Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Is routine screening examination necessary for detecting thromboembolism in childhood nephrotic syndrome?

소아 신증후군 환자에서 혈전증 검색을 위해screening 검사가 필요한가?

  • Kim, Mun Sub (Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine) ;
  • Koo, Ja Wook (Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine) ;
  • Kim, Soung Hee (Departments of Radiology, Sanggye Paik Hospital, Inje University College of Medicine)
  • 김문섭 (인제대학교 의과대학 상계백병원 소아청소년과) ;
  • 구자욱 (인제대학교 의과대학 상계백병원 소아청소년과) ;
  • 김성희 (인제대학교 의과대학 상계백병원 영상의학과)
  • Received : 2007.12.02
  • Accepted : 2008.04.04
  • Published : 2008.07.15
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Abstract

Purpose : The incidence of thromboembolic episodes in children with nephrotic syndrome (NS) is low; however, these episodes are often severe. Moreover, both pulmonary thromboembolism (PTE) and renal vein thrombosis (RVT) rarely show clinical symptoms. This study was performed to determine the benefits of routine screening in the detection of thrombosis in childhood NS. Methods : Among 62 children with nephrotic syndrome, a total of 54 children (43 males, 11 females) were included in this study. When the patients experienced their first NS episode, we performed renal Doppler ultrasonography in order to detect RVT. To rule out the possibility of PTE, a lung perfusion scan was performed. Computed tomographic (CT) pulmonary angiography was recommended to patients who showed possible signs of PTE. All patients were evaluated for clinical signs of thrombosis, biochemical indicators of renal disease, as well as clotting and thrombotic parameters. Results : RVT or related clinical symptoms were not observed in any children. Based on the findings of the lung perfusion scans, 15 patients (27.8%) were observed with as a high probability of PTE. We were able to perform a CT pulmonary angiography only on 12 patients, and 5 patients were diagnosed with PTE (prevalence 8.1%). The serum fibrinogen level in the group with PTE was significantly higher ($776.7{\pm}382.4mg/dL$, P<0.05) than that in the group without PTE, and other parameters were not significantly different between each group. Conclusion : Further studies are required for clarifying the role of renal Doppler ultrasonography for the detection of RVT in NS. Children with NS who developed non-specific respiratory symptoms should be evaluated for the diagnosis of PTE. In the management of NS, a lung perfusion scan should be performed at the time of the initial episode of NS regardless of the pulmonary symptoms, since patients having PTE are either often asymptomatic, or present with nonspecific symptoms.

목 적 : 소아 신증후군에서 혈전-색전증은 낮은 빈도이지만 심각한 임상 경과를 취하는 합병증이다. 그러나 폐 혈전-색전증의 경우 실제 임상에서 호흡 곤란, 빈호흡, 흉막 동통, 각혈 및 청진상 수포음 또는 호흡음 감소 등의 뚜렷한 임상 증세를 보이는 경우는 드물고, 신정맥 혈전증의 경우도 요통, 육안적 혈뇨 및 신비대 등의 전형적인 소견을 보이는 경우는 드물다. 이에 저자들은 처음 신증후군으로 진단된 환아에서 혈전-색전증 확인을 위한 screening 검사가 필요한지 알기 위해 본 연구를 시행하였다. 방 법 : 신증후군을 진단 받은 62명의 환아 중 폐 관류 검사와 신장 도플러 초음파 검사를 실시한 54명을 연구에 포함하였다. 신장 초음파 검사와 폐 관류 검사는 처음 신증후군 진단 후 2주 이내에 실시하였고, 폐 관류 검사가 양성일 경우 컴퓨터 단층 폐 혈관 조영 검사를 실시하여 이상이 있을 경우에만 폐 혈전-색전증으로 진단하였다. 또한 모든 환아들은 혈전-색전증의 임상적 징후와 신장 질환의 생화학적 지표, 혈액 응고 지표를 측정하였다. 결 과 : 검사 기간 동안 임상 증세 및 신장 초음파 검사상 신정맥 혈전증을 보인 환아는 없었다. 폐 관류 스캔상 이상 소견을 보여 폐 혈전색전증이 의심된 경우는 15례(27.8%)였으나, 이 중 12명만 컴퓨터 단층 폐 혈관 조영 검사가 가능하여 폐 혈전-색전증으로 확진된 경우는 모두 5례로, 폐 혈전-색전증의 발생 빈도는 8.1%였다. 폐 혈전-색전증 5례 중 3례에서만 기침, 가래, 빈호흡, 청진상 수포음, 호흡음 감소 등의 비특이적인 호흡기 증세를 나타내었으며, 2례는 청진 소견상 정상이었다. 또한 폐 혈전-색전증이 없었던 49명의 환아 중 21명이 비특이적 호흡기 증상을 나타내어 두 그룹 간에 호흡기 증상의 발생률의 차이는 없었다. 신장 질환의 생화학적 지표와 혈액 응고 지표 중 폐 혈전-색전증 그룹의 평균 섬유소원 농도만 $776.7{\pm}382.4mg/dL$로 유의하게 높았다(P<0.05). 결 론 : 신증후군 환아에서 신정맥 혈전증 진단을 위한 신장 도플러 초음파 검사의 역할은 분명치 않아 향후 더 많은 연구가 필요할 것으로 생각된다. 신증후군 환아에서 비특이적인 흉부 증상, 청진상 호흡음의 감소가 있을 경우 반드시 폐 혈전-색전증의 유무를 확인하여야 한다. 그러나 폐 혈전-색전증으로 확진된 경우에도 호흡기 증상 및 징후가 없는 경우가 있어서 폐 혈전-색전증을 임상적으로 진단하기가 쉽지 않다. 따라서, 초기 발병 후 완해가 오기 전 신증후군 재발을 많이 하는 시기에는 무증상의 신증후군 환아도 폐 혈전-색전증의 가능성을 염두에 두고 폐 관류 스캔을 screening 검사로 시행하여야 할 것으로 사료된다.

