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Uremia may provoke immune senescence in patients with CKD
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Patients with chronic kidney disease have a greater likelihood of premature immune aging and age-related disease, according to recently published findings.
Thomas Crépin, MD, and colleagues prospectively identified 222 outpatients seen at the nephrology department of the University Hospital of Besancon between Sept. 1, 2013 and Aug. 1, 2016. Researchers stratified patients into three groups based on CKD stage: group 1, with normal kidney function (eGFR greater than 60 mL/min/1.73 m2, modification of diet in renal disease [MDRD] equation or creatininemia less than 120 mmol/L, n=85; group 2, with severe, stage 4 kidney disease (eGFR between 15 and 30 mL/min/1.73 m2 , MDRD, n=53) and group 3, which included patients on dialysis with ESRD (hemodialysis, n=47, peritoneal dialysis n=37).
Cytometry on T-cells or quantitative polymerase chain reaction (relative telomere length) on peripheral blood mononuclear cells was used to evaluate biomarkers of immune aging. Researchers analyzed these biomarkers based on CKD stages and outcomes. The following were documented as clinical outcomes: death and causes, cardiovascular events and infections necessitating hospitalization, and antibiotics or antiviral treatment. As the patient populations were significantly different in terms of age and gender, researchers conducted an analysis of immune senescence biomarkers on 105 patients matched for age, gender and cytomegalovirus (CMV) status.
In the matched group, progression of CKD was associated with increased CRP (median, 2.9 mg/L) in group 1 vs. 5.1 mg/L in group 2 vs. 6.2 mg/L in group 3. CKD progression was also linked to higher ferritin levels in group 1 (median 142 ng/mL) vs. 134 ng/mL in group 2 vs. 246 ng/mL for group 3. Inverse associations were seen between eGFR and CRP and ferritin levels (r=-0.22; P=.025 for CRP and r= -.20; P=.037).
(20±10% in group 1 vs. 15±9% in group 2 vs. 9±13% in group 3) and absolute counts (197±25 RTE/mm3 in group 1 vs. 88±13 RTE/mm3 in group 2 vs. 73 ±21 RTE/mm3 in group 3).
A significant increase in terminally differentiated CD8+ T cells was seen in CMV-positive patients based on CKD stage (27±20% in group 1 vs. 37±15% in group 2 vs. 43±16% in group 3). However, no differences between groups were seen in terminally differentiated CD8 + cells in patients without CMV.
CKD also correlated with shortening of telomeres (1.11± 0.36 vs. 0.78±0.24 vs. 0.97±0.27 telomere/single copy ratio in groups 1 to 3, respectively ) and increased C-reactive protein concentrations (median 2.9 mg/L vs. 5.1 mg/L vs. 6.2 mg/L in groups 1 to 3, respectively). Multivariate analysis revealed shorter relative telomere length correlated with mortality (HR: 4.12). Associations were seen between low thymic output and infections (HR: 1.79) and terminally differentiated CD8+ expansion of T cells with a risk of cardiovascular events (HR: 4.86).
“CKD, even before ESRD and dialysis, is associated with features of immune senescence,” the researchers wrote. “Uremia-induced immune senescence parameters are associated with poor clinical outcomes.” – by Jennifer Byrne
Disclosure: Vauchy, a co-author of the study, reports grants from Region France-Comte and Santelys.