Telomere length regulators are activated in young men after pediatric kidney transplantation compared to healthy controls and survivors of childhood cancer—A cross‐sectional study

Abstract

Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length‐regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere‐binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls. The influence of key clinical parameters on telomere length and on regulators of telomere length was evaluated. The telomere length in the KTx recipients tended to be shorter (0.53 AU) than in the healthy controls (0.64 AU) but longer than in the NBL survivors (0.38 AU). There was no significant difference in telomere length between the NBL survivors and the KTx recipients (P = .110). The gene expression level of telomere length‐preserving protein RPA1 was significantly higher in the KTx recipients than among the NBL survivors or healthy controls, while the expression of TRF2 and the tumor suppressor gene p16 was significantly higher in the KTX recipients when compared to the controls. TRF2 and TIN2 correlated significantly with hsCRP; additionally, TRF2 showed significant correlation with plasma creatinine and eGFR. KTx recipients have near to normal telomere length, but they have significantly higher gene expression levels of telomere regulatory proteins compared with healthy controls, suggesting activation of mechanisms preserving telomere length among KTx recipients. Our results suggest that declined graft function and consequent inflammatory response may have influence on telomerase activity.

Role of telomere length in human carcinogenesis (Review)

“…It is noteworthy that, as previously demonstrated, after kidney transplants, pediatric cancer patients exhibited a shorter blood cell telomere length compared to the controls, but presented with elevated gene expression levels of telomere length-preserving proteins ( 85 ). Therefore, also in renal cancer, a significant association between the variation of telomere length and cancer risk has been established.…”

Elderly patients with multiple comorbidities: insights from the bedside to the bench and programmatic directions for this new challenge in lung transplantation

“…This study also suggests that such genotypic analyses, targeting alterations typical of the accelerated aging process, may better tailor or personalize post‐transplant management leading to optimal post‐transplant outcomes. Another very recent interesting paper focused on pediatric renal transplant recipients that suggest activation of mechanisms preserving telomere length and telomerase activity regulating factors on the quality of allografts among young recipients appears to be in line with this direction .…”

Frailty in kidney transplant candidates and recipients: pathogenesis and intervention strategies

“…They also play a significant role in osteoporosis, which can result in bone disease after transplantation. Calcineurin inhibitors are nephrotoxic and reduce the activity of telomere-binding proteins, thus accelerating telomere length shortening and cell senescence [89] . In other respects, it has been reported that antibiotics and immunosuppressants can change the composition of the intestinal floras, thereby destroying the homeostasis of the intestinal system [90] .…”

“…Calcineurin inhibitors are nephrotoxic and reduce the activity of telomere-binding proteins, thus accelerating telomere length shortening and cell senescence. [ 89 ] In other respects, it has been reported that antibiotics and immunosuppressants can change the composition of the intestinal floras, thereby destroying the homeostasis of the intestinal system. [ 90 ] Once graft loss occurs, KT recipients will re-enter the ESRD stage and will require immunosuppressive therapy.…”