Ascorbic Acid for Anemia Management in Hemodialysis Patients: A Systematic Review and Meta-analysis

Background: Ascorbic acid is believed to improve anemia in patients with end-stage renal disease, but its overall effectiveness is unclear. Study Design: Systematic review and meta-analysis. Setting & Population: Adult hemodialysis patients. Selection Criteria for Studies: Randomized clinical trials of ascorbic acid use in addition to standard anemia management. Intervention: Ascorbic acid. Outcomes: Weighted mean difference (WMD) for change in hemoglobin level, recombinant human erythropoietin (rHuEPO) dose, transferrin saturation and ferritin level and adverse events. Results: Of 157 potentially relevant studies, 6 studies (n = 326 patients) met the inclusion criteria. Combining the 3 randomized clinical trials involving patients with baseline hemoglobin levels < 11 g/dL, change in hemoglobin level was greater for ascorbic acid use compared with standard care (WMD, 0.9 g/dL; 95% Cl, 0.5-1.2 g/dL). Compared with standard care, ascorbic acid use also was associated with a statistically significant decrease in rHuEPO dose (WMD, -17.1 U/kg/wk; 95% Cl, -26.0 to -8.2 U/kg/wk) and improvement in transferrin saturation (WMD, 7.9%; 95% Cl, 5.2-10.5%), with no change in ferritin concentration. Adverse events had questionable relevance to ascorbic acid use; no study reported oxalate levels or occurrence of oxalosis. Limitations: Small number of studies, heterogeneity between study populations, and study durations were short. Adverse events were poorly reported. Conclusions: Although the studies are limited by small numbers of subjects, short durations of follow-up, and variable quality, these results suggest that compared with standard care, ascorbic acid use may result in an increase in hemoglobin concentration and transferrin saturation and decrease in rHuEPO requirements. Longer term studies are required to confirm these results, provide information about adverse events, and determine whether these changes translate into improved patient outcomes and cost-effectiveness. Am J Kidney Dis 54:1089-1097. (C) 2009 by the National Kidney Foundation, Inc.