Effects of Aging on Kidney Graft Function, Oxidative Stress and Gene Expression after Kidney Transplantation

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.

Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double‐blind placebo‐controlled multicenter clinical study

“…Local activation of the renin–angiotensin system (RAS) in the kidney is an important mechanism in the occurrence and development of DN. At present, RAS blockers, which include angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are the only types of drugs for which there is an adequate evidence base showing that they reduce proteinuria levels in patients with DN and delay the progression of renal dysfunction . However, it remains very difficult to control overt proteinuria in patients with DN using RAS blockers, and residual proteinuria can promote the progression of DN.…”

Effects of Donor-Recipient Age Difference in Renal Transplantation, an Investigation on Renal Function and Fluid Proteome

“…They regulate metabolism and transport proteins and are responsible for regulating intracellular and extracellular signaling and expression, especially glucose metabolism and lipid metabolism. [19][20][21] Existing studies have demonstrated that high glucose promotes the senescence of renal mesangial cells, 22 and that abnormal lipid metabolism is an important risk factor for cell senescence. 23 Calorie restriction and pioglitazone (a drug regulating glucose metabolism) improve kidney aging.…”

Decreased expression of sirtuin 3 protein correlates with early stage chronic renal allograft dysfunction in a rat kidney model

“…A previous study conducted on 40 patients who had received kidney transplants demonstrated that increased MDA levels 1 day following kidney transplantation may be an early prognostic indicator of delayed graft function and increased levels on day 7 may be a useful predictor of 1-year graft function ( 11 ). Increased levels of MDA reflecting lipid peroxidation have been detected in rat models of chronic allograft tubular atrophy/interstitial fibrosis ( 18 ). In the current study, an increase in MDA levels and a decrease in SOD activity were detected in the renal tissues of rats in the allograft group, indicating that transplantation caused oxidative damage in the transplanted kidneys of rats in the early stage of CRAD.…”