Bringing a 2020 Focus to Clinical Trials in Kidney Health and Disease: A Call for Action

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.

Reasons for optimism

Still, there are great reasons for optimism. A rudimentary evaluation of (5) today suggests 6380 trials in kidney disease. This suggests an uptick in activity as compared with just several years back (1). As opposed to decades ago, when late-breaking clinical trials were largely yielding negative results, recent years have brought some apparent successes in intervention (such as rituximab in membranous nephropathy, sodium-glucose co-transporter protein 2 inhibition and perhaps endothelin blockade in diabetes, tolvaptan in polycystic kidney disease, and novel anemia therapies proving effective).

The US Food and Drug Administration has been active in evaluating and occasionally approving new endpoints for clinical trials, which is one suggestion that the efforts of the Kidney Health Initiative may be paying large dividends. Several examples suggest that nephrologists are indeed working together in broader collaborations to bring about meaningful guidelines and to spur interest in clinical trials. Patient advocacy groups have been successful in extolling the virtues and central importance of patient-reported outcomes as part of research studies, allowing for greater interest and participation of patients in ongoing and upcoming trials. Journals, guideline organizations, and regulatory bodies seem increasingly interested in using the results of innovative study designs to inform or determine clinical decision-making.

More effective and value-based care is an absolute necessity for maintaining kidney health and for treating patients with kidney disease. Not only is kidney disease a common issue affecting many millions of people, but also it is one that imposes tremendous suffering and a huge cost, both nationally and internationally. Advancements in care depend on the development of sound interventions for properly targeted populations that are each subjected to appropriate and well-designed clinical trials to allow the determination of their safety, efficacy, and impact on patients’ well-being. Progress is being made. Still, further efforts to increase clinical trials are desperately needed. We must build on caregiver interest, patient participation, stakeholders’ involvement, and funding, and we must develop increasing expertise in the design and execution of optimal clinical trials for our well-deserving population.

February 2020 (Vol. 12, Number 2)


1. Inrig JK, et al The landscape of clinical trials in nephrology: A systemic review of Am J Kidney Dis 2014; 63:771–780.

3. 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.

4. 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.

5. Perkovic V, et al Action plan for optimizing the design of clinical trials in chronic kidney disease. Kidney Int Suppl 2017; 7:138–144.