Thrombotic microangiopathy after kidney transplantation: causes, clinical specifics and outcomes

Cover Page

Cite item

Abstract

Background: Thrombotic microangiopathy (TMA) is a clinical and morphological phenomenon characterized by specific microvascular injury, microangiopathic hemolytic anemia, and damage of various target organs. TMA after kidney transplantation (post-renal transplant TMA) is a serious complication affecting the recipient and graft survival.

Aim: To analyze the timing, causes, specifics of the clinical course and outcomes of TMA in renal transplant recipients.

Materials and methods: This one-center study was based on a comprehensive examination and follow-up of 697 patients who had undergone 728 kidney transplantations (KT) from deceased donors in 2003–2019. Post-transplant TMA of the renal graft was confirmed morphologically in all cases.

Results: We identified 32 episodes of post-transplant TMA in 32 patients; thus, the incidence of TMA was 4.4%. All cases developed after KT de novo; no recurrent TMA was observed. TMA was systemic in 37.5% and locally renal in 62.5% of the patients. The median time to the development of post-transplant TMA was 0.55 (range, 0.1 to 51.6) months. The patients with TMA did not differ from those without by gender, age, body mass index, underlying disorders, type and duration of dialysis before KT, protocols of immunosuppressive therapy, incidence of surgical, urological, infectious, cardiovascular and oncological complications. The patients with TMA were significantly more likely to have graft rejection (25.0% vs 11.2%, p = 0.035) and a never-functioning transplant (28.1% vs 4.9%, p < 0.001). The presence of TMA negatively affected the transplantation outcomes. The cumulative 1-year graft survival in the patients without and with TMA was 91% and 44%, respectively, whereas their 5-year survival rates were 68% and 25% (p < 0.001). The leading causes of TMA were: donor pathology (31.2%), antibody-mediated rejection (28.1%), and cyclosporine/tacrolimus nephrotoxicity (21.9%); the proportion of other causes was 18.8%. A combination of TMA etiological factors was identified in 68.7% of the recipients. The recipients with of calcineurin inhibitors nephrotoxicity had a more favorable prognosis compared to those with other causes of TMA.

Conclusion: Post-renal transplant TMA is an infrequent but serious complication that worsens the graft survival and often is life-threatening for recipients. In most cases, TMA develops in the early post-operative period; however, it can occur any time thereafter. To improve the outcome of TMA, early diagnosis is necessary based on clinical suspicion and a prompt biopsy of the renal graft with suspected TMA. Treatment should be started quickly with consideration of the cause of the complication.

About the authors

E. I. Prokopenko

Moscow Regional Research and Clinical Institute (MONIKI)

Author for correspondence.
Email: renalnephron@gmail.com
ORCID iD: 0000-0002-7686-9816

Elena I. Prokopenko – MD, PhD, Professor, Chair of Transplantology, Nephrology and Artificial Organs, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

Tel.: +7 (495) 684 57 91

Russian Federation

E. O. Shcherbakova

Moscow Regional Research and Clinical Institute (MONIKI)

Email: fake@neicon.ru
ORCID iD: 0000-0003-3817-6477

Evgeniya O. Shcherbakova – MD, PhD, Assistant, Chair of Transplantology, Nephrology and Artificial Organs, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

R. O. Kantaria

Moscow Regional Research and Clinical Institute (MONIKI)

Email: fake@neicon.ru
ORCID iD: 0000-0003-4388-7759

Rusudana O. Kantaria – MD, PhD, Associate Professor, Chair of Transplantology, Nephrology and Artificial Organs, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

V. A. Stepanov

Moscow Regional Research and Clinical Institute (MONIKI)

Email: fake@neicon.ru
ORCID iD: 0000-0002-0881-0599

Vadim A. Stepanov – MD, PhD, Senior Research Fellow, Surgical Department of Kidney Transplantation

