Parenteral iron therapy and phosphorus homeostasis: A review

Abstract

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre‐existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

An Expert Perspective on Phosphate Dysregulation With a Focus on Chronic Hypophosphatemia

“…In general, diseases characterized by hypophosphatemia can be divided into those mediated by or independent of FGF23-these may be genetic (hereditary or somatic mosaicism), acquired, or drug-induced (Table 2). (3,11,12,21,(33)(34)(35)(36) In adults, hypophosphatemia can be defined as mild (serum phosphate of 0.6 to 0.8 mmol/L; 1.8 to 2.5 mg/dL), moderate (0.4 to 0.5 mmol/L; 1.0 to 1.7 mg/dL), or severe (serum phosphate <0.3 mmol/L; 0.9 mg/dL); in children, hypophosphatemia is defined based on the age-related normal range (Table 1). (3,37) Hypophosphatemia can also be categorized based on its onset, ie, acute or chronic.…”

“…In general, diseases characterized by hypophosphatemia can be divided into those mediated by or independent of FGF23—these may be genetic (hereditary or somatic mosaicism), acquired, or drug‐induced (Table 2 ). ( 3 , 11 , 12 , 21 , 33 , 34 , 35 , 36 )…”

“…( 3 , 6 , 7 ) Diseases that are characterized by FGF23‐related renal phosphate wasting may be inherited (eg, X‐linked hypophosphatemia [XLH]), caused by somatic mutations (eg, fibrous dysplasia/McCune Albright Syndrome), acquired (eg, tumor‐induced osteomalacia [TIO]), or drug‐induced (eg, intravenous iron supplementation therapy). ( 3 , 8 , 9 , 10 , 11 , 12 ) These rare diseases often remain underrecognized, underdiagnosed, and suboptimally managed. ( 3 ) As such, there is a need for increased awareness and understanding of the causes and consequences of such conditions.…”

Undetected Iatrogenic Drug-Induced Complications in a Hemodialyzed Anuric Patient: A Case Report and Review of the Literature

“…Phosphorus is a ubiquitous ion of the human body widely present in mineralized and soft tissues and to a lesser extent in extracellular fluids where it appears as inorganic phosphate. In adults, normal serum phosphorus levels range from 2.5 mg/dL (0.8 mmol/L) to 4.5 mg/dL (1.45 mmol/L) [ 1 ]. Phosphorus metabolism depends on dietary content, intestinal absorption, plasma pH, phosphatonins such as fibroblast growth factor 23 (FGF23), and circulating levels of parathormone (PTH), calcitriol (1,25[OH]-vitamin D3), glucose, insulin, glucagon, calcitonin, and catecholamines [ 1 , 2 ].…”

“…Phosphate levels are tightly balanced by renal reabsorption through proximal tubule sodium-phosphate cotransporters NaPi2a and NaPi2c [ 3 ], and renal phosphate loss is the main mechanism responsible for hypophosphatemia in the general population [ 1 ]. Severe hypophosphatemia is defined as serum phosphate levels below 1.0 mg/dL (0.32 mmol/L), and these may provoke serious musculoskeletal, neurological, cardiac, and respiratory complications, thus increasing mortality [ 4 ].…”