PRE-TRANSPLANT AT1Rab AND THEIR ROLE IN KIDNEY TRANSPLANTATION Terasaki Festschrift Los Angeles CA, January 2014 EA Hernández-Méndez, JM Arreola, LE Morales-Buenrostro, MI Salcedo, J Ramírez, S Calleja, M Vilatoba, AG Contreras, J Granados, B Gabilondo, J Alberú. Transplant and Nephrology-Mineral Metabolism Departments InstitutoNacional de CienciasMédicas y Nutrición Salvador Zubirán Mexico City
Angiotensin II type 1 receptor Chromosome 3 7 TM domains 14 polymorphisms A1166C Mediator of Ang-II cardiovascular effects Reinsmoen N. Transplantation 2010; 90; 1473
AT1Rab Autoantibodies Alloantibodies IgG1 and IgG3 No C4d deposition Reinsmoen N. Transplantation 2010; 90; 1473
AT1Rab AT1R PKC G ERK1/2 TF NF-KB MCP AP-1 Nucleus RANTES Dragun D. Hum Immunol 2012; 73: 1282
AT1Rab and kidney transplant Reinsmoen N. Transplantation 2010; 90; 1473. Giral M. Am J Transpl 2013; 10: 2567. Taniguchi M. Am J Transpl 2013; 13: 2577.
Objectives • To evaluate the renal graft´sfunction and BPAR eventsduring the 1st year posttransplant in living-donorkidneytransplantrecipients with pre-transplant +ve AT1Rabs. • To document the frequency and effects of AT1Rab in anadult, healthypopulation (livekidneydonors).
Methods • Retrospective cohort study. • KTR and their LKD (n=114) • Mar 2009 - Aug 2012. • Sera obtained the day before KT and kept frozen at -70ºC. • KTR sera: screening for of AT1Rabs (ELISA) and HLA-DSA (Luminex). • LKD: determination of AT1Rabs. AT1Rab positive titers ≥17 IU DSA positive MFI ≥ 500
Pre-transplant AT1Rab in KTR (n=111) 3 groups according to serologic status: KTR with both AT1Rabs and HLA-DSA were excluded (n=3)
Main outcomes in KTR (n=111) *1 patient with evidence of both cellular and humoral rejection **2 patients with evidence of both cellular and humoral rejection
eGFR at different time pointsduringthe 1st yearposttransplant eGFR at different time points during the 1st year posttransplant
Pre-Tx AT1Rab associated with lower PT eGFR Multivariate lineal regression analysis of eGFR deterioration at 12 mo PT
What about AT1Rab in LKD? 2 groups (n=113) according to pre-nephrectomy serologic status: All LKD were strictly non-obese and normotensive
Summary • Positive AT1Rabs were an independent and significant risk factor associated with lower eGFR beginning in the early PT period. • eGFR deterioration was higher in the AT1Rab than in the HLA-DSA +ve group. • More BPAR during 1st year PT occurred in AT1Rab +ve KTR. • AT1Rabs are apparently innocuous to renal function at 1-year post-N in LKD. • Longer follow-up is necessary in both populations in order to draw final conclusions.