Study of Urinary Alpha Glutathione-S-Transferase in Children with Idiopathic Nephrotic Syndrome
Abstract
Glomerulopathy associated with recurrent or persistent proteinuria may lead to progressive tubulointerstitial fibrosis. Early detection of tubulointerstitial fibrosis may result in a more favorable outcome of chronic kidney disease (CKD) because nephroprotective treatment may be instituted in due course. One of the early markers of tubulointerstitial fibrosis is glutathione S-transferase (GST). The aim of this study was to determine urinary alpha-GST in children with idiopathic nephrotic syndrome (INS), either in remission or relapse. This case–control study included 40 children with primary nephrotic syndrome (NS), either in remission or relapse. Also, 40 healthy children, age- and sex-matched as controls, were selected from the outpatients and the pediatric nephrology unit of Al-Zahraa Hospital, Al-Azhar University. Urinary alpha-GST was investigated in the study groups on the same lines as that of routine investigations of INS. Children with INS have significantly higher urinary GST either in remission or relapse, it was (5.23 ± 1.90) ng/mL, (5.32 ± 1.52) ng/mL respectively compared with healthy controls, it was (2.59 ± 1.12) ng/mL with (P = 0.001). A positive correlation between urinary alpha-GST and body weight BW, height, body mass index (BMI), white blood cells (WBCs) count, erythrocyte sedimentation rate, serum (cholesterol, triglyceride [TG]) level, blood urea nitrogen (BUN), and duration of the disease. Urinary alpha-GST was increased in children with NS even after remission, and it consequently led to oxidative stress and tubulointerstitial fibrosis. Nephroprotective treatment is recommended even in cases with INS, either in remission or relapse.
Keywords
How to Cite
References
Ray R, Sharma A, Gupta R, Bagga A, Dinda AK. Peritubular capillaries and renal function in pediatric idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl. 2013;24(5):942–9. 10.4103/1319-2442.118091
Bienias´ B, Zajaczkowska M, Borzecka H, et al. Early markers of tubulointerstitial fibrosis in children with idiopathic nephrotic syndrome. Medicine, 2015; 94(42):e1746.
Susantitaphong P, Perianayagam MC, Tighiouart H. Urinary α-and π-glutathione s-transferases for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers. 2013;18:331–7. 10.3109/1354750X.2013.781678
Sundberg AG, Appelkvist EL, Backman L, Dallner G. Urinary pi-class glutathione transferase as an indicator of tubular damage in the human kidney. Nephron. 1994;67:308–16. 10.1159/000187985
Dieterle F, Sistare F. Biomarkers of acute kidney injury. In: Vaidya VS, Bonventre JV, editors. Biomarkers: In medicine, drug discovery, and environmental Health. Hoboken: Wiley. p. 237–79.
Ferri F. Nephrotic syndrome In: Ferri’s Clinical Advisor, New York: Elsevier Health Sciences US; 2016. p. 866.
Turner N. The patient with glomerular disease. In: Winearls C, Goldsmith D, Hornblower S, eds. Oxford textbook of clinical nephrology. 4th ed. Oxford University Press; 2015. p. 502–29.
Priyanka R, Seema PS, Rathika DS, et al. v Oxidative stress in childhood steroid sensitive nephrotic syndrome and its correlation with DNA damage International Journal of Complementary Pediatrics. 2016;3(3):768–772.
Board PG, Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim Biophys Acta. 2013;1830:3267–88. 10.1016/j.bbagen.2012.11.019
Allen EM, Mieyal JJ. Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins. Antioxid Redox Signal. 2012;17:1748–1763. 10.1089/ars.2012.4644
Lillig CH, Berndt C. Glutaredoxins in thiol/disulfide exchange. Antioxid Redox Signal. 2013;18:1654–65. 10.1089/ars.2012.5007
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88. 10.1146/annurev.pharmtox.45.120403.095857
Frova C. Glutathione transferases in the genomics era: New insights and perspectives. Biomol Eng. 2006;23:149–69. 10.1016/j.bioeng.2006.05.020
Marnett LJ, Riggins JN, West JD. Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein. J Clin Invest. 2003;111:583–93. 10.1172/JCI200318022
Fan A, Jiang X, Mo Y, Tan H, Jiang M, Li J. Plasma levels of oxidative stress in children with steroid-sensitive nephrotic syndrome and their predictive value for relapse frequency. Pediatr Nephrol. 2016;31(1):83–8. 10.1007/s00467-015-3195-2
Abbate M, Zaja C, Remuzzi G. Proteinuria cause progressive renal damage. Ospedali Riuniti di Bergamo, Italy: Mario Negri Institute for Pharmalogical Research and Unit of Nephrology and Dialysis, Azienda Ospedaliera; 2006.
Paul AG, Matthew JP, Timothy JG, David AB. Carbonylation of adipose proteins in obesity and insulin resistance, identification of adipocyte fatty acid binding protein as a cellular target of 4-hydroxynonenal. Mol Cell Proteom. 2007;6:624–37. 10.1074/mcp.M600120-MCP200
Ozaydin A, Onaran I, Yesim TE, Sargın H, Avsar K, Sultuybek G. Increased glutathione conjugate transport: A possible compensatory protection mechanism against oxidative stress in obesity? Int J Obes. 2006;30:134–40. 10.1038/sj.ijo.0803108
Liu J, Ma KL, Gao M, Wang CX, Ni J, Zhang Y. et al. Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients. PLoS One. 2012;7:e47217. 10.1371/journal.pone.0047217
Ni J, Ma KL, Wang CX, Liu J, Zhang Y, Lv LL, et al. Activation of renin-angiotensin system is involved in dyslipidemia-mediated renal injuries in apolipoprotein E knockout mice and HK-2 cells. Lipids Health Dis. 2013;12:49. 10.1186/1476-511X-12-49
Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med. 2015;21:37–46. 10.1038/nm.3762
Niki E. Lipid peroxidation products as oxidative stress biomarkers. Biofactors. 2008;34(2):171–80. 10.1002/biof.5520340208
Bashir M, Cawood T, O’Shea D, et al. Obesity-related nephropathy: Evidence of proximal tubular damage. Endocr Abstr. 2008;15:123.
Cawood TJ, Bashir M, Brady J, et al. Urinary collagen IV and πGST: Potential biomarkers for detecting localized kidney injury in diabetes-a pilot study. Am J Nephrol. 2010;32:219–25. 10.1159/000317531
Palm F, Nordquist L. Renal oxidative stress, oxygenation and hypertension. Uppsala, Sweden: Department of Medical Biology, Uppsala University and Washington, DC: Division of Nephrology and Hypertension Georgetown University; 2011.
Copyright and licence
Copyright (c) 2020 Manal Abdel-Salam, Houriah Ahmed Allam, Shams Kholoussi, Asmaa Abd El-Wakeel Ibrahim, Shaimaa Adel Abd El-Hakeim

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