Keywords

References

  1. Mehls O, Andrassy K, Koderisch J. Herzog D, Ritz E. Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults. J Pediatr 1987;110:862-7 https://doi.org/10.1016/S0022-3476(87)80397-9
  2. Egli F, Elminger P, Stalder G. Thromboembolism in nephrotic syndrome. abstract 42 Eur Soc Pediatr Nephrol, Pediatrics 1974;8:903
  3. Nowak-Gottl D, Kosch A, Schlegel N. Neonatal thromboembolism. Semin Thromb Hemost 2003;29:227-34 https://doi.org/10.1055/s-2003-38839
  4. Robert A, Olmer M, Sampol J, Gugliotta J, Casanova P. Clinical correlation between hypercoagulabilitv and thrombo-embolic phenomena, Kidney Int 1987;31:830-5 https://doi.org/10.1038/ki.1987.73
  5. Machleidt C, Mettang T, Starz E, Weber J, Risler T, Kuhlmann U. Multifactorial genesis of enhanced platelet aggregability in patients with nephrotic syndrome. Kidney Int 1989; 36:1119-24 https://doi.org/10.1038/ki.1989.310
  6. Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome, Kidney Int 1985;28:429- 39 https://doi.org/10.1038/ki.1985.149
  7. Orth SR, Ritz E, The nephrotic syndrome. N Engl J Med 1998;338:1202-11 https://doi.org/10.1056/NEJM199804233381707
  8. Lilova MI, Velkovski IG, Topalov ill, Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974-1996), Pediatr Nephrol 2000;15:74-8 https://doi.org/10.1007/s004679900253
  9. van Ommen CH, Heyboer H, Groothoff JW, Teeuw R, Aronson DC, Peter M. Persistent tachypnoea in children: keep pulmonary embolism in mind. J Pediatr Hematol Oncol 1998;20:570-3 https://doi.org/10.1097/00043426-199811000-00016
  10. Deshpande PV, Griffiths M. Pulmonary thrombosis in steroid-sensitive nephrotic syndrome, Pediatr Nephrol 2005;20: 665-9 https://doi.org/10.1007/s00467-004-1741-4
  11. Stein PO, Willis PW 3rd, DeMets DL. History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease, Am J Cardiol 1981;47:218-23 https://doi.org/10.1016/0002-9149(81)90388-X
  12. Llach F, Papper S. The clinical spectrum of renal vein thrombosis: acute and chronic, Am J Med 1980;69:819-27 https://doi.org/10.1016/S0002-9343(80)80006-4
  13. Stein PO, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism, N Engl J Med 2006:354:2317-27 https://doi.org/10.1056/NEJMoa052367
  14. Stein PO, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators, Am J Med 2006:119:1048-55 https://doi.org/10.1016/j.amjmed.2006.05.060
  15. Vest EA, Avner ED, Nephrotic syndrome. In : Behrman HE, Kliegrnan RM, Jenson HE, editors, Nelson Textbook of Pediatrics, 17th ed. Philadelphia : WB Saunders Co, 2004: 1754-7
  16. Chesney RW, The idiopathic nephrotic syndrome. Curr Opin Pediatr 1999; 11:158-61 https://doi.org/10.1097/00008480-199904000-00010
  17. Bagga A, Mantan M, Nephrotic syndrome in children. J Indian J Med Res 122 2005;13-28
  18. Churg J. Habib R, White RH, Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet 1970 20;760:1299-302
  19. Moorani KN, Khan KM, Ramzan A Infections in children with nephrotic syndrome, J Coli Physicians Surg Pak. 2003; 13:337-9
  20. Wu HM, Tang JL, Sha ZB, Cao L, Li YP. Interventions for preventing infection in nephrotic syndrome. Cochrane Database Syst Rev. 2004
  21. Eddy AA, Symons JM. Nephrotic syndrome in childhood, Lancet 2003 23;362:629-39
  22. Constantinescu AR, Shah HE, Foote EF, Weiss LS, Predicting first-year relapses in children with nephrotic syndrome. Pediatrics 2000; 105:492-5 https://doi.org/10.1542/peds.105.3.492
  23. Ginsberg JS, 'Management of venous thromboembolism. N Engl J Med 1996:335:1816-28 https://doi.org/10.1056/NEJM199612123352407
  24. Kaysen GA. Nonrenal complications of the nephritic syndrome. Annu Rev Med 1994;45:201-10 https://doi.org/10.1146/annurev.med.45.1.201
