ABSTRACT
BACKGROUND: Hyperphosphatemia is a common complication of late-stage chronic kidney disease (CKD). Nicotinamide (NAM) has been reported as an adjunctive therapy for hyperphosphatasemia, but the effect of NAM on fibroblast growth factor 23 (FGF23) and Klotho has rarely been reported. METHODS: We randomly assigned 98 patients who underwent regular hemodialysis to received NAM (0.5-1.5 g per day, or 1-3 tablets per day) or placebo (1-3 tablets per day) as an add-on therapy of calcium-based phosphorus binders in a 1:1 ratio. All enrollments were followed-up for 52 weeks. We investigated the serum phosphorus as the primary outcome and serum FGF23 and Klotho as the secondary outcomes. Abdominal aortic calcification (AAC), which had a good correlation with coronary calcification was also compared between the two groups. RESULTS: In total, 37 patients in the placebo group and 35 patients in the NAM group completed the 52-week follow-up. Compared with the placebo group, the NAM group showed a significant decrease of serum phosphorus at the 8th, 12th, 20th, 44th, and 52nd week. There was a declining trend of FGF23 and Klotho in both the placebo and NAM groups. Linear mixed models (LMMs) for overall comparisons by repeated measures of analysis of variance (ANOVA) revealed a significant decrease of FGF23 and slower declining rate of Klotho in the NAM group. No significant difference of AAC was detected between the two groups (P=0.805). CONCLUSIONS: NAM can not only further decrease the phosphorus level but also reduce the FGF23 level and slow down the descending rate of Klotho in chronic hemodialysis patients.
ABSTRACT
OBJECTIVE: To explore the effect of renal replacement therapy (RRT) on the plasma drug concentration of first-line antituberculosis drugs. METHODS: Thirty patients treated with continuous RRT and who were complicated with pulmonary tuberculosis from 2009 September to 2013 September were enrolled in the study. There were 19 males and 11 females, aged 18-75 years. They received RRT 3 times a week, 4 h each. The patients took isoniazid 300 mg and rifampin 450 mg one time every day, and pyrazinamide 40 mg · kg(-1) · d (-1) one time 24 h before RRT, 3 times every week. The plasma concentration of the drugs were monitored before and after each RRT for 4 weeks. RESULTS: Taken before RRT, the plasma concentration of isoniazid before RRP was (1.62 ± 0.44), (1.67 ± 0.38), (1.63 ± 0.41), (1.48 ± 0.38) mg/L respectively for 1-4 weeks; while that after RRT was (0.57 ± 0.22), (0.60 ± 0.24), (0.56 ± 0.20), (0.56 ± 0.15) mg/L (all P < 0.05). Taken before RRT, the plasma concentration of pyrazinamide before RRT was (16.08 ± 4.95), (16.32 ± 5.73), (14.89 ± 4.53), (13.81 ± 5.83) mg/L respectively for 1-4 weeks, while that after RRT was (3.73 ± 1.57), (3.57 ± 1.53), (3.22 ± 1.00), (2.81 ± 1.34) mg/L (all P < 0.05). Taken after RRT at once, the plasma concentration of pyrazinamide before RRT was (15.57 ± 3.47), (14.10 ± 2.27), (14.73 ± 2.36), (15.9 ± 3.02) mg/L respectively for 1-4 weeks, while that after RRT was (2.45 ± 1.14), (2.19 ± 1.07), (1.87 ± 1.52), (2.33 ± 1.30)mg/L. Taken before RRT, the plasma concentration of rifampin was (3.44 ± 1.17), (3.72 ± 1.24), (3.68 ± 1.16), (3.44 ± 1.22) mg/L respectively for 1-4 weeks (all P < 0.05), while that after RRT was (2.96 ± 1.10), (3.28 ± 1.04), (3.17 ± 1.02), (2.96 ± 1.05) mg/L (all P > 0.05). CONCLUSIONS: Continuous RRT has different effects on the plasma drug concentration of isoniazid and pyrazinamide. It almost has no effect on rifampin. To achieve the best plasma concentration and better anti-tuberculosis results, isoniazid and pyrazinamide should be taken after RRT, but rifampin before RRT.
