyl-beta-D-glucosaminidase (UNAG) activity and malondialdehyde (UMDA) were measured by chemical methods. Estimated glomerular filtration rate (eGFR) was determined from serum creatinine.

Results

In patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated SUA, SPO4, UNAG/Cr, Uβ2MG/Cr] and oxidative stress marker disturbances [diminished STAC and elevated UMDA/Cr] were reported than controls. In patients with chelation, SCysC was significantly higher while, STAC was significantly lower than those without chelation. In all patients, SCysC showed significant positive correlation with SCr and negative correlation with eGFR; STAC showed significant positive correlation with eGFR and negative correlation with SCysC, SCr, UNAG/Cr; UMDA/Cr showed significant positive correlation with Ualbumin/Cr, Uβ2MG/Cr, UNAG/Cr.

Conclusions

Our data confirm high frequency of glomerular and tubular dysfunctions in TD-βTM pediatric patients which could be attributed to oxidative stress and DFO therapy.
Literature
1.
Mastrangelo F, Lopez T, Rizzelli S, Manisco G, Corliano C, Alfonso L: Function of the kidney in adult patients with Cooley's disease. A preliminary report. Nephron. 1975, 14: 229-236. 10.1159/000180452.PubMedCrossRef
2.
Shehab M, Barakat AY: Thalassemia B with distal renal tubular acidosis: a previously undescribed association. Int J Pediatr Nephrol. 1985, 6: 143-144.PubMed
3.
Ong-ajyooth L, Malasit P, Ong-ajyooth S, Fucharoen S, Pootrakul P, Vasuvattakul S, Siritanaratkul N, Nilwarangkur S: Renal function in adult beta thalassemia/Hb E disease. Nephron. 1998, 78: 156-161. 10.1159/000044904.PubMedCrossRef
4.
Sumboonnanonda A, Malasit P, Tanphaichitr VS, Ong-ajyooth S, Sunthornchart S, Pattanakitsakul S, Petrarat S, Assateerawatt A, Vongjirad A: Renal tubular function in beta-thalassemia. Pediatr Nephrol. 1998, 12: 280-283. 10.1007/s004670050453.PubMedCrossRef
5.
Aldudak B, Karabay Bayazit A, Noyan A, Ozel A, Anarat A, Sasmaz I, KilinC Y, Gali E, Anarat R, Dikmen N: Renal function in pediatric patients with β-thalassemia major. Pediatr Nephrol. 2000, 15: 109-112. 10.1007/s004670000434.PubMedCrossRef
6.
Koren G, Kochavi-Atiya Y, Bentur Y, Olivieri NF: The effects of subcutaneous deferoxamine administration on renal function in thalassemia major. Int J Hematol. 1991, 54: 371-375.PubMed
7.
Cianciulli P, Sollecito D, Sorrentino F, Forte L, Gilardi E, Massa A, Papa G, Carta S: Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy. Kidney Int. 1994, 46: 467-470. 10.1038/ki.1994.295.PubMedCrossRef
8.
Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T: Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer. 2006, 47 (1): 71-76. 10.1002/pbc.20645.PubMedCrossRef
9.
Galteau MM, Guyon M, Gueguen R, Siest G: Determination of serum cystatin C: biological variation and reference values. Clin Chem Lab Med. 2001, 39: 850-857. 10.1515/CCLM.2001.141.PubMedCrossRef
10.
Schwartz G, Brion L, Spitzer A: The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am. 1987, 34: 571-590.PubMed
11.
Stevens LA, Levey AS: Measurement of kidney function. Med Clin N Am. 2005, 89: 457-473. 10.1016/j.mcna.2004.11.009.PubMedCrossRef
12.
Hemmingsen I, Skaarup P: β2-Microglobulin in urine and serum determined by ELISA technique. Scand J Clin Invest. 1985, 45: 367-371. 10.3109/00365518509161020.PubMedCrossRef
13.
