Abstract
In order to assess the oxidative stress in newly diagnosed children with primary nephrotic syndrome (PNS), we serially measured serum total antioxidant capacity (TAC) and malondialdehyde (MDA) in 33 children with PNS and ten healthy matched controls. Patients were classified into two groups: those who had steroid-sensitive nephrotic syndrome (SSNS; n = 26) and those who had steroid-resistant nephrotic syndrome (SRNS; n = 7). Of the patients with SSNS, 15 were non-relapsers and 11 were relapsers. At the proteinuric phase, all patients had significantly higher MDA levels and lower TAC than the controls. These changes were more marked in patients with SRNS than in those with SSNS. During remission and still on corticosteroids, patients had higher TAC and similar MDA levels as in the proteinuric phase, but the TAC and MDA levels still significantly differed from those of the controls. More improvement in TAC and MDA levels occurred in patients following the weaning of corticosteroids, but TAC was still lower in the patients than in the controls. Moreover, TAC was higher in non-relapsers than in relapsers. Using a receiver operating characteristic curve, the initial response to corticosteroids could be predicted at serum TAC level ≥0.73 mM/L (sensitivity 89%, specificity 86%), while serum TAC levels ≤ 1.14 mM/L after the weaning of corticosteroids could predict that the patient would not relapse (sensitivity 91%, specificity 80%). In conclusion, based on our results, PNS can be considered to be associated with oxidative stress even during remission. This stress may modulate the response to corticosteroids. Further prospective studies using larger numbers of patients are needed to validate these results.
References
Valenzuela A (1991) The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 48:301–309
McCord JM (2000) The evolution of free radicals and oxidative stress. Am J Med 108:652–659
Pedraza-Chaverri J, Arevalo AE, Hernandez-Pando R, Larriva-Sahd J (1995) Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome. Int J Biochem Cell Biol 27:683–691
Ohtake T, Kimura M, Nishimura M, Hishida A (1997) Roles of reactive oxygen species and antioxidant enzymes in murine daunomycin-induced nephropathy. J Lab Clin Med 129:81–88
Clemens MR, Burza-Zanetti Z (1989) Lipid abnormalities and peroxidation of erythrocytes in nephrotic syndrome. Nephron 53:325–329
Ginevri F, Ghiggeri GM, Candiano G, Oleggini R, Bertelli R (1989) Peroxidative damage of erythrocyte membrane in children with nephrotic syndrome. Pediatr Nephrol 3:25–32
Warwick G, Waller H, Ferns G (2000) Antioxidant vitamin concentrations and LDL oxidation in nephrotic syndrome. Ann Clin Biochem 37:488–491
International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome for initial response to prednisone. J Pediatr 98:561–564
Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V (2001) Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 54:356–361
Satoh K (1978) Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 90:37–43
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Zachwieja J, Bobkowski W, Dobrowolska-zachwieja A, Zaniew M, Maciejewski J (2003) Decreased antioxidant activity in hypercholesterolemic children with nephrotic syndrome. Med Sci Monit 9:235–239
Ece A, Atamer Y, Gurkan F, Davutoglu M, Kocyigit Y, Tutanc M (2005) Paraoxonase, total antioxidant response, and peroxide levels in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20:1279–1284
Karthikeyan K, Sinha I, Prabhu K, Bhaskaranand N, Rao A (2008) Plasma protein thiols and total antioxidant power in pediatric nephrotic syndrome. Nephron Clin Pract 110:c10–c14
Mathew JL, Kabi BC, Rath B (2002) Anti-oxidant vitamins and steroid responsive nephrotic syndrome in indian children. J Paediatr Child Health 38:450–454
Balamurgan R, Bobby Z, Selvaraj N, Nalini P, Koner BC, Sen SK (2003) Increased protein glycation in non-diabetic pediatric nephrotic syndrome: possible role of lipid peroxidation. Clin Chim Acta 337:127–132
Ece A, Atamer Y, Gurkan F, Balici M, Kocyigit Y (2004) Antioxidant status in relation to lipoproteins, leptin and pro-inflammatory cytokines in children with steroid sensitive nephrotic syndrome. J Nephrol 9:336–373
Gusmano R, Ginevri F, Ghiggeri GM, Perfumo F, Oleggini R, Candiano G, Bertelli R, Piccardo MT (1988) Intraerytrocytary markers of peroxidative alteration in children with nephrotic syndrome. Contrib Nephrol 67:99–102
Kinra S, Rath B, Kabi BC (2000) Indirect quantification of lipid peroxidation in steroid responsive nephrotic syndrome. Arch Dis Child 82:76–78
Moran EC, Kamiguti AS, Cawley JC, Pettitt AR (2002) Cytoprotective antioxidant activity of serum albumin and autocrine catalase in chronic lymphocytic leukaemia. Br J Haematol 116:316–328
Zachwieja J, Bobkowski W, Dobrowolska-Zachwieja A, Zaniew M, Maciejewski J (2001) Dietary intake of antioxidants and antioxidant status in nephrotic syndrome. Pol Merk Lek 58:237–240
Baliga R, Baliga M, Shah SV (1992) Effect of selenium deficient diet in experimental glomerular disease. Am J Physiol 263:56–61
Trevisan R, Dodesini A, Lepore G (2006) Lipids and renal disease. J Am Soc Nephrol 17:145–147
Nagla T, Nagwa A, Mohamed M (2008) Oxidative modification of low-density lipoprotein in relation to dyslipidemia and oxidant status in children with steroid sensitive nephrotic syndrome. Pediatr Res 63:404–409
Kawamura T, Yoshiok T, Bills T, Fogo A (1991) Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. Kidney Int 40:291–301
Zachwieja J, Bobkowski W, Zaniew M, Dobrowolska-Zachwieja A, Lewandowska-Stachowiak M, Siwinska A (2003) Apoptosis and antioxdant defense in the nephrotic syndrome. Pediatr Nephrol 18:1116–1121
Fydryk J, Jacobson E, Kurzawska O, Malecka G, Gonet B, Urasinski T, Brodkiewicz A, Bokowska H (1998) Antioxidant status of children with steroid sensitive nephrotic syndrome. Pediatr Nephrol 12:751–754
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Bakr, A., Abul Hassan, S., Shoker, M. et al. Oxidant stress in primary nephrotic syndrome: does it modulate the response to corticosteroids?. Pediatr Nephrol 24, 2375–2380 (2009). https://doi.org/10.1007/s00467-009-1246-2
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DOI: https://doi.org/10.1007/s00467-009-1246-2