Table 2.

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

Potential benefitsPotential 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 
Potential benefitsPotential 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.

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