Maruhn D: Rapid colorimetric assay of β-galactosidase and N-acetyl-β-D-glucosaminidase in human urine. Clinica Chimica Acta. 1976, 73: 453-461. 10.1016/0009-8981(76)90147-9.CrossRef
14.
Miller N, Rice-Evans C, Davies MJ, Gopinathan V, Milner A: Replacement of metmyoglobin as a peroxidase source by horse radish peroxidase. Clin Sci. 1993, 84: 407-412.PubMedCrossRef
15.
Buege JA, Aust SD: Microsomal lipid peroxidation modified by adding the BHT solution to prevent further lipid peroxidation during boiling. Methods Enzymology. 1978, 52: 302-310. full_text.CrossRef
16.
Michelakakis H, Dimitriou E, Georgakis H, Karabatsos F, Fragodimitri C, Saraphidou J, Premetis E, Karagiorga-Lagana M: Iron overload and urinary lysosomal enzyme levels in beta-thalassemia major. Eur J Pediatr. 1997, 156: 602-604. 10.1007/s004310050673.PubMedCrossRef
17.
Koliakos G, Papachristou F, Koussi A, Perifanis V, Tsatra I, Souliou E, Athanasio M: Urine biochemical markers of early renal dysfunction are associated with iron overload in b-thalassaemia. Clin Lab Haem. 2000, 25: 105-109. 10.1046/j.1365-2257.2003.00507.x.CrossRef
18.
Grundy RG, Woods KA, Savage MO, Evans JP: Relationship of endocrinopathy to iron chelation status in young patients with thalassaemia major. Arch Dis Child. 1994, 71 (2): 128-132. 10.1136/adc.71.2.128.PubMedCentralPubMedCrossRef
19.
Li Volti S, Di Gregorio F, Schiliro G: Acute changes in renal function associated with deferoxamine therapy. Am J Dis Child. 1990, 144: 1069-1070.PubMed
20.
Cordeiro VF, Pinheiro DCSN, Silva GB, Lima JWQ, Mota RMS, Libório AB, Daher EF: Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children. Clinica Chimica Acta. 2008, 391: 46-50. 10.1016/j.cca.2008.02.004.CrossRef
21.
Helin I, Axenram M, Grubb A: Serum cystatin C as a determinant of glomerular filtration rate in children. Clin Nephrol. 1998, 49 (4): 221-225.PubMed
22.
Mohkam M, Shamsian BS, Gharib A, Nariman S, Arzanian MT: Early markers of renal dysfunction in patients with beta thalassemia major. Pediatr Nephrol. 2008, 23: 971-976. 10.1007/s00467-008-0753-x.PubMedCrossRef
23.
Katopodis KP, Elisaf MS, Pappas HA, Theodorou JC, Milionis HJ, Bourantas KL, Siamopoulos KC: Renal abnormalities in patients with sickle cell-beta thalassemia. J Nephrol. 1997, 10: 163-167.PubMed
24.
Dharnidharka VR, Kwon C, Stevens G: Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002, 40: 221-226. 10.1053/ajkd.2002.34487.PubMedCrossRef
25.
Filler G, Bökenkamp A, Hofmann W, Le Bricon T, Martínez-Brú C, Grubb A: Cystatin C as a marker of GFR history, indications, and future research. Clin Biochem. 2005, 38: 1-8. 10.1016/j.clinbiochem.2004.09.025.PubMedCrossRef
26.
Tanaka A, Suemaru K, Araki H: A new approach for evaluating renal function and its practical application. J Pharmacol Sci. 2007, 105: 1-5. 10.1254/jphs.CP0070058.PubMedCrossRef
27.
Voskaridou E, Terpos E, Michail S, Hantzi E, Anagnostopoulos A, Margeli A, Simirloglou D, Loukopoulos D, Papassotiriou I: Early markers of renal dysfunction in patients with sickle cell/beta-thalassemia. Kidney Int. 2006, 69: 2037-2042. 10.1038/sj.ki.5000248.PubMedCrossRef
28.
Economou M, Printza N, Teli A, Tzimouli V, Tsatra I, Papachristou F, Athanassiou-Metaxa M: Renal Dysfunction in Patients with Beta-Thalassemia Major Receiving Iron Chelation Therapy either with Deferoxamine and Deferiprone or with Deferasirox. Acta Haematol. 2010, 123 (3): 148-152. 10.1159/000287238.PubMedCrossRef
29.
