De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus

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• 作者：Gerard Cortina (1)
  Raphaela Trojer (1)
  Siegfried Waldegger (1)
  Stefan Schneeberger (2)
  Nadezda Gut (3)
  Johannes Hofer (1)
  
  1. Department of Paediatrics I ; Innsbruck Medical University ; Anichstrasse 35 ; 6020 ; Innsbruck ; Austria
  2. Department of Visceral and Transplant Surgery ; Innsbruck Medical University ; Innsbruck ; Austria
  3. Department of Pathology ; Innsbruck Medical University ; Innsbruck ; Austria
  
• 关键词：De novo TMA ; Antibody ; mediated rejection ; CNI ; induced TMA ; Atypical HUS ; CFH polymorphisms
• 刊名：Pediatric Nephrology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：30
• 期：4
• 页码：693-697
• 全文大小：805 KB
• 参考文献：1. Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Fr茅meaux-Bacchi V (2013) Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 13(3):663鈥?75 CrossRef
  2. Satoskar AA, Pelletier R, Adams P, Nadasdy GM, Brodsky S, Pesavento T, Henry M, Nadasdy T (2010) De novo thrombotic microangiopathy in renal allograft biopsies-role of antibody-mediated rejection. Am J Transplant 10(8):1804鈥?811 CrossRef
  3. Caires RA, Marques ID, Repizo LP, Sato VA, Carmo LP, Machado DJ, de Paula FJ, Nahas WC, David-Neto E (2012) De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival. Transplant Proc 44(8):2388鈥?390 CrossRef
  4. Liptak P, Ivanyi B (2006) Primer: histopathology of calcineurin-inhibitor toxicity in renal allografts. Nat Clin Pract Nephrol 2(7):398鈥?04 CrossRef
  5. Meehan SM, Kremer J, Ali FN, Curley J, Marino S, Chang A, Kadambi PV (2011) Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies. Clin J Am Soc Nephrol 6(2):395鈥?03 CrossRef
  6. Riedl M, Fakhouri F, Le Quintrec M, Noone DG, Jungraithmayr TC, Fremeaux-Bacchi V, Licht C (2014) Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic insights identifying novel treatment approaches. Semin Thromb Hemost 40(4):444鈥?64 CrossRef
  7. Neumann HP, Salzmann M, Bohnert-Iwan B, Mannuelian T, Skerka C, Lenk D, Bender BU, Cybulla M, Riegler P, K枚nigsrainer A, Neyer U, Bock A, Widmer U, Male DA, Franke G, Zipfel PF (2003) Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries. J Med Genet 40:676鈥?81 CrossRef
  8. Abrera-Abeleda MA, Nishimura C, Smith JL, Sethi S, McRae JL, Murphy BF, Silvestri G, Skerka C, J贸zsi M, Zipfel PF, Hageman GS, Smith RJ (2006) Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J Med Genet 43:582鈥?89 CrossRef
  9. Reynolds JC, Agodoa LY, Yan CM, Abbott KC (2003) Thrombotic microangiopathy after renal transplantation in the United States. Am J Kidney Dis 42:1858 CrossRef
  10. Noris M, Remuzzi G (2010) Thrombotic microangiopathy after kidney transplantation. Am J Transplant 10:1517鈥?523 CrossRef
  11. Devadoss CW, Vijaya VM, Mahesh E, Venkataramana SR, Girish MS (2012) Tacrolimus associated localized thrombotic microangiopathy developing in early stage after renal transplantation. J Clin Diagn Res 6:1786鈥?788
  12. Schwimmer J, Nadasdy TA, Spitalnik PF, Kaplan KL, Zand MS (2003) De novo thrombotic microangiopathy in renal transplant recipients: a comparison of HUS with localized renal TMA. Am J Kidney Dis 41:471鈥?79 CrossRef
  13. Noone D, Al-Matrafi J, Tinckam K, Zipfel PF, Herzenberg AM, Thorner PS, Pluthero FG, Kahr WH, Filler G, Hebert D, Harvey E, Licht C (2012) Antibody mediated rejection associated with complement factor H-related protein 3/1 deficiency successfully treated with eculizumab. Am J Transplant 12(9):2546鈥?553 CrossRef
  14. Hofer J, Rosales A, Fischer C, Giner T (2014) Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr 97:2296鈥?360
  15. Keller K, Daniel C, Sch枚cklmann H, Endlich KH, Kerjaschki D, Johnson RJ, Hugo C (2006) Everolimus inhibits glomerular endothelial cell proliferation and VEGF, but not long-term recovery in experimental thrombotic microangiopathy. Nephrol Dial Transplant 21:2724鈥?735 CrossRef
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pediatrics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-198X

文摘

Background Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA) is a rare complication after renal transplantation. It may be difficult to distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its clinical presentation may vary from isolated localised forms up to catastrophic systemic presentations. Case We report a case of tacrolimus-induced TMA soon after renal transplantation in an 11-year-old boy who received his second renal transplantation. His first graft was lost because of AMR. On day 12 after his second renal transplantation, his renal function started worsening and a kidney biopsy was performed, which showed histopathological signs of TMA. The diagnosis of tacrolimus-induced TMA was established after excluding AMR and other causes of de novo TMA. Genetic complement investigation disclosed two complement factor H risk polymorphisms as possible modifiers of TMA emergence. Treatment was based on replacing tacrolimus with everolimus, with a subsequent normalisation of renal function. Conclusion A prompt diagnosis of de novo TMA by early allograft biopsy is essential for the allograft outcome and genetic investigations for possible complement abnormalities are reasonable, not only for patients with a systemic aspect of their post-transplant TMA. Replacing tacrolimus with everolimus effectively controlled the TMA and stabilised renal function in our patient.