Table 2.

Risk and benefit considerations for use of HIF-PHIs in patients with CKD

Potential benefits	Potential disadvantages including theoretical risks
Oral dosing for patients not on dialysis (indication not yet approved in United States), patients on home HD or peritoneal dialysis	In NDD-CKD cardiovascular safety trials, lack of non-inferiority compared to ESAs (dependent on type of analysis and geographical location)
No cold storage needed	Potential drug-drug interactions due to polypharmacy
Beneficial effects on iron metabolism (absorption and utilization)	Increased pill burden, potential for error due to different strength pills and overdosing, narrow therapeutic window
Effective in patients with chronic inflammationa	Difficult compliance monitoring
Potential cytoprotective effects	Risk of promoting malignancy or kidney cyst growth
	Risk of promoting proliferative retinopathy
	Risk of promoting pulmonary arterial hypertension
	Lack of studies on use in children and patients post renal transplantation

^a It is unclear whether HIF-PHIs are more effective in patients with inflammation at the recommended dose levels; further studies are pending.

NDD, non–dialysis-dependent.