Randomized, double-blinded, controlled clinical trial of the effect of captopril, telmisartan and their combination on systemic inflammation of patients on hemodialysis.

To evaluate individual and combined effect of captopril and telmisartan on systemic inflammation markers of hemodialysis (HD) patients. Randomized, double-blinded, controlled clinical trial. Patients on HD at least 2 months, with arteriovenous fistula, were randomly allocated to groups: (1) captopril/placebo (N 13); (2) telmisartan/placebo (N 13); (3) captopril + telmisartan (N 12); or (4) placebo/placebo (N 12). During 3 months, patients received oral drugs as follows: captopril 50 mg/day, telmisartan 80 mg/day or placebo. Patients excluded if they had conditions or were on drugs potentially influencing on inflammation. Clinical and biochemical evaluations were performed monthly. Serum tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured at 0, 1 and 3 months. Baseline, demographic, clinical and biochemical variables were comparable between groups. Baseline versus final inflammatory markers were: captopril/placebo TNFα, 2.47 (0.1-4.5) versus 1.73 (0.3-3.8) pg/ml; IL-6, 17.03 (7.2-23) versus 7.90 (0.7-19) pg/ml; CRP, 4.21 (1.6-18) versus 5.9 (3.0-28) mg/l; telmisartan/placebo TNFα, 3.03 (2.3-4.6) versus 1.70 (1.2-2.0) pg/ml; IL-6, 14.10 (5.5-23) versus 9.85 (6.2-13) pg/ml; CRP, 5.74 (2.1-13) versus 10.60 (1.5-27) mg/l; captopril + telmisartan TNFα, 1.43 (0.7-5.4) versus 0.40 (0.1-2.1) pg/ml; IL-6, 10.05 (4.9-23) versus 4.00 (0.7-7.7) pg/ml (p < 0.05); CRP, 3.26 (0.7-12) versus 2.83 (0.6-6.5) mg/l; placebo/placebo TNFα, 3.13 (1.6-5.6) versus 1.64 (1.6-2.3) pg/ml; IL-6, 8.12 (5.4-16) versus 7.60 (2.4-15) pg/ml; CRP, 5.23 (1.9-16) versus 3.13 (1.5-18) mg/l. Monotherapy with captopril or telmisartan display a trend, but their combined treatment significantly decreased serum levels of IL-6. No remarkable changes on TNFα and CRP were observed.

Soluble Triggering Receptor on Myeloid Cell-1 and its Predictive Factors in Patients With End-Stage Kidney Disease on Hemodialysis.

Triggering receptor expressed on myeloid cells (TREM)-1 is a potent and early amplifier of the inflammatory response expressed on neutrophils and monocytes/macrophages. TREM-1, and its soluble form (sTREM-1), are increased in sepsis and other noninfectious inflammatory conditions. However, virtually no data are available in kidney disease. To determine serum sTREM-1 and its associated variables in patients on hemodialysis (HD), cross-sectional study including 264 HD patients and 148 controls. sTREM-1 was measured by quantitative sandwich enzyme immunoassay; soluble tumor necrosis factor receptor-1 (sTNF-R1), interleukin-6 (IL-6), and C-reactive protein (CRP) were also measured. All inflammation markers were significantly higher in HD patients than controls. Median (IQR) sTREM-1 was 1,006 (613-1,650) pg/mL but undetectable in controls. Considering only HD patients, sTREM-1 was positively correlated with IL-6 (r = 0.19, p = 0.008), and its levels were significantly higher in patients with arteriovenous fistula than in those with temporary catheter (1,226 vs. 743 pg/mL), in patients with 3 HD sessions/week than in those with 2 sessions/week (1,150 vs. 646 pg/mL), and in patients with >1 year on HD than in those with ≤1 year (1,100 vs. 948 pg/mL), whereas they were not different regarding age or presence of infection. Serum sTREM-1, sTNF-R1, IL-6, and CRP were higher in HD patients compared to controls. In HD patients, sTREM-1 displayed higher levels in individuals with arteriovenous fistula, 3 sessions/week and longer vintage, but not in those with infection or older age; in multivariate analysis, only the first two variables significantly predicted higher sTREM-1 levels.

Vascular calcification in Mexican hemodialysis patients.

BACKGROUND AND AIMS: Vascular calcification (VC) is a predictor of poor survival and cardiovascular outcome in end-stage renal disease (ESRD) patients; however, there is scarce information of VC in Latin America, and virtually no data in our setting. We undertook this study to evaluate the prevalence and characteristics of VC in a hemodialysis (HD) population from western Mexico and to determine possible associated factors. METHODS: This was a cross-sectional study performed in 52 patients. VC was evaluated using plain X-ray films (Adragao's score) of hands and pelvis; clinical and biochemical variables were also collected. Statistical analysis was carried out with Student t and χ(2) tests performed as appropriate and logistic regression to determine predictors of VC. RESULTS: Mean age was 43 years, 48% were female, 23% had diabetes mellitus (DM), and median time on dialysis was 46 months. Percentage prevalence was 52% with a mean calcification score of 2.0 ± 2.6; 23% of patients had severe calcification. VC was present in about 23-37% among the different vascular territories evaluated (radial, digital, femoral and iliac). Patients with calcification were significantly older, had a higher frequency of DM, higher alkaline phosphatase and lower HDL lipoproteins than those without VC. In the multivariate analysis, VC in these patients was significantly predicted only by an older age (OR [95% CI]: 1.15 [1.01-1.31], p = 0.04); lower HDL-cholesterol and higher alkaline phosphatase were marginal predictors. CONCLUSIONS: Half of our HD patients had VC. Territories of radial, iliac, femoral and digital arteries were roughly equally affected, and 25% of patients had a calcification considered as severe. Older age was the only significant predicting variable for VC, with low HDL-cholesterol and high alkaline phosphatase as marginal predictors.

Is systemic inflammation of hemodialysis patients improved with the use of enalapril? Results of a randomized, double-blinded, placebo-controlled clinical trial.

This study compared the effect of enalapril versus placebo on serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C-reactive protein (CRP) in hemodialysis in a randomized, double- blinded, controlled clinical trial. Patients without infection or antiinflammatory drugs were randomly allocated to a study (n = 13, enalapril, 20 mg/day) or control (n = 12, placebo) group; all had arteriovenous fistula. Serum TNF-alpha, IL-6, and CRP were measured at 0, 1, and 3 months. Systolic blood pressure (baseline vs. final) was 151 +/- 25 vs. 135 +/- 19 mm Hg (p < 0.05) in the study group and 154 +/- 21 vs. 144 +/- 27 mm Hg in control group; diastolic blood pressure was 86 +/- 9 vs. 76 +/- 13 and 91 +/- 16 vs. 81 +/- 18 mm Hg, respectively; median (percentiles 25%-75%) IL-6 (baseline vs. final) was 4.2 (3-8) vs. 4.1 (2-9) pg/mL and 6.3 (3-9) vs. 6.7 (3-8) pg/mL; and CRP was 1.9 (1-7) vs. 3.0 (1-12) mg/L and 4.7 (1-16) vs. 3.9 (2-16) mg/L, respectively. TNF-alpha was detected in only two patients. Enalapril significantly reduced blood pressure in hemodialysis patients, but it did not decrease IL-6 and CRP compared with placebo.