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. 2021 Feb 12;7(1):8. doi: 10.1186/s41100-021-00324-0

Table 1.

Review of NK cell function in end-stage kidney disease

Summary Study design Results and interpretation Ref., year
C↓ Comparison between three dialyzer membranes of different composition on suppressing NK activity. Biocompatibility of hemodialyzer membrane affects the significance in impairment of human NK cell cytotoxic function. [9], 1987
C↓ Comparing NK cell activity of PBMC between maintenance HD patients and healthy control. NK cell cytotoxic activity in patients on HD was two thirds of healthy control. Although urea did not suppress the NK cell activity, the guanidino compound did significantly. [10], 1988
N↓ C↓ Comparing cell activity of NK cell number among 20 undialyzed ESKD patients, 25 patients on HD patients, patients on PD, and healthy control. NK cells were morphologically determined as large granular cells. In groups of ESKD patients, HD and PD, NK cell number and activity were reduced to less than half of the control group. Particularly, HD patients on cuprophane membrane have an additional negative effect on NK cells. [20], 1990
N↑ C↓ A prospective study of 8 patients on HD using cuprophane membrane for 2 weeks. NK cells were analyzed by flow cytometry. After exposure of cuprophane membrane, CD56+ NK cells increased from 28 to 59% in peripheral blood lymphocytes and decreased cytotoxicity from 29 to 12%. [19], 1993
N↑ C↓ Counting peripheral NK cells (CD3CD56+ and CD3CD16+) in 35 patients on HD. HD elicits higher proportions of NK cells and decrease in their cytotoxic activity compared with the control group. [11], 1996
N↑ Lymphocyte subpopulation analysis in 34 patients on HD and 37 patients on PD The HD and CAPD patients showed increased percentages of NK cells (CD3CD16+CD56+). [18], 2005
N↓ C→ R→ Phenotyping NK cells in 210 patients on HD, undialyzed uremic control and healthy volunteers. Functional assay was performed with matching for NK cell count. NKp30, NKp46, NKG2D, and CD226 were examined as activating NK receptors. In undialyzed patients, lowered NK cell counts were associated with reduced renal clearance. NK counts in HD patients were lower than in healthy control. NK cell functions were similar in subgroups of HD and healthy control. The expression of receptors modulating NK cytotoxicity was not altered. [22], 2008
N→ C↓ Functional analysis of CD3+CD16+ NK cells from 33 HD patients and 30 healthy donors. Expression level of CD3 zeta-chain in NK cells was evaluated. NK cell counts did not differ between HD patients and healthy donors. NK cell zeta-chain downregulation in HD patients seems to contribute to the decreased NK cell activity. [24], 2008
N→ C↓ R↓ L↑ Comprehensive characterization of NK cell number and cytotoxic function in 66 ESKD patients (59 patients on HD and 7 patients on PD), and experiments to show the function of NK receptors and their ligands in uremic status. While total NK cell proportion was comparable, patients on chronic dialysis showed a profound decrease in NKG2D+ NK cells comparing to healthy donors (56% vs 39%). Combined with increased expression soluble ligands for NKG2D in uremia, NKG2D-mediated NK cytotoxic function was impaired in ESKD patients. [27], 2009
N↑↓ Lymphocyte subset in peripheral blood from 472 CKD patients (G1, n=88; G2 n=93; G3, n=88; G4, n=68; n=135) was examined. Proportion of CD16+CD56+ NK cells was 9.2 (G1), 10.8 (G2), 12.9 (G3), 13.5 (G4), and 12.8% (G5) in CKD. On contrary, absolute lymphocyte count was substantially decreased from 2.04 (G1) to 1.48 × 109/L (G5). [23], 2016

N Number of natural killer (NK) cells, C Cytotoxic function of NK cells, R Expression of NK receptors, L Ligand expression of activating receptors, ESKD End-stage kidney disease, PBMC Peripheral blood mononuclear cells, HD Hemodialysis, PD Peritoneal dialysis, NKp30, -p40 Natural killer cell p30-related protein, p-46 related protein, NKG2D Natural killer group 2 member D