Progressive immunosenescence in diabetic chronic kidney disease

Abstract

Abstract Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease in developed countries. It is known that patients with end-stage renal disease and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. We investigated level of immunosenescence in 770 Patients with type 2 diabetes with different levels of renal function. Consistent with previous observations in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. Compared to patients with eGFR>60 ml/min, patients with more severe CKD showed a progressive decrease in total CD3+ T cells, but not in monocyte numbers. Immunosenescence, as defined by multiple phenotypic markers, was significantly upregulated in both CKD stage 3 and stage 4/5 patients, especially of CD8+ T cells. In age and sex-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with eGFR>60 ml/min. In contrast, no change was detected in monocyte subpopulations as renal function declined. Our study indicates that therapeutic approaches to prevent the emergence of immunosenescence in renal failure patients should be implanted before stage 3 CKD.