Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients

Abstract

Background: Natural killer (NK) cells provide a first line of immune defence towards infections and tumours, and participate in atherosclerosis and pregnancy diseases, of which there is a higher incidence in uraemic patients. Still, their relative contribution to the immunodeficient state associated with renal failure is poorly documented.

Methods: A multivariate and comparative analysis of lymphocyte subsets in haemodialysed (HD) and undialysed (UD) uraemic patients in comparison to healthy donors (HC) is provided in this article. NK-mediated cytotoxicity, degranulation and interferon secretion were compared in HD and HC.

Results: Evaluation of NK cells in 210 HD patients concluded with a decrease in NK cell counts in comparison to HC. Multivariate analysis associated lowered NK cell counts in UD patients with decreased renal clearance and higher NK counts HD with male gender and age. The 32% NK cell count decrease observed in sex- and age-matched groups (n = 88) was associated with B- and CD8(+)T-lymphocyte defects. NK cell functions were similar in subgroups of HD and HC matched for NK cell counts. Longer dialysis duration was associated with improved NK cytototoxic activity. While the expression of receptors modulating NK cytotoxicity were not modified, expression of the activation markers CD69 and NKp44, CD94 and chemokine receptors CX3CR1 and CXCR4 was altered in HD.

Conclusions: This study is the first to associate decrease in renal function with selective fading of NK cell number and identify haemodialysis duration as a factor influencing NK cell function. It further shows that lower cell counts rather than intrinsic NK cell dysfunction per se characterize immune disorders in HD.