VO 2 Peak: The Emerging End Point For Cardiovascular Outcome Trials in Nephrology.

Cardiovascular outcome trials are challenging to conduct in patients with CKD. Despite this, well-designed randomized controlled trials are critical to inform optimal management strategies and improve clinical care. Unfortunately, many cardiovascular outcome trials in nephrology have not demonstrated a treatment benefit. Contributing to this are the difficulties associated with end point selection and the limitations of many traditional end points such as resting left ventricular geometric measures and circulating biomarkers in patients with CKD, which are well known to be a major impediment to the conduct of cardiovascular trials in this population. The emergence of state-of-the-art cardiopulmonary exercise testing (CPET) technology in nephrology has taken center stage in this field due to the possibilities and solutions afforded by CPET-derived functional end points. CPET is a powerful tool that incorporates ventilatory gas exchange measurements during graded exercise and robustly quantifies VO 2 Peak, the gold standard index for cardiovascular functional capacity. The use of functional end points such as VO 2 Peak is a critical mechanism to promote patient-centered clinical trials in patients with CKD. Furthermore, the US Food and Drug Administration has now approved both drugs and devices that have used VO 2 Peak as an end point outside of nephrology. With accumulating scientific evidence base supporting the rationale for CPET-derived end points in patients with CKD, the potential use of VO 2 Peak in clinical trials as a basis for regulatory approval creates an exciting opportunity in nephrology.