Background: Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects. Methods: In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 ± 12.4 and 51.4 ± 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol. Results: Telomerase activity in PBMCs was detected in 18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renal- failure (117 ± 112 %) than in HD (47.6 ± 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 ± 8.9 vs. 75.0 ± 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs. Conclusion: Telomerase activity in PBMCs is reduced in HD patients. It seems that, at least in this type of cell in this population, defense from senescence, as assessed by telomerase activity, is altered and associated with the chronicity of uremia/HD procedure.

Calciphylaxis (calcific uremic arteriolopathy) is a severe complication of hemodialysis characterized by subcutaneous calcification of the small arteries and tissue necrosis. Our case report is focused on a woman receiving hemodialysis (HD) with diabetes mellitus for 20 years and severe secondary hyperparathyroidism, who presented painful subcutaneous nodules, skin necrosis and ulcerations. As the treatment of calciphylaxis is mainly empirical and controversial, we decided to administer cinacalcet with paricalcitol for the control of hyperparathyroidism and sodium thiosulfate to improve the calcification of the arterioles. Two months after the start of the therapy, parathyroid hormone (PTH) decreased significantly and the skin lesions nearly disappeared. Thus, we believe that the combination of sodium thiosulfate with cinacalcet and paracalcitol is effective for the treatment of calciphylaxis with secondary hyperparathyroidism.

Osmolality is an expression of the number of particles in a given weight of solvent (mOsm). Measured osmolality is determined by the osmometer, and calculated osmolality is estimated by 2xNa + UN/2.8 + glucose/18. The difference between measured and calculated osmolality is the osmolal gap. The purpose of the present study is to determine the measured and the calculated osmolality and the osmolal gap in hemodialyzed uremic patients, pre- and post-hemodialysis (HD). In 24 uremic patients under regular HD, blood samples pre- and post-HD were collected, and serum osmolality measured (osmometer) and calculated (2xNa + UN/2.8 + glucose/18) and the osmolal gap (measured-calculated osmolality) were determined. Also, the same parameters were determined in 22 healthy subjects (control). According to our findings, the measured osmolality in patients is significantly higher pre- and post-HD in comparison to that of controls, but post-HD is significantly lower than pre-HD. Also, calculated osmolality is significantly higher pre- and post-HD in comparison to that of controls, but the value post-HD is significantly lower than the pre-HD. The osmolal gap of patients pre-HD (11 ± 2.08) and post-HD (7.29 ± 1.94) is significantly higher (P < 0.001) in comparison to that of controls (3.18 ± 1.46); also, the value post-HD is significantly decreased in comparison to the value pre-HD (P < 0.001). Uremic hemodialyzed patients present high measured and calculated osmolality pre-HD that remains high post-HD in comparison to that of controls in spite of the significant decrease post-HD in comparison to that of pre-HD. Also, the osmolal gap is high pre-HD and, in spite of the decrease, remains high post-HD. In comparison to that of controls, the high osmolal gap indirectly indicates the presence of unidentified endogenous osmoles in the serum of uremic patients which partly are removed during HD.

The aim of this retrospective study was to evaluate the International Normalized Ratio (INR) in hemodialyzed uremic patients under treatment with oral anticoagulation drugs. Eleven out of one hundred and forty-two uremic hemodialyzed patients in our unit were included in the study. These 11 patients aged from 70 to 85 (mean: 76 years) were under oral anticoagulation treatment for protection from thromboembolic events. They received 1 mg acenocumarol daily with the therapeutic goal of achieving an INR between 2 and 2.5 units. During the last year, the number of total INR determinations was 129. Based on the INR levels, measurements were classified into three categories of anticoagulation, termed “under-anticoagulation”, “target-anticoagulation”, and “over-anticoagulation”. The number, the percentage, and the mean value (±SD) of INR measurements for each category, respectively, were under-anticoagulation: 39, 30%, 1.78 ± 0.14; target-anticoagulation: 48, 37.5%, 2.20 ±0.14; and over-anticoagulation: 42, 32.5%, 3.14 ± 0.64. The mean value ±SD of all INR determinations (n=129) was 2.34 ±0.65. No thromboembolic or major bleeding events occurred in our patients with these INR. In conclusion, in elderly, hemodialyzed uremic patients with indications for oral anticoagulation treatment, adequate and safe INR levels can be achieved in a high proportion without serious deviations from the therapeutic goal by using low doses of drugs. Therefore, oral anticoagulation therapy should not be considered automatically contra-indicated in this patient group.

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.

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