HIF-PHIs for Anemia in Patients Receiving Dialysis

Patients with end-stage renal disease who are receiving maintenance dialysis commonly develop anemia. A new class of small-molecule oral drugs for the treatment of anemia in chronic kidney disease, hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) has emerged recently. The new agents demonstrate advantages of traditional exogeneous erythropoietin (EPO).

Meiyan Wu, MD, and colleagues conducted a meta-analysis of studies comparing the safety and efficacy of HIF-PHI in erythropoiesis and iron metabolism with EPO in patients receiving maintenance dialysis. Results were reported in Clinical and Experimental Nephrology [doi.org/10.007/s10157-022-02263-4].

The researchers utilized a sensitive search strategy to search PubMed, EMBASE, and Cochrane databases to identify all citations for randomized controlled trials comparing HIF-PHI agents with EPO/placebo through December 2021.

A total of 14 randomized controlled trials including 2738 patients were identified. Using the random-effects model, there was no statistically significant difference found in hemoglobin increase (P=.37) between HIF-PHI treatment and EPO treatment. Administration of HIF-PHI upregulated transferrin (mean deviation [MD], 36.12; 95% CI, 27.04-45.20) and soluble transferrin receptors (MD, 1.28; 95% CI, 0.44-2.13), but did not statistically reduce hepcidin level (P=.37).

Total and low density lipoprotein cholesterol levels were suppressed by HIF-PHI (MD, –0.99; 95% CI, –1.34 to –0.63 and MD, –0.99; 95% CI, –1.34 to –0.64, respectively). There was no difference in triglyceride between HIF-PHI and EPO treatment (P=.74).

There were no differences in treatment-emergent adverse events between treatment with HIF-PHI and treatment with erythropoietin. In the fixed-effect model, treatment-emergent serious adverse events were higher in the HIF-PHI group than in those in the EPO controls.

“HIF-PHI could effectively upregulate and maintain hemoglobin levels in patients with anemia receiving maintenance dialysis. Furthermore, HIF-PHI could elevate iron metabolism activity and utility without inducing treatment-associated serious adverse events. Robust data from larger randomized controlled trials with longer treatment duration and follow-up are needed,” the researchers said.