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

References

  1. Bommer M, Wölfle-Guter M, Bohl S, Kuchenbauer F. The Differential Diagnosis and Treatment of Thrombotic Microangiopathies. Dtsch Arztebl Int. 2018;115(19): 327–34. doi: 10.3238/arztebl.2018.0327.
  2. Козловская НЛ, Демьянова КА, Кузнецов ДВ, Кучиева АМ, Боброва ЛА, Столяревич ЕС. «Субклиническая» тромботическая микроангиопатия при атипичном гемолитико-уремическом синдроме: единичный случай или закономерность? Нефрология и диализ. 2014;16(2): 280–7.
  3. de Azevedo FVA, Maia DG, de Carvalho JF, Rodrigues CEM. Renal involvement in antiphospholipid syndrome. Rheumatol Int. 2018;38(10): 1777–89. doi: 10.1007/s00296-018-4040-2.
  4. Garg N, Rennke HG, Pavlakis M, Zandi-Nejad K. De novo thrombotic microangiopathy after kidney transplantation. Transplant Rev (Orlando). 2018;32(1): 58–68. doi: 10.1016/j.trre.2017.10.001.
  5. Epperla N, Hemauer K, Hamadani M, Friedman KD, Kreuziger LB. Impact of treatment and outcomes for patients with posttransplant drug-associated thrombotic microangiopathy. Transfusion. 2017;57(11): 2775–81. doi: 10.1111/trf.14263.
  6. Caires RA, Marques ID, Repizo LP, Sato VA, Carmo LP, Machado DJ, de Paula FJ, Nahas WC, David-Neto E. De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival. Transplant Proc. 2012;44(8): 2388–90. doi: 10.1016/j.transproceed.2012.07.039.
  7. Reynolds JC, Agodoa LY, Yuan CM, Abbott KC. Thrombotic microangiopathy after renal transplantation in the United States. Am J Kidney Dis. 2003;42(5): 1058–68. doi: 10.1016/j.ajkd.2003.07.008.
  8. Teixeira CM, Tedesco Silva Junior H, Moura LAR, Proença HMS, de Marco R, Gerbase de Lima M, Cristelli MP, Viana LA, Felipe CR, Medina Pestana JO. Clinical and pathological features of thrombotic microangiopathy influencing longterm kidney transplant outcomes. PLoS One. 2020;15(1):e0227445. doi: 10.1371/journal.pone.0227445.
  9. Satoskar AA, Pelletier R, Adams P, Nadasdy GM, Brodsky S, Pesavento T, Henry M, Nadasdy T. De novo thrombotic microangiopathy in renal allograft biopsies – role of antibody-mediated rejection. Am J Transplant. 2010;10(8): 1804–11. doi: 10.1111/j.1600-6143.2010.03178.x.
  10. Rafat C, Coppo P, Fakhouri F, Frémeaux-Bacchi V, Loirat C, Zuber J, Rondeau E. [Hemolytic and Uremic Syndrome and Related Thrombotic Microangiopathies: Treatment and Prognosis]. Rev Med Interne. 2017;38(12): 833–9. doi: 10.1016/j.revmed.2017.07.005. French.
  11. Abbas F, El Kossi M, Kim JJ, Sharma A, Halawa A. Thrombotic microangiopathy after renal transplantation: Current insights in de novo and recurrent disease. World J Transplant. 2018;8(5): 122¬–41. doi: 10.5500/wjt.v8.i5.122.
  12. Broecker V, Bardsley V, Torpey N, Perera R, Montero R, Dorling A, Bentall A, Neil D, Willicombe M, Berry M, Roufosse C. Clinical-pathological correlations in post-transplant thrombotic microangiopathy. Histopathology. 2019;75(1): 88–103. doi: 10.1111/his.13855.
  13. Burton SA, Amir N, Asbury A, Lange A, Hardinger KL. Treatment of antibody-mediated rejection in renal transplant patients: a clinical practice survey. Clin Transplant. 2015;29(2): 118–23. doi: 10.1111/ctr.12491.
  14. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014;164(6): 759–66. doi: 10.1111/bjh.12718.
