Despite the high prevalence of kidney disease in the U.S. there are few treatments available to directly treat it. The underlying causes of kidney disease are diverse and the progression of kidney dysfunction is slow and often without symptoms. How do scientists efficiently test drugs to slow progression of kidney disease when benefits to patients are not evident for many years?
In patients who have already progressed to end stage renal disease (ESRD), how do scientists determine when a drug used to treat a symptom or co-morbidity, such as anemia or high phosphorus, is of significant value in improving the health and well-being of the patient? How is it decided if the benefits of the therapy outweigh the potential adverse side effects or warrant the additional costs?
These questions provide significant challenges in developing clinical trials to test the efficacy of new medications to treat patients with kidney disease and limit the availability of effective treatments. In an effort to address these issues the National Kidney Foundation (NKF) has collaborated with the U.S. Food and Drug Administration (FDA) to facilitate a series of scientific workshops. These meetings bring together experts in clinical trial design and epidemiology (the scientific study of disease patterns, causes and effects), representatives from the FDA, other government agencies and health organizations, such as the National Institutes of Health, the Critical Path Institute, and the European Medicines Agency, as well as dialysis and pharmaceutical industry representatives; and other kidney related patient and professional organizations, including the American Diabetes Association, American Society of Nephrology, and the Polycystic Kidney Disease Foundation. The objectives of these meetings are to present and discuss the state-of-the-art research findings and make recommendations on how to interpret and use the information to advance the clinical development of effective treatments in kidney disease.
The most recent NKF/FDA Scientific Workshop evaluated how declines in estimated glomerular filtration rate (eGFR) could be used to determine the efficacy of a drug. The FDA currently uses doubling of serum creatinine level, which equates to a 57% reduction in eGFR, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression because it represents a marked loss of kidney function and because it is expected to be highly predictive of the development of kidney failure. However, a doubling of serum creatinine is generally a late event in CKD and takes a long time to develop. In preparation for this workshop analytic teams at Tufts and John Hopkins University analyzed data from dozens of studies and presented the results during the workshop. Based on these extensive analyses the workshop planning committee and attendees recommended a 30 or 40% decline in GFR as new surrogate endpoints for some clinical trials in CKD used for regulatory approval. Based on these findings the FDA is now considering these lessor declines in eGFR as adequate indicators of drug effectiveness in some clinical trials used to get approval for new drugs to treat CKD.
The National Kidney Foundation values the relationship and will continue to collaborate with the FDA to promote development of therapies that can improve outcomes for people with CKD.