Impact of C-Reactive Protein on HIF-PHIs in Anemia Treatment

Chronic inflammation is common in chronic kidney disease (CKD) and contributes to CKD-related anemia. Inflammation is reflected in a heightened blood C-reactive protein (CRP) level.

In a review published in BMC Nephrology, Xiaoyu Luo and fellow researchers examined the effect of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for treatment of anemia in patients with CKD. The study included data from several electronic databases from their launch through May 19, 2022.

The researchers reviewed evidence from randomized, controlled trials using HIF-PHIs for anemia treatment. A total of seven studies from six publications were included in the meta-analysis. The outcome was mean difference (MD) in changes in hemoglobin concentration before and after treatment.

The team compared a group with CRP levels greater than or equal to the upper limit of normal (CRP ≥ ULN) against a group with levels lower than the ULN (CRP < ULN). They conducted additional analysis in the CRP ≥ ULN group, comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs). In the comparison between the CRP ≥ ULN and CRP < ULN groups, 524 patients from four studies were included in the analysis.

All subjects received roxadustat, and there was no significant difference in hemoglobin concentration in patients with CRP ≥ ULN versus CRP < ULN at baseline (MD, 0.00; 95% CI, −0.32 to 0.33; P=.99). In three studies of 1399 patients in the CRP ≥ ULN group, there was no significant difference in hemoglobin concentration between patients treated with ESAs versus HIF-PHIs (MD, 0.24; 95% CI, −0.08 to 0.56, P=.14). Dosage over time increased for ESAs (particularly in the CRP ≥ ULN group), while the roxadustat dose was consistent.

The authors concluded, “Our systematic review reveals that roxadustat demonstrates consistent efficacy across different CRP levels. Particularly noteworthy is its ability to maintain efficacy comparable [with] ESA in the CRP ≥ ULN group without the need for dose escalation. This finding has implications for advancing research focused on the efficacy of HIF-PHI in patients with CKD experiencing an inflammatory state.”

Source: BMC Nephrology