This is a highly exciting year for nephrology. We will all need not only to watch but to participate in bringing about positive changes in healthcare for preventing and treating kidney diseases, hoping for strong support from the Advancing American Kidney Health initiative. One of the strongest reasons for enthusiasm, and one of the most important aspects, will be advancing clinical trials in nephrology.
Clinical trials are the lifeblood of advancing medicine. To truly improve kidney care, we must be able to subject our treatments to rigorous high-quality trials in the appropriate patients and to evaluate them for the appropriate endpoints.
Only a few years ago, the status of clinical trials in kidney health and disease was quite disappointing (1). There was a long repeated history of multiple good ideas going by the wayside with unanticipated negative results (which is why trials are done) or underpowered incomplete trials. There are multitudes of examples. Hopes that fully corrective anemia therapy was safe and beneficial for our patients with advanced chronic kidney disease went unrealized; studies actually suggested harm. Preliminary data suggesting that more intensive dialysis would extend lives was similarly unsupported by clinical trials. Multiple studies failed to verify that seemingly promising interventions for acute kidney injury were indeed useful.
Beyond this, analyses suggested that despite the great need for validating and improving the care of patients with kidney disease—a very large, often ill, and cost-intensive population—there was relatively little in the way of documented clinical trial activity. Furthermore, the ongoing trials seemed to be relatively lacking in quality or potential impact. This was distinct from what was seen in other well-funded, high-visibility fields such as cardiology, oncology, and AIDS research. Limitations suggested to explain this scarcity included lack of federal funding for kidney disease, limited excitement by industry (fueled in part by frustration in the field from negative studies such as those above), and a limited infrastructure to carry out studies in an efficient and effective manner. These and other serious challenges were cited in a Kidney Disease—Improving Global Outcomes controversies conference (2) calling for desperate action to improve clinical trials in kidney disease.
These issues were further explored during a Global Kidney Health Summit in 2017 (3, 4). The participants reviewed and reported numerous factors responsible for the limited number and impact of clinical trials in kidney disease. These factors included limited knowledge of biologic targets, unclear relevant endpoints, lack of innovative trial designs, inadequate capacity to perform trials, uncertainty of what stage disease(s) to target, duplicative study designs, and a perception that trials are too expensive and high risk among kidney disease populations.
The participants expressed the aim of overcoming these limitations with a push toward funding more basic research, working on understanding and validating effective biomarkers as endpoints, engaging patients to be recruited for and participate in studies, including more kidney disease patients in active studies of general health trials (e.g., cardiology, oncology, diabetes), and engaging industry, advocacy groups, and physicians to substantially increase the number and size of clinical trials.
As an example of solutions, they advocated for innovative study design, moving somewhat from slow-moving, hard-to-recruit, and expensive prospective double-blind randomized control trials to more novel approaches such as randomized registry trials, cluster randomized trials, and adaptive trial designs. Most important, they endorsed the effort to increase the capacity for conducting clinical trials by developing networks nationally and internationally, cataloging sites whose personnel have the skill set to participate and to develop and provide more professional training in trial design and conduct. They targeted achieving the participation of 30% of patients with chronic kidney disease in trials by 2030. This action plan has great aspirations and merit, but it still requires huge coordination and funding to pull it off.
Inrig JK, et al. The landscape of clinical trials in nephrology: A systemic review of clinicaltrials.gov. Am J Kidney Dis 2014; 63:771–780.
Baigent C, et al. Challenges in conducting clinical trials in nephrology: Conclusions from a Kidney Disease—Improving Global Outcomes Controversies Conference. Kidney Int 2017; 92:297–305.
Levin A, et al. Global kidney health 2017 and beyond: A roadmap for closing gaps in care, research, and policy. Lancet 2017; 390:1888–1917.
Perkovic V, et al. Action plan for optimizing the design of clinical trials in chronic kidney disease. Kidney Int Suppl 2017; 7:138–144.