Thrombotic Microangiopathy After Lung Transplantation: A Retrospective Observational Multicenter Cohort Study

TL;DR

Thrombotic microangiopathy (TMA) after lung transplantation is rare but deadly, with high mortality and limited treatment options.

Contribution

This study is the first multicenter cohort analysis of TMA after lung or heart-lung transplantation, focusing on outcomes and treatment strategies.

Findings

TMA occurred in 1.8% of lung transplant recipients, with a 48% mortality rate.

Belatacept therapy improved kidney function but increased adverse events like infections.

High CNI levels and combined CNI/mTOR therapy were major risk factors for TMA.

Abstract

Thrombotic microangiopathy (TMA) is a well-recognized complication of solid-organ transplantation that chiefly affects the kidneys. The objective of this study was to describe TMA features and outcomes after lung transplantation.

This retrospective observational study included patients with TMA following lung or heart-lung transplantation at eight French centers in 2006–2023. Univariate and multivariate analyses were done to identify factors associated with outcomes.

Of the 4565 patients, 82 (1.8%) experienced TMA, at a median of 19 [6−34] months after transplantation; among them, 79 were included (51% female; median age 50 [33−61] years). Mortality during the median follow-up of 31 [11−66] months was 38/79 (48%). Etiological factors were above-target calcineurin inhibitor (CNI) trough levels (48%), combined CNI and mTOR inhibitor therapy (23%), and infection (9%). CNI was continued in 70 patients and replaced by belatacept in 9 patients. In the belatacept group, renal function at one year was better but death, bacterial pneumonia, and CMV viremia were more common; none of the differences was significant, perhaps given the small sample size.

Mortality was high after TMA in lung or heart-lung transplant recipients. CNI monitoring protocols should be improved to minimize the risk of toxicity. Belatacept instead of CNI therapy was associated with better kidney function but also with higher frequencies of adverse events, suggesting a need for great caution. Studies adequately powered to assess the risk/benefit ratio of belatacept therapy according to the dosing regimen, patient features, and concomitant immunosuppressants are needed.

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