B Doucet1,2, S Dheda3, M Fahim1,2, D Mudge1,2, C Hawley1,2, D Johnson1,2, P Hopkins2,4, N Isbel1,2

1Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland; 2School of Medicine, University of Queensland, Brisbane, Queensland; 3Department of Nephrology, Cairns Base Hospital, Cairns, Queensland; 4The Prince Charles Hospital, Brisbane, Queensland

Aim: To examine the association between transplant associated thrombotic microangiopathy (TA-TMA) post non-renal solid organ transplant and mutations of complement regulatory pathways.

Background: TA-TMA is a rare and potentially fatal complication of transplantation.  Patients that develop TA-TMA may have an underlying complement regulatory factor mutation, as seen in atypical haemolytic uraemic syndrome.  We present a case series of five patients with non-renal solid organ transplants who developed TA-TMA and subsequently underwent genetic screening.

Methods:  Patients cared for by our institution with non-renal solid organ transplant who developed TA-TMA underwent genetic screening.  The entire coding region of the ADAMTS13, C3, CD46, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR5, CFI, DGKE, MMACHC, PIGA, THBD genes were analysed.  All identified variants were evaluated regarding their pathogenicity and causality.

Results: Five transplant recipients with renal biopsy-proven TA-TMA were evaluated (three female; 4 lung transplants, 1 liver transplant). Average time from transplantation to diagnosis was 6 months.  Mutations of uncertain significance were identified in four patients.  Four patients experienced improved renal function on maintenance eculizumab.  The one patient with no identified genetic abnormality received eculizumab for 12 months and has since remained in remission following cessation.  In patients treated with eculizumab, average estimated glomerular filtration rate improved from 18.3 to 47.5 ml/min/1.73m2. The remaining patient had developed dialysis-dependent renal failure before recognition of TA-TMA.

Conclusions:  Eculizumab was associated with resolution of microangiopathic haemolytic anaemia and stabilisation or improvement in renal function in patients with TA-TMA.  Further study of complement regulatory pathway mutations in non-renal solid organ transplant recipients with TA-TMA is warranted.

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