  15. Gonzalez Suarez ML, Thongprayoon C, Mao MA, Leeaphorn N, Bathini T, Cheungpasitporn W. Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis. J Clin Med. 2019;8(7): 919. doi: 10.3390/jcm8070919.
  16. Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodríguez de Córdoba S, Roumenina LT, Sethi S, Smith RJ; Conference Participants. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3): 539–51. doi: 10.1016/j.kint.2016.10.005.
  17. Satoh S, Saito K, Harada H, Okumi M, Saito M; Survey Committee for TA-TMA of the Japan Society for Transplantation. Survey of thrombotic microangiopathy within 1 week after kidney transplantation between 2010 and 2015 in Japan. Clin Exp Nephrol. 2019;23(4): 571–2. doi: 10.1007/s10157-018-1655-2.
  18. Vo AA, Sinha A, Haas M, Choi J, Mirocha J, Kahwaji J, Peng A, Villicana R, Jordan SC. Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization. Transplantation. 2015;99(7): 1423–30. doi: 10.1097/TP.0000000000000525.
  19. Saikumar Doradla LP, Lal H, Kaul A, Bhaduaria D, Jain M, Prasad N, Thammishetti V, Gupta A, Patel M, Sharma RK. Clinical profile and outcomes of De novo posttransplant thrombotic microangiopathy. Saudi J Kidney Dis Transpl. 2020;31(1): 160–8. doi: 10.4103/1319-2442.279936.
  20. De Keyzer K, Van Laecke S, Peeters P, Vanholder R. De novo thrombotic microangiopathy induced by cytomegalovirus infection leading to renal allograft loss. Am J Nephrol. 2010;32(5): 491–6. doi: 10.1159/000321328.
  21. Vilayur E, de Malmanche J, Trevillian P, Ferreira D. Metastatic lung adenocarcinoma-associated thrombotic microangiopathy in a renal transplant recipient. BMJ Case Rep. 2018;11(1):e226707. doi: 10.1136/bcr-2018-226707.
  22. Timmermans SAMEG, Abdul-Hamid MA, Potjewijd J, Theunissen ROMFIH, Damoiseaux JGMC, Reutelingsperger CP, van Paassen P; Limburg Renal Registry. C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe Hypertension. J Am Soc Nephrol. 2018;29(8): 2234–43. doi: 10.1681/ASN.2018020184.
  23. De Paolis P, Colonnelli R, Favarò A, Salem F, Vignally P, Carriero C, Iappelli M, Di Giulio S. Expanded Criteria Donor Kidney Transplantation: Comparative Outcome Evaluation Between Single Versus Double Kidney Transplantation at 8 Years: A Single Center Experience. Transplant Proc. 2016;48(2): 329–32. doi: 10.1016/j.transproceed.2016.02.007.
  24. Wang CJ, Wetmore JB, Crary GS, Kasiske BL. The Donor Kidney Biopsy and Its Implications in Predicting Graft Outcomes: A Systematic Review. Am J Transplant. 2015;15(7): 1903–14. doi: 10.1111/ajt.13213.
  25. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2): 388–99. doi: 10.1111/j.1600-6143.2011.03840.x.
  26. Столяревич ЕС, Жилинская ТР, Артюхина ЛЮ, Ким ИГ, Зайденов ВА, Томилина НА. Морфологическая структура патологии почечного аллотрансплантата и ее влияние на отдаленный прогноз. Вестник трансплантологии и искусственных органов. 2018;20(1): 45–54. doi: 10.15825/1995-1191-2018-1-45-54.
  27. Timmermans SAMEG, Abdul-Hamid MA, Vanderlocht J, Damoiseaux JGMC, Reutelingsperger CP, van Paassen P; Limburg Renal Registry. Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities. Kidney Int. 2017;91(6): 1420–5. doi: 10.1016/j.kint.2016.12.009.

Supplementary files

There are no supplementary files to display.


Copyright (c) 2020 Prokopenko E.I., Shcherbakova E.O., Kantaria R.O., Stepanov V.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies