Replicative senescence in patients with chronic kidney failure.
BACKGROUND
Chronic activation of immunocompetent cells may lead to stress-induced premature senescence (SIPS); these senescent cells are characterized by a decrease in telomere length. The present study evaluates SIPS in circulating immunocompetent cells from predialysis patients, patients on hemodialysis, and in renal transplant patients with normal renal function.


METHODS
Determination of telomere length by flow-fluorescence in situ hybridization (FISH), expression of surface molecules, and evaluation of apoptosis was performed by flow cytometry.


RESULTS
In uremic predialysis patients, we observed a subpopulation of lymphocytes with short telomeres. However, in this population of patients we did not observe SIPS mononuclear cells. In hemodialysis patients, we found a subpopulation of SIPS mononuclear cells that also showed phenotypic changes of proinflammatory activity. Finally, transplant patients with normal renal function also exhibited a subpopulation of SIPS lymphocytes, which can be attributed to chronic lymphocyte activation induced by the major histocompatibility complex.


CONCLUSIONS
In chronic kidney disease patients, immunocompetent cells undergo SIPS, a process associated with chronic cell activation and induced by numerous stimuli including uremia, hemodialysis membranes, and bacterial products. Because SIPS immunocompetent cells are activated cells with proinflammatory features and live longer in peripheral blood, it is likely that SIPS cells contribute significantly to the chronic inflammatory state of patients with advanced renal failure.
Jimenez
Rosario
R
Servicio de Nefrología, Unidad de Investigación, Hospital Universitario Reina Sofía, Córdoba, Spain.
Carracedo
Julia
J
Santamaría
Rafael
R
Soriano
Sagrario
S
Madueño
Jose A
JA
Ramírez
Rafael
R
Rodríguez
Mariano
M
Martín-Malo
Alejandro
A
Aljama
Pedro
P
D017209:Apoptosis; D002470:Cell Survival; D016922:Cellular Senescence; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D008285:Major Histocompatibility Complex / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D006435:Renal Dialysis; D016615:Telomere / Q000648:ultrastructure; D014511:Uremia / Q000276:immunology / Q000503:physiopathology