Nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson’s disease

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Wilson’s disease is an inherited autosomal recessive disorder of copper balance leading to accumulation of copper mainly in liver and brain result from absent or reduced function of copper-transporting P-type ATPase. Copper is an essential trace element but in Wilson’s disease it accumulate to the point of toxicity. D-penicillamine is a classic drug for treatment of Wilson’s disease. Its major effect is to promote the urinary copper excretion. The use of D-penicillamine in the therapy of Wilson’s disease is known to be complicated by the development of various glomerular diseases. In this report we describe the development of nephrotic syndrome after 2 years treatment with D-penicillamine in a 31-year-old male undergoing treatment for Wilson’s disease, with a prompt regression at the discontinuation of the drug. We present this case to draw attention to the rare complication as nephrotic syndrome in patients with Wilson’s disease under D-penicillamine treatment and possible underlying causes. It is strongly necessary the therapy and clinical condition of patients with Wilson’s disease to be monitoring regularly - we recommended monthly.

1. European Association for the Study of the Liver: EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56:671-85.

2. Delangle P, Mintz E.Chelation therapy in Wilson’s disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators. DaltonTrans. 2012;41(21):6359-70. doi: 10.1039/c2dt12188c

3. Sözeri E, Feist D, Ruder H, Schärer K. Proteinuria and other renal functions in Wilson’s disease. Pediatr Nephrol. 1997;11(3):307-11. PMID:9203178

4. Mareček Z, Brůha R. Wilsons disease. Vnitr Lek. 2013; 59(7):578-83. PMID:23909262

5. Ranucci G, Di Dato F, Spagnuolo MI, Vajro P, Iorio R.Zinc monotherapy is effective in Wilson’s disease patients with mild liver disease diagnosed in childhood: a retrospective study. Orphanet J Rare Dis. 2014 Mar; 25:9(1):41. doi: 10.1186/1750-1172-9-41

6. Siafakas CG, Jonas MM, Alexander S, Herrin J, Furuta GT. Early onset of nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson’s disease. Am J Gastroenterol.1998 Dec; 93(12):2544-6.PMID:9860423

7. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML.Wilson’s disease. Lancet. 2007 Feb 3;369(9559):397-408. PMID:17276780

8. Khalil-Manesh F, Price RG. Effect of D-penicillamine on glomerular basement membrane, urinary N-acetyl- beta-D-glucosaminidase and protein excretion in rats. Toxicology. 1983;26(3-4):325-34.

9. Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther. 2009; 29(9):947-58. doi: 10.1111/j.1365-2036.2009.03959.x

10. Das SK, Ray K. Wilson’s Disease: An Update. Nat Clin Pract Neurol. 2006;2(9):482-493. PMID:16932613

11. Chang H, Xu A, Chen Z, Zhang Y, Tian F, Li T.Longterm effects of a combination of D-penicillamine and zinc salts in the treatment of Wilson’s disease in children. Exp Ther Med. 2013 Apr;5(4):1129-1132.PMID:23599735 [PubMed] PMCID:PMC3628594

12. Grasedyck K. D-penicillamine-side effects, pathogenesis and decreasing the risks. Z Rheumatol. 1988; 47(1):17-9. PMID:3063003

13. Huster D. Wilson disease. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):531-9. doi: 10.1016/j. bpg.2010.07.014

14. Rodríguez B, Burguera J, Berenguer M.Response to different therapeutic approaches in Wilson disease. A long-termfollow up study.Ann Hepatol. 2012 Nov-Dec; 11(6):907-14. PMID: 23109455

15. Ping CC, Hassan Y, Aziz NA, Ghazali R, Awaisu A.Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson’s disease. J Clin Pharm Ther. 2007 Feb;32(1):101-7. PMID: 17286794

16. Dong QY, Wu ZY. Advance in the pathogenesis and treatment of Wilson disease. Transl Neurodegener. 2012 Nov;1(1):23. doi: 10.1186/2047-9158-1-23

17. Lowette KF, Desmet K, Witters P, Laleman W, Verslype C, Nevens F, et al. Wilson’s disease: long-term follow-up of a cohort of 24 patients treated with D-penicillamine.Eur J Gastroenterol Hepatol. 2010 May;22(5):564-71. doi: 10.1097/MEG.0b013e3283353df8

18. 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(8):1028-35. e1-2. doi: 10.1016/j.cgh.2013.03.012

19. Członkowska A, Litwin T, Karliński M, Dziezyc K, Chabik G, Czerska M. D-penicillamine versus zinc sulfate as first-line therapy for Wilson’s disease. Eur J Neurol. 2014 Apr;21(4):599-606. doi: 10.1111/ ene.12348

20. Sternlieb I, Scheinberg H. Prevention of Wilson’s Disease in Asymptomatic Patients. N Engl J Med. 1968;278:352-9. PMID: 5635646

21. Habib GS, Saliba W, Nashashibi M, Armali Z. Penicillamine and nephrotic syndrome. Eur J Intern Med. 2006 Aug;17(5):343-8. PMID: 16864010

22. Scheinberg IH, Sternlieb I. Wilson disease. in Major problems in internal medicine. eds Lloyd H, Smith J (Saunders, Philadelphia), 1984; 134-49

23. Adams DA, Goldman R, Maxwell MH, Latta H. Nephrotic Syndrome Associated with Penicillamine Therapy of Wilson’s Disease. Am J Med. 1964 Feb;36:330-6. PMID: 14124700

24. Tesar V, Zima T, Kalousová M. Pathobiochemistry of nephrotic syndrome. Adv Clin Chem. 2003;37:173-218. PMID: 12619708

25. Ozçakar Z, Ekim M, Ensari A, Kuloglu Z, Yüksel S, Acar B, et al. Membranoproliferative glomerulonephritis in a patient with Wilson’s disease. J Nephrol. 2006;19(6):831-3. PMID: 17173260

26. Koraishy FM, Cohen RA, Israel GM, Dahl NK. Cystic Kidney Disease in a Patient With Systemic Toxicity From Long-term d-Penicillamine Use. Am J Kidney Diseases. 2013 Oct; 62(4): 806-809. doi: 10.1053/j. ajkd.2013.04.017

27. Davis P, Bleehen SS. D-penicillamine in the treatment of rheumatoid arthritis and progressive systemic sclerosis. Br J Dermatol. 1976 Jun;94(6):705-11. PMID:779821

28. Dzieżyc K, Karliński M, Litwin T, Członkowska A. Compliant treatment with anti-copper agents prevents clinically overt Wilson’sdisease in pre-symptomatic patients. Eur J Neurol. 2014 Feb;21(2):332-7. doi: 10.1111/ene.12320

29. Sanches MR. Miscellaneous Treatments: Thalidomide, Potassium Iodide, Levamisole, Clofazimine, Colchicine, and D-Penicillamine. Clin Dermatol. 2000;18:131-45. PMID: 10701095

30. Walshe JM. Monitoring copper in Wilson’s disease. Adv Clin Chem. 2010;50:151-63. PMID: 20521445

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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