Increasing levels of fibroblast growth factor 23 (FGF23) are independently associated with an elevated risk for incident kidney replacement therapy (KRT), according to investigators.
Rupal Mehta, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, and colleagues used serial FGF23 measurements and FGF23 trajectories to evaluate the association between FGF23 levels and KRT risk among 1597 patients (case-cohort analytic sample) in the Chronic Renal Insufficiency Cohort Study. Patients had up to 5 annual measurements of carboxy-terminal FGF23.
FGF23 regulates phosphate homeostasis by stimulating urinary phosphate excretion and lowering 1,25-dihydroxyvitamin D levels, the investigators noted.
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Of the 1597 patients in the case-cohort analytic sample, 728 reached the KRT outcome and 859 experienced the composite outcome of KRT or death during a median follow-up of 6.3 years.
Each 1 standard deviation increase in mean natural log-transformed FGF23 in the past was significantly associated with a 1.9-fold increased risk for incident KRT (either maintenance dialysis initiation or a kidney transplant) in adjusted analyses, Dr Mehta’s team reported in the American Journal of Kidney Diseases.
The investigators used group-based trajectory modeling for 1163 patients who survived beyond their fifth annual study visit without reaching the KRT outcome. They identified 3 distinct trajectory groups of FGF23 change over time: stable, slowly increasing, and rapidly increasing (mean group slope of 0.03, 0.14, and 0.40 per year, respectively, in natural log-transformed FGF23). Of the 1163 patients, 354 reached the KRT outcome during a median follow-up of 3.2 years.
Compared with a stable FGF23 trajectory, slowly and rapidly increasing FGF23 trajectories were associated with 3.6- and 21.4-fold increased risks for incident KRT, respectively, in fully adjusted models.
Potential mechanisms by which FGF23 increases may lead to CKD progression are not completely understood, but prior research suggests that FGF23 excess may increase fibroblast activation during kidney injury and result in profibrotic signaling, the authors pointed out. FGF23 also might indirectly impact CKD progression by stimulating phosphaturia and promoting nephrocalcinosis, resulting in renal tubular damage and tubulointerstitial fibrosis, they noted.
Dr Mehta and colleagues acknowledged some study limitations, including the possibility of residual confounding and lack of intact FGF23 values.
Reference
Mehta R, Cai X, Lee J, et al. Serial fibroblast growth factor 23 measurements and risk of requirement for kidney replacement therapy: The CRIC (Chronic Renal Insufficiency Cohort) Study [published online December 18, 2019]. Am J Kidney Dis.
