Momentum toward patient outcome trials in chronic kidney disease-mineral bone disorder

The purpose of this review is to: evaluate the clinical trial evidence base for the treatment of chronic kidney disease mineral and bone disorder (CKD-MBD) in patients with kidney failure as it relates to highly prioritized clinical outcomes; and discuss approaches and principles to develop needed trials in CKD-MBD.

Most clinical trials in CKD-MBD focus on biochemical outcomes, with few trials of surrogate outcomes (e.g., vascular calcification, left ventricular hypertrophy, bone mineral density), and even fewer of highly prioritized clinically important outcomes, such as mortality, cardiovascular disease events, or hospitalization. Within phosphate management, the recent LANDMARK trial did not detect a difference in a cardiovascular composite outcome between patients randomized to lanthanum carbonate vs. a calcium-based phosphate binder strategy over 3 years. The ongoing PHOSPHATE trial will provide needed evidence on phosphate treatment targets. There are no comparable, large trials of parathyroid hormone (PTH) targets. Observational approaches using clinical trial emulation suggest the potential for reduced cardiovascular disease and mortality with an 'emulated' low PTH target, but trials must be designed to confirm this. To ensure success, these trials must focus on practical treatment approaches, leveraging areas of practice variation and recognizing the dynamic nature of longitudinal CKD-MBD care.

More intensive treatment of CKD-MBD remains a promising approach to improve clinical outcomes in patients with kidney failure and should prompt ongoing efforts to obtain needed trials.