Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin?

ABSTRACT

Anemia of chronic kidney disease (CKD) is common and is associated with diminished quality of life, cognitive impairment, cardiovascular morbidity, hospitalizations, and mortality. As the prevalence of end-stage renal disease continues to rise, the management of anemia represents a growing economic burden. Erythropoiesis-stimulating agents (ESA) are the mainstay of anemia management but their use is limited due to the associated cardiovascular adverse events. Prolyl hydroxylase domain enzyme (PHD) inhibitors are a new class of drugs that stabilize the hypoxia-inducible factors and are under clinical investigation for the treatment of renal anemia. The advantages of PHD inhibitors include the oral route of administration, improved iron profile, restoration of diurnal rhythm of erythropoietin secretion, and endogenous erythropoietin production near physiological range. Emerging but limited data indicates a small blood pressure lowering effect of PHD inhibitors. The effect of PHD inhibitors on cardiovascular endpoints and the potential risks of CKD progression and pulmonary hypertension remains to be addressed in the ongoing clinical trials.