The Affection Of Renal Transplantation Donor-Recipient Age Difference To Graft Function And The Proteome Of Recipient

Objection:The shortage of organ donors limited the development of kidney transplantation.And living donor transplantation play an effective role in helping to deal with this problem.The number of centers which choose old living donors for living transplantation is increasing world widely.But with the increasing of the old living donors'age,the influence on the outcome of the renal transplantation from donors' age and donor-recipient age differences is becoming obviously.And the long-term result of renal transplantation from old living donor is still under debating especially when recipients are young.How new bodily internal environment will impact the senescence process of aging graft after transplanted into younger recipient.And how the senescence process of recipients' internal environment and graft influence the long-term outcome of graft.This study focuses on estimating the outcome by donor-recipient age difference living kidney transplantation,with the proteome of donors' and recipients' serum or urinary,to explores weather the aging internal milieu will affect the graft.Method:20 young recipients and their corresponding old donors,and 6 old recipients and their corresponding young donors were included in this study.All the relationship between recipients and donors is parent-children.Their kidney functions were tested and compared by SPSS 22 software in pair T test.Then we analyzed the serum and urinary proteome of 5 pairs cases in two groups by LC-MC proteomic mass spectrum technique.The data was searched against the target-decoy RefSeq human database.Wilcoxon-Mann-Whitney test were applied to select data sets.And we landed GO and IPA database to identify proteins by bioinformatic and pathway analysis.Result:1.The average age of twenty old donors is 57-year-old,and their average eGFR is 69.27 ml/min.The average age of twenty young recipients is 3 3-year-old and their average eGFR is 74.07 ml/min.The average age of six young donors is 38-year-old.and their average eGFR is 97.69 ml/min.The average age of six old recipients is 62-year-old,and their average eGFR is 64.46 ml/min.The kidney function of old donors and young recipients' are similar while young donors' are better than old recipients'(p=0.222,p=0.036).2.We identified 497 proteins in serum proteome of 10 cases of 5 pairs in two groups.We compared the proteome data between old donors and young recipients,young donors and old recipients.There are 17 distinct proteins in old donor-young recipient group and all these distinct proteins are highly expressed in the serum of old donors.There are 12 distinct proteins in young donor-old recipient group and all these distinct proteins are highly expressed in the serum of old recipients.The common pathways of distinct proteins in two group are Acute Phase Response Signaling,FXR/RXR Activation and LXR/RXR Activation.And SLC3A2 is the only distinct exists in both two group.3.We identified 975 proteins in urinary proteome of 10 cases of 5 pairs in two groups.There are 12 distinct proteins in old donor-young recipient group and 4 of these distinct proteins are highly expressed in the urinary of old donors,8 distinct proteins are lowly expressed.There are 28 distinct proteins in young donor-old recipient group and 15 of these distinct proteins are highly expressed in the urinary of old recipients while 13 distinct proteins are lowly expressed.The common pathways of distinct proteins in two group are Acute Phase Response Signaling,Atherosclerosis Signaling,Clathrin-mediated Endocytosis Signaling,Coagulation System,FXR/RXR Activation,LXR/RXR Activation and Neuroprotective Role of THOP1 in Alzheimer's Disease.SERPINA1 and SERPINA3 exist in both two group in the meantime.Conclusion:1.The donor-recipient age difference influences the graft function and this may because of graft aging speed is changing induced by the difference of internal milieu.2.The serum proteins of old individuals and young individuals are different.These different proteins are related with immune response,energy metabolism etc.Among the distinct proteins,SLC3A2 is related to internal milieu senescence process.3.Renal transplantation can change the urine proteome and these distinct proteins are associated with immune response,energy metabolism,arteriosclerosis etc.Among these proteins,SERPIN1 and SERPINA3 are associated with renal transplantation.