De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus

Abstract

A prompt diagnosis of de novo TMA by early allograft biopsy is essential for the allograft outcome and genetic investigations for possible complement abnormalities are reasonable, not only for patients with a systemic aspect of their post-transplant TMA. Replacing tacrolimus with everolimus effectively controlled the TMA and stabilised renal function in our patient.

Therapeutic plasma exchange in children: One center's experience

“…He did not respond to TPE in conjunction with immunosuppressive treatment (tacrolimus, steroids, IVIG, ATG, rituximab) and progressed to ESRD. Interestingly, he developed calcineurin inhibitor‐induced TMA soon after retransplantation, which resolved with conversion from tacrolimus to everolimus …”

Calcineurin inhibitor-induced endothelial cell injury – A role for complement

“…Its use is associated with significant nephrotoxicity, ranging from acute vasoconstriction to chronic tubular and vascular injury, and less commonly, thrombotic microangiopathy (TMA). (AlMassarani et al, 2008;Al-Nouri et al, 2015;Bren et al, 2005;Cortina et al, 2015;Jiang et al, 2014;Lin et al, 2003;Naesens et al, 2009;Rodrigues-Diez et al, 2016;Zarifian et al, 1999) CNI toxicity negatively impacts allograft survival and may be a contributory factor to the lack of improvement in long-term allograft survival which has remained stagnant over the last few decades.…”

“…(Al-Nouri et al, 2015;Bren et al, 2005;Cortina et al, 2015;Lin et al, 2003;Ponticelli, 2007) TMA associated with the use of CNIs can present with a clinical picture resembling acute hemolytic-uremic syndrome, which in severe cases can lead to transplant allograft loss. (Ali et al, 2013;Caires et al, 2012;Furmanczyk et al, 2009;Gray and Ameduri, 2016;Parissis et al, 2010;Said et al, 2010) However, TMA can also occur without overt systemic clinical manifestations.…”

“…(Al-Nouri et al, 2015;Ali et al, 2013;Bren et al, 2005;Caires et al, 2012;Cortina et al, 2015;Furmanczyk et al, 2009;Gray and Ameduri, 2016;Lin et al, 2003;Parissis et al, 2010;Ponticelli, 2007;Said et al, 2010;Zarifian et al, 1999) The primary aim of this thesis is to examine whether cyclosporine exposure lead to complementmediated endothelial cell injury and to elucidate the mechanism by which complement dysregulation is induced. To achieve this, we used an in vitro model of disease that utilizes human blood outgrowth endothelial cells (BOEC), because they are an endothelial progenitor cell that can be isolated from patients.…”

“…(Gilbert et al, 2013) CFH risk polymorphisms were found in a patient with CNI-induced thrombotic microangiopathy postkidney transplant. (Cortina et al, 2015) 1.3.5 Genetic susceptibility predispose to manifestation with thrombotic microangiopathy 1.3.6 Implications for a role for complement in calcineurin inhibitor toxicity…”