Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patients.

Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients' characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 +/- 21.49 vs. 5.51 +/- 4.57 pg/mL (P<0.018) and TChol 167.37 +/- 47.84 vs.122.04 +/- 26.48 mg/dL (P<0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 +/- 11.54 vs. 23.15 +/- 18.76 mg/L (P<0.000) and TChol 169.26 +/- 46.42 vs. 133.26 +/- 46.33 mg/dL (P<0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130)--an antagonist of IL-6 action--were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients.

Release of interleukin-6 and its soluble receptors by activated peripheral blood monocytes is elevated in hypocholesterolemic hemodialysis patients.

BACKGROUND: A reverse association between cholesterol level and cardiovascular disease mortality is observed in hemodialysis (HD) patients; this paradoxical relationship may be explained by the coexistence of inflammation. Interleukin-6 (IL-6) is a central regulator of inflammation; its action is augmented by the soluble IL-6 receptor (sIL-6R) and inhibited by the soluble gp130 (sgp130). In order to investigate the potential association of inflammation with cholesterol levels in the HD population, release of soluble IL-6 components by peripheral blood mononuclear cells (PBMCs) was measured in two groups of HD patients with distinctly different lipid profile and in a control group. METHODS: Twenty-two HD patients with low serum cholesterol (range 85-171 mg/dl), 23 HD patients with high cholesterol (189-342 mg/dl) and 21 normolipidemic non-renal failure subjects were enrolled in the study. IL-6, sIL-6R and sgp130 were measured by ELISA in the serum and in the supernatant collected from cell cultures of activated or resting PBMCs isolated from all three groups. RESULTS: Serum IL-6 and sgp130 level was higher while sIL-6R was lower in both groups of HD patients compared to the control group. The ex-vivo release of the IL-6 and sgp130 by unstimulated PBMCs did not differ significantly between the three groups but that of the sIL-6R was higher in non-renal failure than in hypercholesterolemic HD subjects. Production of sIL-6R by stimulated PBMCs was higher in low-cholesterol HD patients (p < 0.001) and the same was valid for the sgp130 release (p = 0.034). Release of IL-6 by activated PBMCs was higher in the low-cholesterol compared to the high-cholesterol HD patients group (p = 0.011 for post hoc test). Major serum lipid fractions were inversely correlated to IL-6 and sIL-6R production from stimulated PBMCs in HD but not in non-renal failure subjects. Finally, release of the sgp130 by PBMCs was significantly reduced in 13 hypertriglyceridemic--and hypercholesterolemic--HD patients. CONCLUSION: Production of soluble components of a crucial pro-inflammatory and potentially atherogenic cytokine, namely the IL-6, by stimulated PBMCs appears to be inversely correlated with the serum cholesterol levels in HD patients.