ESPN 51th Annual Meeting

ESPN 2018


 
Unexpected genetic background of early de-novo tacrolimus- related renal allograft thrombotic microangiopathy (TMA) in children.
URZYKOWSKA AGNIESZKA 1 JARMUżEK WIOLETTA 1 LATOSZYńSKA JOANNA 1 RUBIK JACEK 1 PROKURAT SYLWESTER 1 WóJCICKA ANNA 2 GRENDA RYSZARD 1

1- THE CHILDRENS MEMORIAL HEALTH INSTITUTE
2- WARSAW GENOMICS, MEDICAL UNIVERSITY
 
Introduction:

The cases of de-novo renal allograft trombotic microangiopathy (TMA) are regarded as related to adverse effect of immunosuppressive medications. Conversion between calcineurine inhibitors (CNIs) (tacrolimus;TAC) to cyclosporine;CsA) or from CNI to mTOR inhibitor is a major empirical management. Aim the study was to evaluate the genetic status of complement system in children with primary renal disease not related to hemolytic uremic syndrome (aHUS), who developed de novo TMA early after renal transplantation.

Material and methods:

Six patients (age 4-17 years), with non-aHUS related renal failure, undergoing renal transplantation (between 2013 and 2017), receiving triple immunosuppression (TAC+MMF+Pred), in whom symptoms of TMA: hemolytic anemia (free Hb 0.057-0.2 g/dL) and thrombocytopenia (64 000-98 000/µL) occured within first week post-transplant (1-6 days). Patients were treated with red cell (n=5) and/or fresh-frozen plasma (FFP; n=3) transfusions and all were converted from TAC to CsA (n=6); 1-2 days after TMA occurence. TAC dose was 0.14 - 0.25 mg/kg/day and blood through concentration 3.8 -18.7 ng/mL on the day of conversion. The genetic screening (NGS technique) was done retrospectively.

Results:

Platelet count normalized after 4-10 days after conversion (median 7 days). There was no acute rejection in either case. TMA has never recurred within > 1 year of follow-up. The presence of risky haplotype in CD46 gene (MCgaac) was confirmed in 4 children, risky haplotype variant of allele 1 of CFH gene in one and homozygotic deletion in CFHR1/2 with presence of anti-CFH abs (165,15 AU/mL) in one case.

Conclusions:

Conclusion: patients presenting early de-novo renal allograft trombotic microangiopathy, regarded as induced by tacrolimus, are at higher risk of TMA due to predisposing genetic mutations, silent before transplantation. The curative role of conversion from tacrolimus to cyclosporine A is unclear.