Prevalence, predictors, and natural history of hypophosphatemia following iron infusion

Iron deficiency is the leading cause of anemia, which affects 1 quarter of the adult population globally. Intravenous iron is a well-established treatment option and is generally well tolerated. However, there is increasing recognition that it can cause hypophosphatemia, which can result in fatigue, nausea, myalgia, weakness, and osteomalacia. We sought to determine the prevalence, natural history, and predictors of hypophosphatemia following iron infusion in a tertiary hospital. All adult patients who received 1 or more iron infusions between January 1, 2019 and December 31, 2021 were included in this retrospective study. A total of 2367 subjects were identified, receiving a total of 7063 infusions over the study period. Hypophosphatemia was defined as a serum phosphate level of <0.75 mmol/L (<2.32 mg/dL), with severity classified as mild 0.65-0.75 mmol/L (2.01-2.31 mg/dL), moderate 0.32-0.64 mmol/L (0.99-1.98 mg/dL), or severe <0.32 mmol/L (<0.99 mg/dL). Prevalence of hypophosphatemia was 48.9%, with the highest prevalence from day 4 to 20 post-iron infusion (39.3%-44.1%). Risk factors were receipt of iron polymaltose (odds ratio [OR] 2.33, CI 1.71-3.19, p < .0001), receipt of ferric carboxymaltose (OR 1.79, CI 1.29-2.48, p = .001), male gender (OR 1.35, CI 1.09-1.66, p = .006), and multiple iron infusions (OR 1.56, CI 1.20-2.03, p = .001). Risk was reduced in recipients with higher baseline phosphate (OR 0.18, CI 0.11-0.28, p < .0001), higher baseline creatinine (OR 0.83, CI 0.74-0.92, p = .001), and increased weight (OR 0.99, CI 0.99-1.00, p = .016). Risk factors for moderate to severe hypophosphatemia were the same, except that gender became nonsignificant, while increasing age (OR 0.99, CI 0.99-1.00, p = .002) was also associated with reduced risk. These findings may aid clinicians in identifying those at greatest risk of developing significant hypophosphatemia, thereby preventing adverse outcomes.