ÇOCUKLARDA SERUM HOMOSİSTEİN DÜZEYİ İLE IgA NEFROPATİSİ ARASINDAKİ OLASI İLİŞKİ

Year 2021, , 568 - 573, 01.10.2021

Cemile Pehlivanoğlu , Zeynep Yuruk Yildirim , Alev Yılmaz , Asuman Gedikbaşı , Nurinisa Karagöz Nurver Akıncı Aysel Kıyak Gül Özçelik Yasemin Özlük , İşin Kılıçaslan , Ayşe Özağarı Bağdagül Yavaş Sevinç Emre

https://doi.org/10.26650/IUITFD.2021.847530

Abstract

Amaç: Deneysel ve epidemiyolojik çalışmalar, yüksek serum homosistein düzeylerinin renal hasara yol açabileceğini ve kronik böbrek hastalığı gelişimi için önemli bir risk faktörü olabileceğini göstermektedir. Çalışmamızın amacı IgA nefropatisi ve Henoch- Schönlein purpura nefriti olan hastalarda serum homosistein düzeyleri ile kresent oluşumu arasında bir ilişki olup olmadığını belirlemektir. Gereç ve Yöntemler: Üç pediatrik nefroloji merkezinde son beş yılda biyopsi ile IgA nefropatisi, Henoch-Schönlein purpura nefriti ve idiopatik kresentik glomerulonefrit tanısı alan 31 hasta ve 25 sağlıklı kontrol çalışmaya alındı. Bulgular: Hastaların homosistein düzeyleri normal değerin üst sınırından ve kontrollerden de daha yüksekti (p=0,0001). Biyopside kresent görülen ve görülmeyen hastalar arasında da homosistein düzeyleri açısından anlamlı fark yoktu (p>0,05). Proteinüri varlığı ve şiddeti ile homosistein düzeyleri arasında ilişki saptanmadı (p>0,05). Sonuç: Serum homosistein düzeyleri IgA nefropatisi ve Henoch- Schonlein purpura nefriti olan hastalarda yüksek bulunmuştur. Sonuçlarımız, bu hasta grubunda yüksek serum homosistein düzeylerinin segmental glomerüloskleroz ile ilişkili olabileceğini düşündürmektedir.

Keywords

IgA nefropatisi, homosistein, kresent

A POSSIBLE RELATIONSHIP BETWEEN SERUM HOMOCYSTEINE LEVEL AND IgA NEPHROPATHY IN CHILDREN

Abstract

Objective: The evidences from experimental and epidemiological studies suggests that elevated serum homocysteine levels may lead to renal injury and may be a significant risk factor for the development of chronic kidney disease. The aim of this study was to investigate a possible relationship between serum homocysteine level and crescent formation in children with IgA nephropathy and Henoch-Schonlein purpura nephritis. Material and Methods: A total of 31 patients diagnosed as biopsy proven IgA nephropathy and Henoch-Schonlein purpura nephritis and idiopathic crescentic glomerulonephritis in three Pediatric Nephrology centers within the last five years and 25 healthy controls were enrolled in the study. Results: Homocysteine levels of patients were higher than the upper limit of normal value and also higher than the controls (p=0.0001). There was no significant difference between the patients with or without crescent formation regarding homocysteine levels (p>0.05). Presence or severity of proteinuria was not related to homocysteine levels (p>0.05). Conclusion: Serum homocysteine levels are elevated in patients with IgA nephropathy and Henoch-Schonlein purpura nephritis. Our results suggest that elevated serum homocysteine levels may be related to segmental glomerulosclerosis in these patient groups.

