The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients.

BACKGROUND: Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. METHODS: An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. RESULTS: 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 +/- 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 +/- 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant (p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. CONCLUSION: Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885].

A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients.

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 > or =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 > or =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.

Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients.

BACKGROUND: Vitamin D deficiency is common in CKD and dialysis patients. Studies suggest a physiologic autocrine and/or paracrine role for 1,25(OH)D produced via 1alpha-hydroxylase in tissues such as vascular smooth muscle, breast, prostate, and bone marrow. Studies have not yet defined the optimal dose and duration of vitamin D necessary to replete and maintain stores in dialysis patients, or whether it is safe or beneficial. METHODS: We performed a review of the prevalence of vitamin D deficiency and the safety and effectiveness of ergocalciferol oral supplementation (vitamin D(2), 50,000 IU monthly) given to hemodialysis patients during dialysis May to October 2005 in St. Louis (latitude 38 degrees ). RESULTS: Among the 119-patient cohort present for the entire 6 months, 25(OH)D was (mean +/- SD) 16.9 +/- 8.5 ng/ml, (91% < 30 ng/ml) and increased to 53.6 +/- 16.3 ng/ml (p < 0.001), (95% > 30 ng/ml, and none > 100 ng/ml). Initial versus 6 mo. serum calcium (9.1 +/- 0.56 vs. 9.2 +/- 0.70), phosphorus (5.25 +/- 1.38 vs. 5.11 +/- 1.31), Ca x P, and paricalcitol dose (10.3 +/- 9.6 vs. 11.3 +/- 9.2 mcg/week) were not significantly different. No hypercalcemia could be attributed to supplementation. Mean hemoglobin did not change significantly (11.96 +/- 1.4 vs. 11.69 +/- 1.4, p = 0.124), but most patients experienced a reduced weekly epoetin dose. Epoetin dose decreased in 64% of patients, and increased in 28%. CONCLUSIONS: We conclude that the vast majority of hemodialysis patients are vitamin D-deficient; monthly ergocalciferol 50,000 IU is safe and effective in normalizing serum 25(OH)D levels and may have an epoetin-sparing effect.

Prevalence of the metabolic syndrome in an incident dialysis population.

The National Heart, Lung, and Blood Institute's National Cholesterol Education Program 2001 Adult Treatment Panel III report defined the metabolic syndrome as having at least 3 of the following 5 criteria: abdominal obesity, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, an elevated blood pressure, and an elevated fasting glucose. Evidence is accumulating to suggest that the metabolic syndrome predisposes to cardiovascular disease (CVD). End-stage kidney disease (ESKD) patients requiring dialysis have a substantially elevated risk of CVD morbidity and mortality. Dialysis patients' increased risk can be partially explained by traditional and nontraditional risk factors. The prevalence of the metabolic syndrome in dialysis patients is unknown. This retrospective, cross-sectional study of 202 incident dialysis patients examined the prevalence of the metabolic syndrome at the time of renal replacement therapy initiation. The study group was compared with all incident dialysis patients in 2002 on file with the U.S. Renal Data System. Females represented 39.1% of the study population. Blacks composed 34.7% of the study group. Diabetes was the etiology of ESKD in 44.6% of our patients. Surrogate criteria were used for the Adult Treatment Panel III risk factors of abdominal obesity and elevated fasting glucose levels. Overall, the prevalence of the metabolic syndrome was 69.3% in our population and was especially prevalent among diabetic, female, and white ESKD patients. Study limitations included the use of surrogate markers for 2 criteria of the metabolic syndrome and dependence on the Medical Evidence Report (Form 2728) for baseline characteristics. In summary, the metabolic syndrome is highly prevalent in incident dialysis patients.

Personal digital assistant-based drug information sources: potential to improve medication safety.

OBJECTIVES: This study compared the potential for personal digital assistant (PDA)-based drug information sources to minimize potential medication errors dependent on accurate and complete drug information at the point of care. METHODS: A quality and safety framework for drug information resources was developed to evaluate 11 PDA-based drug information sources. Three drug information sources met the criteria of the framework: Eprocrates Rx Pro, Lexi-Drugs, and mobileMICROMEDEX. Medication error types related to drug information at the point of care were then determined. Forty-seven questions were developed to test the potential of the sources to prevent these error types. Pharmacists and physician experts from Creighton University created these questions based on the most common types of questions asked by primary care providers. Three physicians evaluated the drug information sources, rating the source for each question: 1=no information available, 2=some information available, or 3 = adequate amount of information available. RESULTS: The mean ratings for the drug information sources were: 2.0 (Eprocrates Rx Pro), 2.5 (Lexi-Drugs), and 2.03 (mobileMICROMEDEX). Lexi-Drugs was significantly better (mobileMICROMEDEX t test; P=0.05; Eprocrates Rx Pro t test; P=0.01). CONCLUSION: Lexi-Drugs was found to be the most specific and complete PDA resource available to optimize medication safety by reducing potential errors associated with drug information. No resource was sufficient to address the patient safety information needs for all cases.