THE EFFECT OF CHRONIC KIDNEY DISEASE AND DIALYSIS MODALITIES ON THE EXPRESSION OF T REGULATORY (CD4+CD25+FOXP3+) AND NATURAL KILLER (CD56+CD16+) CELLS

Abstract Background and Aims Tregs regulate immune responses and maintain self-tolerance, while Natural Killer cells (NK) are cytotoxic lymphocytes critical for both adaptive and innate immunity. The presence of chronic kidney disease (CKD) is often characterized by disturbances in immune responses, including dysregulation between tolerance and cytotoxicity. Aim of the present study was to evaluate the influence of CKD on the Tregs (CD4+CD25+FoxP3+) and NK cells, as well as the effect of hemodialysis (HD) and peritoneal dialysis (PD) on these subtypes. Method A total of 40 CKD Stage V patients and 15 healthy volunteer subjects were recruited into our study. Peripheral Tregs and NK cells were isolated from whole blood samples using flow cytometry, and the results were compared to those of age and gender matched controls. The immunologic profile of CKD patients was repeated 6 months after HD initiation (n=20) and PD (n=20) in order to investigate the effect of different dialysis methods. Results Patients with CKD had significantly reduced populations of CD4+CD25+ FoxP3+ Tregs (47.5± 28.8 vs 71.5±24.7) p=0.01, while there was no difference in NK cells between patients and controls (16.4±8.1% vs. 13.4±9.1%), p=NS, respectively. There were no differences between patients started on HD or PD in terms of clinical and laboratory parameters. Frequencies and total numbers of Tregs were significantly reduced after 6 months of HD, from 7.6±2.1% to 5.2±2.3%, p=0.009, and from 53.6±26K/μL to 36.9±19K/μL, p=0.02, respectively, while showed no differences on PD patients, from 5.3±3.3% to 5.6±2%, p=NS and 33.2±27K/μL to 45.6±28K/μL, p=NS, respectively. NK cells were increased in HD patients, not reaching statistical significance (245±156K/μL to 261±128K/μL). Frequencies of NK cells were positively correlated with CRP (r=0.56, p=0.009) and Intimal media thickness (IMT) (r=0.48, p=0.03) Conclusion The results of our study show that initiation of hemodialysis (HD) seems to reduce the expression of CD4+CD25+FoxP3+ T cells while peritoneal dialysis (PD) doesn’t seem affect this cell population. The immune alterations observed in hemodialysis patients may have a clinical impact on chronic inflammation and atheromatosis.