Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure?

Abstract

Telomerase is involved in the elongation of telomeres. It remains active in very few types of cell in mature organisms. One such cell type is the lymphocytes. In this study, we investigated the activity and expression of telomerase in lymphocytes from renal failure patients and compared it to that for normal controls. Inflammation status was determined at the same time. The enzyme activity was measured using PCR-ELISA with peripheral blood mononuclear cells (PBMCs) from three groups: 53 healthy individuals, 50 patients with chronic kidney disease (CKD) and 50 dialysis patients. In the same cell populations, the expression of the reverse transcriptase of the human telomerase gene (hTERT) was measured via real-time PCR. The inflammationstatus of these individuals was determined by calculating the interleukin 6 (IL-6), IL-10, C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-a) serum concentrations via ELISA. The lowest levels of telomerase activity were detected in CKD, and this group had the highest IL-6 and CRP values and the lowest hTERT expression. The dialysis group showed significant differences in comparison to the normal subjects and to the CKD patients. Further studies are warranted in order to explore the way inflammation influences telomerase activity and hTERT expression.

The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?

“…Moreover, this activity was lower in patients with intermediate stages of CKD and not in dialysis ones, though the enzyme’s activity was also found to be pathological in dialysis when compared to normal controls. In addition, hTERT exhibited low levels of expression in intermediate stages of the disease but not in dialysis patients while our study also confirmed the inflammatory status of these patients [ 130 , 131 ]. Similarly, it has been reported that telomere length is affected from CKD duration when measured in DNA from whole blood samples.…”

“…TNF-a, CRP, IL-6, IL-1, IL-23, reactive oxygen species (ROS) and others, have all been implicated in promoting impaired renal function [ 129 ]. Impaired immunity/inflammation can be predictors of mortality and morbidity contributing to the risk of CKD and it seems very likely that telomeres/telomerase are very important aspects of this relationship [ 130 , 131 ]. Oxidative stress and chronic inflammation can cause lymphocyte telomere shortening resulting in T-cell dysfunction and ultimately susceptibility to kidney infection and injury.…”

Results from the German Chronic Kidney Disease (GCKD) study support association of relative telomere length with mortality in a large cohort of patients with moderate chronic kidney disease

“…7 In particular, it has been shown that chronic inflammation leads to lymphocyte telomere attrition, cell senescence, and finally impairment of the immune response. 8 This T-cell dysfunction can contribute to increased susceptibility to kidney infections and injury. 7 Chronic kidney disease (CKD) is a complex disease, and its heritability has been estimated to be 30%-70%.…”

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

“…[ 48 ] Furthermore, chronic low-grade inflammation may also be related to intracellular telomere reduction. Kordinas et al [ 49 ] reported that the levels of inflammatory mediators, such as IL-6 and CRP, increased and telomerase activity decreased in patients with CKD. This decrease in telomerase activity accelerates telomere shortening, thus accelerating cell senescence, the basis of frailty and aging.…”