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

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Abstract

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.

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Abbreviations

aHUS:

Atypical haemolytic uremic syndrome

AMR:

Antibody-mediated rejection

ATG:

Anti-thymocyte globulin

CFH:

Complement factor H

CFI:

Complement factor I

CMV:

Cytomegalovirus

CNI:

Calcineurin inhibitor

DSA:

Donor-specific antibodies

EBV:

Epstein–Barr virus

HUS:

Haemolytic uremic syndrome

ICAM:

Intercellular adhesion molecule

IL:

Interleukin

LDH:

Lactate dehydrogenase

MMF:

Mycophenolate mofetil

MPGN:

Membranoproliferative glomerulonephritis

m-TOR:

Mammalian target of rapamycin

PAS:

Periodic acid-Schiff stain

PD:

Peritoneal dialysis

PE:

Plasma exchange

PRA:

Panel reactive antibodies

SFOG:

Acid fuchsin orange G stain

TMA:

Thrombotic microangiopathy

TCC:

Terminal complement complex

TTP:

Thrombotic thrombocytopenic purpura

USRDS:

United States Renal Data System

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Acknowledgements

The work of J.H. is supported by the Tiroler Wissenschaftsfond and the Österreichische Nationalbank (grant: 12711)

Conflict of interest

J.H. has received an honorarium from Alexion Pharmaceuticals Inc and has served on various advisory boards.

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Authors and Affiliations

  1. Department of Paediatrics I, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Gerard Cortina, Raphaela Trojer, Siegfried Waldegger & Johannes Hofer

  2. Department of Visceral and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria

    Stefan Schneeberger

  3. Department of Pathology, Innsbruck Medical University, Innsbruck, Austria

    Nadezda Gut

Authors
  1. Gerard Cortina
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  2. Raphaela Trojer
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  3. Siegfried Waldegger
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  4. Stefan Schneeberger
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  5. Nadezda Gut
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  6. Johannes Hofer
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Corresponding author

Correspondence to Johannes Hofer.

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Cortina, G., Trojer, R., Waldegger, S. et al. De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus. Pediatr Nephrol 30, 693–697 (2015). https://doi.org/10.1007/s00467-014-3036-8

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  • DOI: https://doi.org/10.1007/s00467-014-3036-8

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