Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.

BACKGROUND AND OBJECTIVES: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. RESULTS: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. CONCLUSIONS: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

Sensitivity of International Classification of Diseases codes for hyponatremia among commercially insured outpatients in the United States.

BACKGROUND: Administrative claims are a rich source of information for epidemiological and health services research; however, the ability to accurately capture specific diseases or complications using claims data has been debated. In this study, the authors examined the validity of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for the identification of hyponatremia in an outpatient managed care population. METHODS: We analyzed outpatient laboratory and professional claims for patients aged 18 years and older in the National Managed Care Benchmark Database from Integrated Healthcare Information Services. We obtained all claims for outpatient serum sodium laboratory tests performed in 2004 and 2005, and all outpatient professional claims with a primary or secondary ICD-9-CM diagnosis code of hyponatremia (276.1). RESULTS: A total of 40,668 outpatient serum sodium laboratory results were identified as hyponatremic (serum sodium < 136 mmol/L). The sensitivity of ICD-9-CM codes for hyponatremia in outpatient professional claims within 15 days before or after the laboratory date was 3.5%. Even for severe cases (serum sodium < or = 125 mmol/L), sensitivity was < 30%. Specificity was > 99% for all cutoff points. CONCLUSION: ICD-9-CM codes in administrative data are insufficient to identify hyponatremia in an outpatient population.

Medical costs of abnormal serum sodium levels.

An abnormal serum sodium level is the most common electrolyte disorder in the United States and can have a significant impact on morbidity and mortality. The direct medical costs of abnormal serum sodium levels are not well understood. The impact of hyponatremia and hypernatremia on 6-mo and 1-yr direct medical costs was examined by analyzing data from the Integrated HealthCare Information Services National Managed Care Benchmark Database. During the period analyzed, there were 1274 patients (0.8%) with hyponatremia (serum sodium <135 mmol/L), 162,829 (97.3%) with normal serum sodium levels, and 3196 (1.9%) with hypernatremia (>145 mmol/L). Controlling for age, sex, region, and comorbidities, hyponatremia was a significant independent predictor of costs at 6 mo (41.2% increase in costs; 95% confidence interval, 30.3% to 53.0%) and at 1 yr (45.7% increase; 95% confidence interval, 34.2% to 58.2%). Costs associated with hypernatremia were not significantly different from those incurred by patients with normal serum sodium. In conclusion, hyponatremia is a significant independent predictor of 6-mo and 1-yr direct medical costs.

Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined. METHODS: We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders. RESULTS: During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n=77) tended to be younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89-13.76). CONCLUSIONS: Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.