P230
Clinicopathological Correlation of Transplant Associated Thrombotic Microangiopathy
Miriam Berry1, Victoria Bardsley2, Meryl Griffiths2, Sathia Thiru2, Nicholas Torpey1, Verena
Broecker2
1
2
Transplant Unit, Department of Histopathology,
Addenbrooke’s Hospital, Cambridge, United Kingdom
Introduction:
Transplant associated thrombotic microangiopathy (TA-TMA) is found in about 1% of renal
transplant biopsies. Many factors may contribute to aetiology and there are often discrepancies
between the histological, clinical and serological findings at the time of diagnosis. This
uncertainty has significant therapeutic implications.
Methods:
We performed a database search to identify all transplant patients diagnosed with TMA since
2008. Index biopsies were re-evaluated and scored using Banff criteria. Pathological
characteristics of TMA were assessed. All previous and subsequent histopathological, clinical
and serological data were reviewed and a final causal diagnosis was established following
clinicopathological conference. Diagnosis of calcineurin inhibitor (CNI) toxicity was based on
the absence of histopathological or clinical evidence of any other cause of TMA and
improvement following CNI withdrawal.
Results:
We identified 22 patients with TA-TMA and reviewed 84 renal transplant biopsies, 40 of which
showed TA-TMA. 85% were diagnosed within 12 months of transplantation. Patients with
ESRF due to immunological disease were over-represented in our cohort (45%), as were
recipients of HLA or ABO antibody incompatible grafts (23%).
Antibody Mediated Rejection (AMR) and CNI toxicity were the two commonest causes of TATMA (41% and 36%, respectively). Histopathological characteristics of TA-TMA were not
significantly different between these groups. In 5/13 patients with DSA, TA-TMA occurred in
the absence of microcirculation injury (C4d positive in 4/5 cases). All were considered as a
manifestation of AMR in the presence of significant DSA.
10/22 patients showed acute vascular rejection in at least one of their biopsies (3 Banff v1
lesions, 4 Banff v2, 3 Banff v3). In 2 patients this T cell mediated rejection (TCMR) was the
only likely cause of TMA. Neither had detectable DSA at any time.
The outcome was bimodal; 6/22 patients reached end stage renal failure while the remainder
returned to baseline renal function. 5/6 graft losses had AMR.
Conclusions:
Morphological characteristics of TA-TMA are of limited value in identifying the underlying
cause. AMR was the commonest cause of TA-TMA, the only manifestation of AMR in some
cases and associated with poor renal outcomes. CNI related disease responded to drug
withdrawal and this group had much better renal outcomes.
Cell mediated vascular rejection was seen in 45% patients, indicating the role of endothelial
injury in a multifactorial process. Multiple hits are likely to precipitate TMA:
underlying
susceptibility, vascular injury and an additional trigger such as CNI.