Background and objectives: Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.Design, setting, participants, & measurements: Hemodialysis patients with phosphorus levels >5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met.Results: Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were >80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl).Conclusions: In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated.

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Background/Aims: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO₃) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. Methods: We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO₃ or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results: There were no statistically significant differences between LaCO₃ and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO₃. Conclusion: Twelve months of LaCO₃ had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

Background/Aims: Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods: We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters^2.7 (LVM/Ht^2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). Results: Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht^2.7 increased (47 ± 13 vs. 53 ± 13 g/m^2.7, p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht^2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht^2.7 (r² = 0.582, p = 0.03). Conclusion: Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers.

Spearman correlation demonstrated moderate to strong correlation between self-assessments completed alone (no simultaneous peer assessment) and self-assessments completed at the time of peer assessments (ρ = .59, p < .0001) but weak correlation between the two self-assessments and peer assessments (alone: ρ = .13, p < .013; at time of peer: ρ = .21, p < .0001). Generalized estimating equation models revealed that self-assessments done alone (p < .0001) were a significant predictor of self-assessments done at the time of peer. Course was also a significant predictor (p = .01) of self-assessment scores done at the time of peer. Peer assessment score was not a significant predictor. Bhapkar's test revealed subgroup membership based on the relationship between self- and peer ratings was relatively stable across Time 1 and Time 2 assessments (χ = 0.83, p = .84) for all but one subgroup; members of the subgroup with initially high self-assessment and low peer assessment were significantly more likely to move to a new classification at the second measurement. A missing data analysis revealed that students who completed all self-assessments had significantly higher average peer assessment ratings compared to students who completed one or no self-assessments with a difference of -0.32, 95% confidence interval [-0.48, -0.15]. Insights: Multiple measurements of simultaneous self- and peer assessment identified a subgroup of students who consistently rated themselves higher on professionalism attributes relative to the low ratings given by their peers. This subgroup of preclinical students, along with those who elected to not complete self-assessments, may be at risk for professionalism concerns. Use of this multisource feedback tool to measure perceptual stability of professionalism behaviors is a new approach that may assist with early identification of at-risk students during preclinical years.