Clinical–pathological correlations in post-transplant thrombotic microangiopathy

Verena Broecker, Victoria Bardsley, Nicholas Torpey, Ranmith Perera, Rosa Montero, Anthony Dorling, Andrew Bentall, Desley Neil, Michelle Willicombe, Miriam Berry, Candice Roufosse

Research output: Contribution to journalArticle

Abstract

Aims: Post-transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uraemic syndrome, TMA in renal transplants is associated with various conditions, such as calcineurin inhibitor (CNI) treatment, antibody-mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies, and surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post-transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multicentre retrospective study. Methods and results: Clinical parameters and transplant renal biopsy findings from 81 patients with TMA were analysed. Biopsies from 38 patients were also analysed with electron microscopy. On the basis of clinical–pathological correlation, TMA was attributed to a main aetiology, whenever possible. TMA occurred at a median of 30 days post-transplantation. Systemic features of TMA were present in only 18% of cases. Twenty-two per cent of cases were attributed to CNI and 11% to ABMR. Although other potentially contributing factors were found in 56% of patients, in most cases (63%) no clearly attributable cause of TMA was identified. Histological differences between groups were minimal. The detection of ultrastructural features that are usually associated with ABMR may help to establish ABMR as the cause of TMA. Conclusions: Although CNI and ABMR appear to be the main contributors to post-transplant TMA, the aetiology of most cases is probably multifactorial, and TMA cannot be unequivocally attributed to a single underlying aetiology. Morphological features of TMA are not discriminating, but electron microscopy may help to identify ABMR-associated TMA.

Original languageEnglish (US)
Pages (from-to)88-103
Number of pages16
JournalHistopathology
Volume75
Issue number1
DOIs
StatePublished - Jul 2019

Keywords

  • antibody-mediated rejection
  • calcineurin inhibitor
  • electron microscopy
  • kidney transplantation
  • thrombotic microangiopathy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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  • Cite this

    Broecker, V., Bardsley, V., Torpey, N., Perera, R., Montero, R., Dorling, A., Bentall, A., Neil, D., Willicombe, M., Berry, M., & Roufosse, C. (2019). Clinical–pathological correlations in post-transplant thrombotic microangiopathy. Histopathology, 75(1), 88-103. https://doi.org/10.1111/his.13855