Abstract

Background and Aims

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) patients that serves as the main risk factor of CKD–mineral and bone disorder (CKD-MBD) progression. Previous studies suggested that iron-based phosphate binder showed better improvement in CKD-MBD parameters although the results were still inconclusive. This study aims to juxtapose the efficacies between iron-based and non-calcium phosphate binders for improving CKD-MBD parameters in dialysis-dependent (DD)-CKD patients.

Method

We did comprehensive searching to screen all relevant literature until November 2020 in online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library. We included all randomized controlled trials (RCTs) accessing the efficacies of iron-based phosphate binders (sucroferric oxyhydroxide, ferric citrate) in improving CKD-MBD parameters compared with non-calcium phosphate binders (sevelamer) in DD-CKD patients. The parameters compared in this study are changes in serum phosphate (P), serum calcium ions (Ca), fibroblast growth factors-23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (calcidiol), and 1,25-dihydroxyvitamin D (calcitriol). Bias risk was accessed by using the revised Cochrane Risk-of-bias (RoB-2) tool. Analysis was performed to provide standard mean difference (SMD) with 95% confidence interval (CI) using random-effect heterogeneity test.

Results

Ten RCTs with total of 1,139 participants were included in this analysis. The sucroferric oxyhydroxide decreases FGF23 although not statistically significant (SMD = 0.22. 95% CI = -0.49 to 0.05, p = 0.11, I2 = 52%), but ferric citrate (SMD = -0.92. 95%CI = -1.56 to -0.29, p = 0.004, I2 = 69%) and the overall estimate (SMD = -0.45. 95% CI = -0.82 to -0.09, p = 0.02, I2 = 79%) showed significant FGF23 decline compared with sevelamer. The sucroferric oxyhydroxide showed no significant improvement of calcidiol (SMD = 0.08. 95%CI = -0.02 to 0.17, p = 0.13, I2 = 0%) and calcitriol (SMD = 0.02. 95% CI = -0.08 to 0.12, p = 0.74, I2 = 0%) compared with selevamer. There is also no significant improvement of iPTH in sucroferric oxyhydroxide subgroup (SMD = -0.14. 95%CI = -0.43 to 0.14, p = 0.32, I2 = 85%), ferric citrate subgroup (SMD = -0.02. 95%CI = -0.16 to 0.12, p = 0.80, I2 = 0%), and pooled group analysis (SMD = -0.10. 95%CI = -0.27 to 0.07, p = 0.27, I2 = 75%). Besides, this study also suggests no significant improvement comparison of serum P (SMD = -0.09. 95%CI = -0.19 to 0.02, p = 0.12, I2 = 38%) and Ca (SMD = 0.04. 95%CI = -0.12 to 0.20, p = 0.61, I2 = 57%).

Conclusion

There is no significant efficacies differences between iron-based and non-calcium phosphate binders for improving serum phosphate, serum calcium ions, iPTH, calcidiol, and calcitriol in dialysis-dependent chronic kidney disease patients, except for the FGF-23 parameter. However, further trials are needed to establish the juxtaposition.

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