The National Kidney Foundation’s Role in Advancing Clinical Trials in Nephrology

Advancing Clinical Trials in Kidney Disease

Historically, kidney disease treatments were limited, with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) being the primary options. However, recent developments have introduced specific treatments like sodium-glucose cotransporter-2 (SGLT2) inhibitors and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) that delay disease progression.

Dr. Willis highlights the NKF’s decade-long effort to establish surrogate endpoints for clinical trials, such as changes in glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). These efforts, in collaboration with regulatory bodies like the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have revolutionized clinical trial methodologies, enabling shorter, more feasible studies.

Dr. Willis explains, “We’ve been working for about ten years to validate surrogate endpoints for use in clinical trials. We work closely with the cardiorenal division of the FDA and have been able to get a 30 percent or a 40 percent decline in GFR or also a change in the slope of decline to be validated endpoints and also specific reductions in the urine ACR.”

The NKF also plays a crucial role in patient advocacy, maintaining a comprehensive Kidney Diseases Clinical Trial Directory to inform patients about ongoing clinical trials, ensuring wider participation, and enhancing the diversity of treatment options available.

The NKF is also conducting the KidneyCARE Study, where patients can contribute to research by sharing their personal experiences with kidney disease through survey responses. This includes a comprehensive registry of individuals at every stage and with all forms of kidney disease.

Addressing Enrollment Challenges

In addressing the substantial challenges of patient enrollment in clinical trials for kidney disease, Dr. Willis lists some barriers that prevent broader participation. She highlights a stark reality: Only a fraction of those affected by kidney disease in the US are aware they have it — about ten percent. This low diagnosis rate severely limits the pool of potential participants for clinical studies.

Dr. Willis emphasizes, “There are about 37 million people who have kidney disease in the US. And there are a lot of barriers to clinical trial participation including that people with kidney disease tend to be disproportionately affected by social determinants of health.”

Socioeconomic factors play a substantial role in limiting trial participation. Many patients with kidney disease have lower socioeconomic status, which can restrict their ability to travel to trial sites, often located in major academic medical centers. The need for regular travel, taking time off work and the overall logistics of participating can be daunting for many.

“We’ve been very active in collecting data, performing meta-analyses and working with the FDA and EMA.

We’re a patient advocacy organization but we’re also an innovator in the kidney disease space. We have a very large database of patients at all stages of kidney disease and we assist with letting people know about clinical trials that they might be eligible for.”

 

— Dr. Kerry Willis

To mitigate these challenges, Dr. Willis thinks decentralized clinical trials can substantially reduce the need for physical travel by allowing data collection and monitoring to happen remotely. She is optimistic about this approach, stating, “If you’re in a partially or fully decentralized trial, then having to take time off work and other burdens are less of a barrier.”

Dr. Willis also discusses the mistrust in the healthcare system, particularly among communities disproportionately affected by kidney disease, such as African Americans and Hispanics.

She notes, “Building trust is essential, and it’s one of the hardest barriers we face. Historical inequities in healthcare contribute to this distrust, and we need to address these directly.”

Furthermore, initiatives like Kidney Research Connect aim to bridge the gap between patients and researchers, fostering a more patient-centered approach in trial design and execution. Kidney Research Connect is an online platform that connects patients and caregivers with researchers focused on patient-centered outcomes research (PCOR).