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.

Frequency and Risk Factors of Kidney Alterations in Children and Adolescents who Are Overweight and Obese in a Primary Health-care Setting.

OBJECTIVE: Obesity is clearly associated to kidney disease in adult population; however, there is scarce evidence in children and adolescents. The aim was to compare frequency of renal damage according to the presence of overweight-obesity in children and adolescents, as well as to compare nutritional and biochemical risk factors, according to the presence of kidney alterations. METHODS: Cross-sectional study; 172 children and adolescents, 6-16 years old, without malnutrition, diabetes mellitus, hypertension and independent comorbid conditions associated to obesity or kidney disease, as well as transitory causes of microalbuminuria (MA) from a Primary Health-Care Unit were included. Clinical, biochemical, anthropometric and dietetic evaluations were measured in all subjects; subsequently they were classified as normal weight, overweight and obesity groups according to sex- and age-adjusted body mass index (BMI). Glomerular filtration rate (GFR, estimated by Schwartz equation) and albuminuria (albumin/creatinine ratio) were determined. Presence of kidney alterations was measured as decreased GFR (<90 mL/min/1.73m2), hyperfiltration (>170 mL/min/1.73m2) and MA (30-300 mg/g). RESULTS: Compared with controls, subjects with overweight-obesity had significantly (P<.05) abdominal obesity (0 vs 69%), hypertension (19 vs 26%), hypertriglyceridemia (11 vs 47%), high low-density lipoprotein cholesterol (2 vs 8%) and low high-density lipoprotein cholesterol (HDL-cholesterol; 2 vs 28%), hyperuricemia (11 vs 28%) and hyperinsulinemia (8 vs 70%). Hyperfiltration and MA were present in 5 and 4 subjects with overweight/obesity, respectively, whereas decreased GFR was present in only 1 subject with obesity. Normal weight subjects had no kidney alterations. In multivariate analysis, kidney alterations were significantly predicted by higher BMI and lower HDL-cholesterol. CONCLUSIONS: Kidney alterations were observed only in subjects with overweight (3.6%) and obesity (9.9%), who additionally, displayed cardiometabolic and kidney disease risk factors more frequently than normal weight subjects.

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.