Throughout the world, kidney disease is far more common than most people realize. It’s not a stretch to call it a “hidden epidemic,” as the number of people living with kidney disease (850 million) is roughly twice that of those living with diabetes.(1)
The health issue presented by chronic kidney disease (CKD) is magnified by the high prevalence of associated cardiovascular (CV) disease in these patients. Patients with CKD most commonly die from CV events.(2) Also, among patients with CV disease, 30 to 60 percent have kidney disease.(3)
Despite this tight relationship between kidney and CV disease, patients with CKD are frequently excluded from cardiovascular (CV) clinical trials. The latest systemic review of CV trials published between 2006 and 2013 found that more than half (57 percent) excluded patients with kidney disease.(4) Failure to include CKD patients in CV trials leads to gaps in the data we have about the efficacy and safety of common drugs in our CKD patients and the value of new breakthrough therapies in treating their CV disease.
The lack of available evidence on safety and efficacy of CV interventions in CKD patients makes it challenging to manage CV disease in CKD patients. We have not investigated CKD patients with CV disease as frequently as we should, so relevant data is not as robust as it would be if they had been studied directly in trials.
The Little-Known Facts about CKD
Chronic kidney disease (CKD) is defined as any abnormality in the structure or function of kidneys that persists more than three months. Did you know:
- The prevalence of CKD is roughly double the number of people who live with diabetes(6) and 20 times more than the prevalence of cancer (42 million) (7)
- The annual cost per patient for hemodialysis in the US is $88,195 (8)
- Each year, Medicare spends $99 billion (6% of its budget!) on CKD patients
- Declining kidney function is associated with worse outcomes (9):
- Increasing CV event rates of 22 and 36 (per 100 person years) respectively for Stage 4 CKD (eGFR of 15-29 ml/mim/m2) and Stage 5 (eGFR <15 ml/mim/ m2)
- Strikingly high death rates of 11 and 14 (per 100 person years), respectively for Stage 4 and 5 CKD
One group who assesses such gaps in renal drug and device development is the Kidney Health Initiative (KHI), which is a novel public-private partnership between the American Society of Nephrology (ASN) and the U.S. Food & Drug Administration (FDA). I serve on the Board of Directors, and with our 90+ stakeholder members, we’d like to see more drugs and medical devices approved for use in patients with kidney disease. One particular workgroup, chaired by cardiologist Dr. Charles Herzog and nephrologist Dr. Julie Ishida, seeks to identify barriers and solutions for including CKD patients with stage 4 CKD (eGFR(5) of 15-29 ml/mim/m2) and those with Stage 5 and on dialysis, in more CV clinical trials.
Making Progress: The Recent KHI Workshop
In the December 2017 Cardiovascular Clinical Trialists Forum (CVCT), our KHI Workgroup participated in a panel dedicated to CKD and launched a survey for both patients and industry stakeholders (including sponsor companies) to explore the reasons that CKD patients are so often excluded from clinical trials. The results of the survey were presented in a workshop held in early September 2018 and attended by participants from the U.S. FDA, Health Canada, nephrologists, cardiologists, patients and drug & device sponsors. I co-moderated one of the four breakout sessions, and my Covance cardiology colleague, Dr. Jonathan Plehn, also represented Covance in a group focusing on trial design. He noted, “Going into this meeting I was unaware of the degree to which CKD patients have been excluded from our CV trials. The reasons for this are often not well considered. Thus, the KHI meeting was a unique opportunity to directly exchange insights between the two specialties and with regulators and patients…a great collaborative meeting.”
The discussion groups were tasked with identifying the challenges of, and solutions to, four aspects of the issue: study design, feasibility/finances and patient engagement. On the basis of the stakeholder perceptions gathered in the survey, each group offered practical recommendations. The outcome of the meeting will be shared in a paper that I am co-authoring for submission to a peer-reviewed journal…Watch for more details.
Dr. Gillespie, a board certified nephrologist, is vice president and therapeutic head of Nephrology at Covance. Additionally, she cares for CKD patients as an adjunct professor at the University of North Carolina, Division of Nephrology. Dr. Plehn is vice president of Cardiovascular Medicine at Covance and a clinical professor of Medicine at Drexel University School of Medicine.
2 Go, A.S., et al., Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. New England Journal of Medicine, 2004;35(13):1296-1305.
3 Kidney Health Initiative, “Kidney Health Initiative Workshop on Understanding and Overcoming the Challenges to Involving Patients with Kidney Disease in Cardiovascular Trials”
4 Konstantinidis, JAMA IM 2016
5 eGFR is the estimated glomerular filtration rate
8 United States Renal Data System. 2017 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2017
9 Go, A.S., et al., Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. New England Journal of Medicine, 2004;35(13):1296-1305