WASHINGTON—High or low levels of fibroblast growth factor 23 (FGF23) correlate with hyporesponsiveness to erythropoiesis stimulating agents (ESA) in patients on hemodialysis (HD), Tomoko Usui, MD, PhD, of the University of Tokyo in Japan, told attendees of the American Society of Nephrology’s Kidney Week 2019 meeting.

Of 1048 patients from the phase 5 Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS), 144 (13.7%) had mean hemoglobin levels that were less than 10 g/dL despite a standardized mean ESA dose of more than 6000 u/wk for 4 months.

Patients with the highest (median 15,345 pg/mL) and lowest (median 185 pg/mL) quintiles of baseline FGF23 had higher risks of developing ESA hyporesponsiveness, compared with patients in the third quintile (median 2015 pg/mL). The team adjusted for hemoglobin, transferrin saturation, ferritin, creatinine, residual kidney function, parathyroid hormone (PTH) level and cinacalcet use, C-reactive protein, body mass index, Kt/V, treatment time, post-dialysis weight, comorbidities, age, and sex.


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In the quintile 5 group, 14.8% were hyporesponsive to ESAs compared with 10% of quintile 3. Individuals with higher levels of FGF23 tended to be younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, and 25-hydroxyvitamin D. More patients in the higher FGF23 groups also received intravenous iron, vitamin D, and cinacalcet.

In the quintile 1 group, 19.7% (vs 10%) were hyporesponsive to ESAs. Patients with the lowest quintile of FGF23 had higher age and lower BMI, serum albumin, and creatinine.

“This is the first study to examine the association between ESA hyporesponsiveness and FGF23 levels in a relatively large cohort of HD patients,” Dr Usui said. In the quintile 1 group, malnutrition may be suppressing erythropoiesis and FGF23 production, she said. Direct effects of FGF23 may be responsible in patients with the highest levels of FGF23, she said.

“Further understanding of the relationship between FGF23 and anemia may contribute to improved management of anemia in HD patients,” according to Dr Usui.

The DOPPS study is funded by several pharmaceutical companies.

Reference

Usai T, Nangaku M, Zhao J, et al. Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the J-DOPPS study. Presented at the American Society of Nephrology’s Kidney Week 2019 meeting held November 5-10 in Washington DC. Abstract TH-OR030.