In a study of 155,974 adult enrolleesin the Kaiser Permanente SouthernCalifornia health system, each 0.5 mg/dL increment in serum phosphoruslevel was associated with a significant16% increased risk for moderate anemia.Patients in the highest tertile ofserum phosphorus had a significant26% increased likelihood of moderateanemia than those in the middle tertile,Lac Tran, MD, of Kaiser PermanenteLos Angeles Medical Center, and colleaguesreported online ahead of printin Nephrology Dialysis Transplantation.
Of the 155,974 subjects, 4.1% hadmoderate anemia and 12.9% had mildanemia. The investigators defined moderateanemia as a hemoglobin level below11 g/dL for both sexes and mild anemiaas a hemoglobin level below 12 g/dL inwomen and less than 13 g/dL in men.
“Our study is one of the largest, ethnicallydiverse, non-dialysis populationsto date evaluating the associationbetween phosphorus and anemia,”Dr. Tran told Renal & Urology News.“Unlike prior studies, we had comprehensiveinformation on co-morbiditiesand laboratory [parameters] thatenabled us to adjust for potential confoundersand exclude many secondarycauses of anemia.”
Theoretically, based on the new findings,if 87 individuals were treated tolower their phosphorus levels from4.0 to 3.5 mg/dL, one excess case ofmoderateanemia could be prevented,Dr. Tran noted. This implies that loweringphosphorus within the studypopulation by 0.5 mg/dL could correlatewith prevention of anemia inhundreds of individuals, he said. “Thisis important because anemia itself hasalready been associated with adverseoutcomes, including higher incidencesof coronary events, stroke, and progressionto renal failure.”
The study identified female sex, Asianrace, diabetes, low albumin, and lowiron saturation as other independentanemia risk factors. In addition, thestudy showed that each 10-unit increasein estimated glomerular filtration ratewas associated with a 6% decrease inthe risk of moderate anemia.
The researchers stated that fibroblastgrowth factor 23 (FGF-23) may have arole in the mechanism underlying theassociation between hyperphosphatemiaand anemia. High phosphorus levelshave been shown to increase FGF-23levels, which in turn is associated withklotho suppression, they explained. Inanimal studies, low klotho levels havebeen associated with poor outcomes. Inaddition, low klotho causes a deficiencyin activated vitamin D, and vitamin Ddeficiency has been implicated in thedevelopment of anemia.
Dr. Tran’s group acknowledged somestudy limitations. The information forthe study came from a real-world clinicalpractice environment. “Thus, thereis a bias toward those individuals whohad indications for concurrent hemoglobin,creatinine and phosphorusvalues to be drawn. This cohort mayrepresent a sicker population withunhealthy lifestyles who sought medicalcare.”
Another limitation was a lack ofinformation about medication useamong cohort members. “The use ofmedications such as phosphorus binders,erythropoietin, steroids or ironsalts was not ascertained. Among CKDpatients, certain phosphorus bindershave been associated with improvedanemia parameters.”