Wilson Hastalıklı Çocuklarda Böbrek Fonksiyonlarının Değerlendirilmesi

Yıl 2017, , 6 - 11, 01.04.2017

Yılmaz Tabel , Mukadder Ayşe Selimoğlu Fatma İlknur Varol Ahmet Taner Elmas Şükrü Güngör Hamza Karabiber

https://doi.org/10.4274/jcp.43760

Öz

Giriş: Bu çalışmada Wilson hastalığında WH böbrek fonksiyonlarının üriner N-Asetil-β-D-glukozaminidaz NAG ve NAG/kreatinin aktivite indeksi kullanılarak değerlendirilmesi amaçlanmıştır.Gereç ve Yöntem: WH tanısı alan 20 hasta çalışma grubu, benzer yaş ve cinsiyette olan 37 sağlıklı çocuk kontrol grubu olarak alındı. NAG düzeyleri mlU/L olarak hesaplanırken, NAG aktivite indeksi mlU/mg kreatinin olarak belirlendi.Bulgular: Toplam dört hasta %20 tanı anında asemptomatik iken; sırasıyla kronik hepatit, nörolojik WH, fulminan hepatit ve akut hepatit ise altı %30 , beş %25 , üç %15 ve iki %10 hastada saptandı. Çalışma anında toplam 13 hasta %65 trientin ve çinko tedavisi alırken, yedi %35 hasta ise D-penisilamin ve çinko tedavileri almaktaydı. Olguların 10’unda %50 proteinüri, birinde %5 glikozüri ve bir hastada %5 mikroskopik hematüri saptandı. Hasta grubunun idrar sodyumu ve kreatinini kontrol grubundan anlamlı olarak düşük iken p=0,048 ve p=0,001 , NAG ve NAG indeks anlamlı olarak daha yüksek saptandı p=0,049 ve p=0,03 . Klinik başvuru şeklinin bu parametreler üzerinde etkili olmadığı gözlendi p> 0,05 . İdrar kreatinini trientin alanlarda anlamlı olarak yüksek bulundu p=0,004 . Child-Pugh skoru ile bu parametreler arasında herhangi bir ilişki saptanmadı p> 0,05 . Sonuç: Bu çalışmada; WH’li çocuklarda WH’nin kendisinin ve/veya kullanılan ilaçların böbrek fonksiyonları üzerine olumsuz etkisinin olduğu, karaciğer hasarının ciddiyeti ve klinik özelliklerin etkisinin olmadığı görülmüştür

Anahtar Kelimeler

Çocuk, böbrek fonksiyonları, N-asetil-β-Dglikozaminidaz, Wilson hastalığı

Evaluation of Renal Function in Children with Wilson’s Disease

Öz

Introduction: In this study it was aimed to evaluate the renal functions in Wilson’s disease WD using urinary N-acetyl-β-D-glucosaminidase NAG and NAG/creatinine activity index.Materials and Methods: Twenty children of similar age and gender with WD were determined to be the patient group and 37 healthy children were determined to be the control group for the study. NAG levels were calculated as mlU/L and NAG activity index was determined as mlU/mg.Results: While four 20% patients were asymptomatic at diagnosis, chronic hepatitis, neurologic WD, fulminant hepatitis, and acute hepatitis were observed in six 30% , five 25% , three 15% , and two 10% patients, respectively. Of children, 13 65% were on trientine and zinc treatment and seven 35% were on d-penicillamine and zinc. Ten 50% children had proteinuria, one 5% had glycosuria, and one 5% had microscopic hematuria. While mean urine sodium and creatinine levels were significantly lower compared to controls p=0.048 and p=0.001, respectively , NAG and NAG index were significantly higher p=0.049 and p=0.03 . Clinical presentation was observed to be not effective on those parameters p> 0.05 . No relationship was found between Child-Pugh score and these parameters p> 0.05 . Conclusions: It was concluded that while WD itself and/or the drugs that are used for the treatment have negative effects on renal functions for children with WD, however it does not have any effect on the liver damage severity and clinical presentation of the disease.