Keywords

IgA nephropathy, homocysteine, crescent

References

• 1. Nakanishi K, Yoshikawa N. Immunoglobulin A Nephropathy. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL,editors. Pediatric Nephrology, 7th ed. Berlin Heidelberg: Springer-Verlag; 22016.pp983-1033.
• 2. Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, et al. Validity of the Oxford classification of IgA nephropathy in children. Pediatr Nephrol 2012;27(5):783-92. [CrossRef]
• 3. Coppo R, Davin JC. The difficulty in considering modifiable pathology risk factors in children with IgA nephropathy: crescents and timing of renal biopsy. Pediatr Nephrol 2014;30(2):189-92. [CrossRef]
• 4. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 2009;76(5):546-56. [CrossRef]
• 5. Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH, et.al. KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis. Am J Kidney Dis 2013;62(3):403-41. [CrossRef]
• 6. Kusano T, Takano H, Kang D, Nagahama K, Aoki M, Morita M, et al. Endothelial cell injury in acute and chronic glomerular lesions in patients with IgA nephropathy. Human Pathology 2015;49:135-44. [CrossRef]
• 7. Rodgers GM, Conn MT. Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. Blood 1990;75(4):895-901. [CrossRef]
• 8. Rodgers GM, Kane WH. Activation of endogenous factor V by homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986;77(6):1909-16. [CrossRef]
• 9. Tsai JC, Perrella MA, Yoshizumi M, Hsieh CM, Haber E, Schlegel R, et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci 1994;91(14):6369-73. [CrossRef]
• 10. Farid FA, Faheem MS, Heshmat NM, Shaheen KY, Saad SS. Study of the homocysteine status in children with chronic renal failure. Am J Nephrol 2004;24(3):289-95. [CrossRef]
• 11. Kumagai H, Katoh S, Hirosawa K, Kimura M, Hishida A, Ikegaya N. Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia. Kidney Int 2002;62(4):1219-28. [CrossRef]
• 12. Kanani PM, Sinkey CA, Browning RL, Allaman M, Knapp HR, Haynes WG. Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans. Circulation 1999;100(11):1161-8. [CrossRef]
• 13. Li N, Chen YF, Zou AP. Implications of hyperhomocysteinemia in glomerular sclerosis in hypertension. Hypertension 2002;39(2 Pt 2):443-8. [CrossRef]
• 14. Hwang SY, Woo CW, Au-Yeung KK, Siow YL, Zhu TY, O K. Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-kappaB activation. Am J Physiol Renal Physiol 2007;294(1):F236-44. [CrossRef]
• 15. Dillon MJ, Ozen S. A new international classification of childhood vasculitis. Pediatr Nephrol 2006;21(9):1219-22. [CrossRef]
• 16. Roberts IS. Pathology of IgA nephropathy. Nat Rev Nephrol 2014;10(8):445-54. [CrossRef]
• 17. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017;140(3): e20171904. [CrossRef]
• 18. Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20(3):629-37.[CrossRef]
• 19. Yap HK, Lau PY. Hematuria and Proteinuria. In: Geary FD, Schaefer F, editors. Comprehensive Pediatric Nephrology, 1st ed. Philadelphia: Mosby Elseiver; 2008.pp179-93. [CrossRef]
• 20. Nicholson JF, Pesce MA. Reference ranges for laboratory tests and procedures. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics, 17th ed. Philadelphia: Saunders; 2004.pp2396-427.
• 21. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr 2011;94(1):348-58. [CrossRef]
• 22. Glader B. Anemias of Inadequate Production. In: Kliegman RM, Behrman HR, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics, 18th ed. Philadelphia: Saunders; 2007.pp2006-18.
• 23. Stanger O, Weger M, Renner W, Konetschny R. Vascular dysfunction in hyperhomocyst(e)inemia. Implications for atherothrombotic disease. Clin Chem Lab Med 2001;39(8):725-33. [CrossRef]
• 24. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31-62. [CrossRef]
• 25. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64(3):169-72. [CrossRef]
• 26. Friedman G, Goldschmidt N, Friedlander Y, Ben-Yehuda A, Selhub J, Babaey S, et al. A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J Nutr 1999;129(9):1656-61. [CrossRef]
• 27. Lievers KJ, Boers GH, Verhoef P, den Heijer M, Kluijtmans LA, van der Put NM, et al. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl) 2001;79(9):522- 8. [CrossRef]
• 28. Carmeliet P, Collen D. Vascular development and disorders: molecular analysis and pathogenic insights. Kidney Int 1998;53(6):1519-49. [CrossRef]
• 29. Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol 2004;15(8):1983-92. [CrossRef]
• 30. McCully KS. Vascular pathology of homocysteinemia; implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56:111-28.
• 31. Coppo R, D’Amico G. Factors predicting progression of IgA nephropathies. J Nephrol 2005;18(5):503-12.
• 32. Aksu B, Emre S, Yılmaz A, Yürük ZN, Demirel ÜDM, Erol OB, et al. The relationship between serum asymmetric dimethylarginine levels and cardiovascular risk factors in children with nephrotic syndrome. Med Bull Haseki 2019;57:122-8. [CrossRef]
• 33. Kong X , Ma X, Zhang C, Su X, Xu D. Hyperhomocysteinemia increases the risk of chronic kidney disease in a Chinese middle-aged and elderly population-based cohort. Int Urol Nephrol 2017;49(4):661-7. [CrossRef]
• 34. Duan S, Liu S, Sun X, Zheng Y, Liu L, Yao F, et al. Potential association of hyperhomocysteinemia with the progression of IgA nephropathy: a retrospective study. Chin Med J 2014;127(10):1849-52.