Abstract
Conflicting results have been reported regarding the effects of donor age, recipient age and donor-recipient age difference on short- and long-term outcomes after kidney transplantation. The aim of this study was to evaluate the effects of recipient age on graft function, oxidative stress, and gene expression after renal transplantation. Fifty male Fischer 344 rats [25 young (Y, 4 months), 25 senior (S, 16 months)] were randomized to 6 groups: 2 sham groups (Y and S, n = 5 in each group) and 4 renal transplant groups[young-to-young (Y-Y), young-to-senior (Y-S), senior-to-young (S-Y), senior-to-senior (S-S), (n = 10 in each group)]. The left kidneys were transplanted from donor to recipient. After 12 weeks, systematic blood pressure, graft weight, graft function, histology and oxidative stress were measured. Microarray analysis and quantitative real-time PCR confirmation were performed to study gene expression in the grafts. There were no differences in renal graft function between young and senior kidney cross-transplantation. Transplanted kidneys showed no significant differences in glomerulosclerosis index compared to non-transplanted kidneys but had significantly different tubulointerstitium scores compared to age-matched controls. Senior rats had lower SOD activity and higher MDA content than young rats. SOD activity was significantly lower and MDA content significantly higher in the Y-S group than in the Y-Y group. There were 548 transcript differences between senior and young kidneys with 36 upregulated and 512 downregulated transcripts. There were 492 transcript differences between Y-S and Y-Y groups with 127 upregulated and 365 downregulated transcripts. There were 1244 transcript differences between the S-Y and S-S groups with 680 upregulated and 574 downregulated transcripts. Oxidative stress and gene expression profile was significantly different in the Y-S compared to the S-Y group. The identified differences were mainly in the MAPK and insulin signal pathways, making these potential targets for therapeutic intervention.
Highlights
Kidney transplant (KT) donors [1] and recipients [2] are increasingly elderly
The positive rate of staining for SA-b-gal was significantly higher in senior compared to young kidneys, and levels were significantly higher in the Y-S group than in the Y-Y group; in addition, levels were significantly lower in the S-Y group compared to those in the S-S group (Fig. 1, Table 2)
The main findings of our study were that: 1. kidney aging occurred in this KT model; 2. aging itself did not influence renal function after KT; 3. accumulation of oxidative stress may be related to the aging effects observed; 4. the change in gene expression profile was different in young and old rat kidneys; these changes were apparent in different pathways: energy metabolism, extracellular matrix (ECM), immunological inflammation, proliferation, differentiation, and apoptosis; 5. the p53-p21, Mitogen-activated protein kinase (MAPK) and insulin signaling pathways may be involved in regulation of these responses
Summary
Kidney transplant (KT) donors [1] and recipients [2] are increasingly elderly. The growing numbers of patients with endstage kidney disease, and improvements in short-term KT outcomes, have increased the number of patients who are at risk of the long-term complications of KT. Despite improvements in KT techniques, whether and how donor and recipient age affect graft function and patient survival after KT remain debatable. If transplanted kidneys age at an accelerated rate relative to other organs in the recipient, slowing or reversing this process may be a useful strategy to improve outcomes after KT. Reduced oxidative damage, as shown by reduced levels of oxidation and apoptosis, at 6 months after transplantation correlated with a better recovery of renal function in kidney allografts [13]
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