The Effect of Iron Supplementation on FGF23 in Chronic Kidney Disease Patients: a Systematic Review and Time-Response Meta-Analysis.

Abstract

Fibroblast growth factor 23 (FGF23) gene is found to be responsible for autosomal dominant hypophosphatemic rickets, and is highly expressed in chronic kidney disease (CKD) and end-stage renal disease patients with iron deficiency anemia (IDA). We evaluated the efficacy of different iron treatments on FGF23 levels in dialysis-dependent and non-dialysis-dependent CKD patients with IDA. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing different types of iron treatment versus placebo in CKD patients up to May 2020. We investigated the efficacy of iron treatment on the levels of FGF23 and C-terminal FGF23 (cFGF23) in CKD patients. We estimated weighted mean differences (WMDs) and 95% confidence intervals (CIs) using the random-effects model. Nine studies with 11 arms were included in the meta-analysis. Overall, iron treatment showed a significant reduction in FGF23 levels compared to control group (WMD: -\u200960.56\xa0pg/ml, 95% CI: -\u200992.17, -\u200928.95). Compared to placebo, subgroup analysis showed that oral iron therapy (WMD: -\u20096.98\xa0pg/ml, 95% CI: -\u200910.66, -\u20093.31) was more effective than intravenous (IV) iron therapy (WMD: 4.90\xa0pg/ml, 95% CI: -\u200912.03, 21.83) on FGF23 levels. There was no significant change in cFGF23 levels between iron treatment and control group (WMD: -\u200964.72 Ru/ml, 95% CI: -\u2009147.69, 18.25). Subgroup analysis showed that oral iron therapy resulted in a significant reduction in cFGF23 levels compared to control group (WMD: -\u2009150.48 RU/ml, 95% CI: -\u2009151.31, -\u2009149.65). In conclusion, iron treatment was associated with a significant decrease in FGF23 levels in CKD patients.