  25. Cameron JS. Coagulation and thromboembolic complications in the nephrotic syndrome. Adv Nephrol 1984;13:75-114
  26. Llach F, Koffler A, Massay SG. "Renal vein thrombosis and the nephrotic syndrome. Nephron 1977:19:65-8 https://doi.org/10.1159/000180867
  27. Hoyer PF, Gonda S, Barthels M, Krohn HP, Brodehl J. Thromboembolic complications in children with nephrotic syndrome risk and incidence. Acta Paediatr Scand 1986;75: 804-10 https://doi.org/10.1111/j.1651-2227.1986.tb10294.x
  28. Mehls O, Andrassy K, Ritz E. Disseminated intravascular coagulation and platelet activation in nephrotic syndrome. Eur J Paediatr 1984;141:261-6
  29. Kanfer A, Kleinknecht D, Broyer M, Iosso F. Coagulation studies in 45 cases of nephrotic syndrome without uremia. Thromb Diath Haemorrh 1970:31:24:562-71
  30. Zwaginaa JJ, Koornans HA, Sixma JJ. Habelink TJ. Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest 1994;93:204-11 https://doi.org/10.1172/JCI116947
  31. Andrassy K, Ritz E, Bommer J. Hypercoagulability in the Nephrotic syndrome. Klin Wochenschr 1980;58:1029-36 https://doi.org/10.1007/BF01476873
  32. Bellomo R, Atkins HC. Membranous nephropathy and thromboembolism: is prophylactic anticoagulation warranted? Nephron 1993;63:249-54 https://doi.org/10.1159/000187205
  33. Kanfer A. Coagulation factors in nephritic syndrome. Am J Nephrol 1990;10:63-8 https://doi.org/10.1159/000168196
  34. Hathaway WE. Use of antiplatelet agents in pediatric hypercoagulable states. Am J Dis Child 1984:138:301-4
  35. Hodson E. The management of idiopathic nephrotic syndrome in children. Paediatr Drugs 2003;5:335-49 https://doi.org/10.2165/00128072-200305050-00006
  36. Alkjaersig N, Fletcher AP, Narayanan M, Robson AM. Course and resolution of the coagulopathy in nephrotic children. Kidney Int 1987;31:772-80 https://doi.org/10.1038/ki.1987.65
  37. Lieberman E, Heuser E, Gilchrist GS, Donnell GN, Landing BH Thrombosis, nephrosis and corticosteroid therapy, J Pediatr 1968;73:320-8 https://doi.org/10.1016/S0022-3476(68)80107-6
  38. Ueda N, Effect of corticosteroids on some hemostatic parameters in children with minimal change nephrotic syndrome. Nephron 1990;56:374-8 https://doi.org/10.1159/000186178
  39. Andrew M, Brooker LA. Hemostatic complications in renal disorders of the young. Pediatr Nephrol 1996;10:88-99 https://doi.org/10.1007/BF00863459
  40. Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Thrornb Res 2006;118:397-407 https://doi.org/10.1016/j.thromres.2005.03.030
  41. Zaffanello M, Franchini M. Thromboembolism in childhood nephrotic syndrome: A rare but serious complication. Hematology 2007;J2:69-73
  42. Hull RD, Hirsh J, Carter CJ, Jay RM, Dodd PE, Ockelford P, et al. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan. Ann Intern Med 1983;98:891-9 https://doi.org/10.7326/0003-4819-98-6-891
  43. Bell WR, Simon TL, DeMets DL. The clinical features of submassive and massive pulmonary emboli. Am J Med 1977;62:355-60 https://doi.org/10.1016/0002-9343(77)90832-4
  44. Cherng SC, Huang WS, Wang YF, Yang SP, Lin YF. The role of lung scintigraphy in the diagnosis of nephrotic syndrome with pulmonary embolism. Clin Nucl Med 2000;25: 167-72 https://doi.org/10.1097/00003072-200003000-00001
  45. Mitral BR, Singh S, Bhattacharya A, Prasada V, Singh B, Lung scintigraphy in the diagnosis and follow-up of pulmonary thromboembolism in children with nephrotic syndrome. J Clinl Imaging 2005;29:313-6 https://doi.org/10.1016/j.clinimag.2005.01.026
  46. Koo JW, Park HW, Ha TS, Ha IS, Cheong HI, Choi Y. Thromboembolic complication in children with nephritic syndrome. Korean J Nephrol 1993;12:579-87