Anahtar Kelimeler

Children, renal function, N-acetyl-β-Dglucosaminidase, Wilson’s disease

Kaynakça

• 1. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson’s disease. Lancet 2007;369:397-408.
• 2. Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC. Wilson’s disease: A review of what we have learned. World J Hepatol 2015;7:2859-70.
• 3. Sozeri E, Feist D, Ruder H, Scharer K. Proteinuria and other renal functions in Wilson’s disease. Pediatr Nephrol 1997;11:307-11.
• 4. Bearn AG, Yu TF, Gutman AB. Renal function in Wilson’s disease. J Clin Invest 1957;36:1107-14.
• 5. Leu ML, Strickland GT, Gutman RA. Renal function in Wilson’s disease. response to penicillamine therapy. Am J Med Sci 1970;260:381-98.
• 6. Peterson PA, Evrin PE, Berggard I. Differentiation of glomerular, tubular and normal proteinuria: determination of urinary excretion of b2-microglobulin, albumin, and total protein. J Clin Invest 1969;48:1189-98.
• 7. Csáthy L, Pocsi I. Urinary N-acetyl-â-D-glucosaminidase determination in newborns and children: methods and diagnostic applications. Eur J Clin Chem Clin Biochem 1995;33:575-87.
• 8. Price RG. Urinary enzymes, nephrotoxicity and renal disease. Toxicology 1982;23:98-134.
• 9. Kunin CM, Chesney RW, Craig WA, England AC, De Angelis C. Enzymuria as a marker of renal injury and disease: studies of N-acetyl-â-D-glucosaminidase in the general population and in patients with renal disease. Pediatrics 1978;64:751-60.
• 10. Watanabe K, Kojima K, Fukuda J, Ohbayasi K, Kobayashi T, Iwase S, et al. Reliability of urinary N-acetyl-â-D-glucosaminidase as an indicator of renal tubular damage in neonates. Biol Neonate 1987;52:16-21.
• 11. Kavukcu S, Spylu A, Turkmen M. The clinical value of urinary N-acetyl-beta-D glucosaminidase levels in childhood age group. Acta Med Okoyama 2002;56:7-11.
• 12. http://www.mdcalc.com/child-pugh-score-for-cirrhosis￾mortality/ last accessed: 26.02.2016
• 13. Schonheyder F, Gregersen G, Hansen HE, Skov PE. Renal clearances of different aminoacids in Wilson’s disease before and after treatment with penicillamine. Acta Med Scand 1971;190:395-9.
• 14. Hoppe B, Neuhaus T, Superti-Furga A, Forster I, Leumann E. Hypercalciuria and nephrocalcinosis, a feature of Wilson’s disease. Nephron 1993;65:460-2.
• 15. Tesar V, Mokrejsova M, Marecek Z, Petrtyl J. Distal renal tubular acidosis in patients with Wilson’s disease. Sb Lek 1991;93:315- 23.
• 16. Paklar AV, Shrivastava MS, Padwal NJ, Padhiyar RN, Moulick N. Renal tubular acidosis due to Wilson’s disease presenting as metabolic bone disease. BMJ Case Reports 2011.
• 17. Morgan HG, Stewart WK, Lome KG, Stowers JM, Johnstone JH. Wilson’s disease and the Fanconi syndrome. Q J Med 1962;31:361-84.
• 18. Gül A, Sütçüoğlu S, Akman SA, Bakiler AR, Taştan M, Özgenç F, et al. A rare clinical presentation in Wilson’s disease: renal involvement. Turkiye Klinikleri J Pediatr 2005;14:217-9.
• 19. Farallo M, Amoruso C, Frattini C, Ardissino G, Nebbia G. Nephrotic syndrome after treatment with d-penisilamin in a pediatric patient with Wilson’s disease. Pediatr Med Chir 2012;34:234-6.
• 20. Lee Y, Lee ST, Cho H. D-penisilamin-induced ANA (+) ANCA (+) vasculitis in pediatric patients with Wilson’s disease. Clin Nephrol 2016;19.
• 21. Hoppe B, Neuhaus T, Superti-Furga A, Forster I, Leumann E. Hypercalciuria and nephrocalcinosis, a feature of Wilson’s disease. Nephron 1993;65:460-2.
• 22. Zhuang XH, Mo Y, Jiang XY, Chen SM. Analysis of renal impairment in children with Wilson’s disease. World J Pediatr 2008;4:102-5.
• 23. Wu F, Wang J, Pu C, Qiao L, Jiang C. Wilson’s Disease: A comprehensive review of the molecular mechanisms. Int J Mol Sci 2015;16:6419-31.
• 24. Elsas LJ, Hayslett JP, Spargo BH, Durant JL, Rosenberg LE. Wilson’s disease with reversible renal tubular dysfunction. Correlation with proximal tubular ultrastructure. Ann Intern Med 1971;75:427-33.
• 25. Jaffe IA, Treiser G, Suzuki Y, Ehrenreich T. Nephropathy induced by d-penisilamin. Ann Intern Med 1968;69:549-55.
• 26. Hosovski E, Sunderic D, Sindjic M. Functional and histologic changes in the kidney in copper poisoning in rats (in Serbo￾Croatian). Srp Arh Celok Lek 1990;118:445-9.
• 27. Lau JYN, Lai CL, Wu PC, Pan HYM, Lin HJ, Todd D. Wilson’s disease: 35 years experience. QJM 1990;278:597-605.
• 28. Wang H, Zhou Z, Hu J, Han Y, Wang X, Cheng N, et al. Renal impairment in different phenotypes of Wilson disease. Neurol Sci 2015;36:2111-5.
• 29. Weiss KH, Thurik F, Gotthardt DN, Schäfer M, Teufel U, Wiegand F, et al; EUROWILSON Consortium. Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol 2013;11:1028-35.