Verena Broecker1,2, Victoria Bardsley2, Nicholas Torpey3, Ranmith Perera4, Rosa Montero5, Anthony Dorling6, Andrew Bentall7, Desley Neil8, Michelle Willicombe9, Miriam Berry3, Candice Roufosse10,11. 1. Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden. 2. Department of Histopathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 3. Department of Clinical Nephrology and Transplantation, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 4. Department of Cellular Pathology, St Thomas' Hospital, London, UK. 5. Department of Nephrology, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK. 6. MRC Centre for Transplantation, King's College London, London, UK. 7. Department of Nephrology and Transplantation, University Hospital Birmingham, NHS Foundation Trust, Birmingham, UK. 8. Department of Histopathology, University Hospital Birmingham, NHS Foundation Trust, Birmingham, UK. 9. Department of Medicine, Hammersmith Hospital, Imperial College Health Care NHS Trust, London, UK. 10. Faculty of Medicine, Imperial College, London, UK. 11. Department of Cellular Pathology, North West London Pathology, London, UK.
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.
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.
Authors: Anthony Sabulski; Grace Arcuri; Sara Szabo; Marguerite M Care; Christopher E Dandoy; Stella M Davies; Sonata Jodele Journal: Blood Adv Date: 2022-07-26