MacDonald J, Marcora S, Jibani M, Roberts G, Kumwenda M, Glover R, Barron J, Lemmey A: GFR estimation using cystatin C is not independent of body composition. Am J Kidney Dis. 2006, 48: 712-719. 10.1053/j.ajkd.2006.07.001.PubMedCrossRef
30.
Lapatsanis P, Sbyrakis S, Vertos C, Karaklis BA, Dosiadis S: Phosphaturia in thalassemia. Pediatrics. 1976, 58: 885-885.PubMed
31.
Smolkin V, Halevy R, Levin C, Mines M, Sakran W, Ilia K, Koren A: Renal function in children with β-thalassemia major and thalassemia intermedia. Pediatr Nephrol. 2008, 23: 1847-1851. 10.1007/s00467-008-0897-8.PubMedCrossRef
32.
Sikora P, Glatz S, Beck BB, Stapenhorst L, Zajaczkowska M, Hesse A, Hoppe B: Urinary NAG in children with urolithiasis, nephrocalcinosis, or risk of urolithiasis. Pediatr Nephrol. 2003, 18: 996-999. 10.1007/s00467-003-1229-7.PubMedCrossRef
33.
Herrero-Morin JD, Malaga S, Fernandez N, Rey C, Diéguez MA, Solis G, Concha A, Medina A: Cystatin C and beta-2-microglobulin: markers of glomerular filtration in critically ill children. Crit Care. 2007, 11: R59-R66. 10.1186/cc5923.PubMedCentralPubMedCrossRef
34.
Portman RJ, Kissane JM, Robson AM: Use of beta-2-microglobulin to diagnose tubulo-interstitial renal lesions in children. Kidney Int. 1986, 30: 91-98. 10.1038/ki.1986.156.PubMedCrossRef
35.
Guder WG, Hofmann W: Markers for the diagnosis and monitoring of renal tubular lesions. Clin Nephrol Suppl. 1992, 38: S3-S7.
36.
Prior RL, Cao G: In vivo total antioxidant capacity: comparison of different analytical methods. Free Radic Biol Med. 1999, 27: 1173-1181. 10.1016/S0891-5849(99)00203-8.PubMedCrossRef
37.
Koliakos G, Papachristou F, Koussi A, Perifanis V, Tsatra I, Souliou E, Athanasiou M: Urine biochemical markers of early renal dysfunction are associated with iron overload in beta-thalassaemia. Clin Lab Hematol. 2003, 25: 105-109. 10.1046/j.1365-2257.2003.00507.x.CrossRef
38.
Laksmitawati DR, Handayani S, Udyaningsih-Freisleben SK, Kurniati V, Adhiyanto C, Hidayat J, Kusnandar S, Dillon HS, Munthe BG, Wirawan R, Soegianto RR, Ramelan W, Frei sleben HJ: Iron status and oxidative stress in beta-thalassaemia patients in Jakarta. Biofactors. 2003, 19: 53-62. 10.1002/biof.5520190107.PubMedCrossRef
39.
Sumboonnanonda A, Malasit P, Tanphaichitr VS, Ong-ajyooth S, Petrarat S, Vongjirad A: Renal tubular dysfunction in alpha thalassemia. Pediatr Nephrol. 2003, 18: 257-260.PubMed
40.
Modell B, Khan M, Darlison M: Survival in beta-thalassemia major in the UK: data from the UK Thalassemia Register. Lancet. 2000, 355: 2051-2052. 10.1016/S0140-6736(00)02357-6.PubMedCrossRef
41.
Kontoghiorghes G, Neocleous K, Kolnagou A: Benefits and risks of deferiprone in iron overload in thalassemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Saf. 2003, 26: 553-584. 10.2165/00002018-200326080-00003.PubMedCrossRef
42.
Sirchia C, Zanella A, (Ed): A short guide to the management of thalassemia. Thalassemia Today. 2nd Mediteranean Meeting on Thalassemia: Centro Transfusionale Ospetale Maggiore Polyclinico di Milano. Italy: Milano. 1985, 635-663.
Metadata
Title
Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study
Authors
Enas A Hamed
Nagla T ElMelegy
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Italian Journal of Pediatrics / Issue 1/2010
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/1824-7288-36-39

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