Aging and end stage renal disease cause a decrease in absolute circulating lymphocyte counts with a shift to a memory profile and diverge in treg population

Abstract

There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26±2y), healthy elderly (HEld) (n=15, 79±7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36±7y) and ESRD elderly (EnEld) (n=31, 65±3y) prior to Ktx regarding their naïve, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4+ memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required. (ClinicalTrials.gov number: NTC01631058).