MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
Creators
- 1. Institute of Clinical and Experimental Medicine
- 2. First Faculty of Medicine, Charles University, Prague, Czechia
- 3. Research Laboratory, Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Description
De novo thrombotic microangiopathy (TMA) is associated with poor kidney
graft survival, and as we previously described, it is a recipient driven process
with suspected genetic background. Direct Sanger sequencing was performed
in 90KTRwithdenovoTMAand90correspondingdonorsonselectedregions
in CFH,CD46,C3,andCFBgenesthatinvolvevariations withafunctional effect
or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did
not develop TMA were analyzed for the MCPggaac haplotype. Three-years
death-censored graft survival was assessed usingKaplan-Meier andCox
regression models. The distribution of haplotypes in all groups was in the
Hardy-Weinberg equilibrium and there was no clustering of haplotypes in any
group. In the TMAgroup,wefoundthatMCPggaachaplotypecarriers wereata
significantly higher risk of graft loss compared to individuals with the wild-type
genotype. Worse 3-year death-censored graft survival was associated with
longer cold ischemia time (HR 1.20, 95% CI 1.06, 1.36) and recipients’
MCPggaac haplotype (HR 3.83, 95% CI 1.42, 10.4) in the multivariable Cox
regression model. There was no association between donor haplotypes and
kidney graft survival. Similarly, there was no effect of the MCPggaac haplotype
on 3-year graft survival in recipients of paired kidneys without de novo TMA.
Kidney transplant recipients carrying the MCPggaac haplotype with de novo
TMA are at an increased risk of premature graft loss. These patients might
benefit from therapeutic strategies based on complement inhibition.
Notes
Supported by the Ministry of Health of the Czech Republic NU22-C-126 and by its conceptual development of research organizations (Institute for Clinical and Experimental Medicine – IKEM, IN 00023001). Supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, Project No. LX22NPO5104) - Funded by the European Union - Next Generation EU. Project no. TKP2021-EGA-24 (MOLORKIV) has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. DC received research funding from the Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences (PPD2018-016/2018).
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