June 4, 2014
Adopting New Definition of Kidney Disease for Clinical Trials Could Accelerate Development of New Treatments
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health suggests that new therapies for kidney disease could be developed more quickly by revising the definition of kidney disease progression used during clinical trials. If adopted, the new definition could shorten the length of some clinical trials and also potentially encourage more clinical trials in kidney disease. The findings will be published in the June 3, 2014 online edition of the Journal of the American Medical Association.Chronic kidney disease (CKD) is a worldwide public health problem that affects 26 million Americans in the U.S., with 600,000 requiring dialysis or kidney transplantation. Despite its prevalence, there are fewer clinical trials for kidney disease than any other common disease. In December 2012, the National Kidney Foundation (NKF) and the Food and Drug Administration (FDA), challenged the research community to evaluate the current definition of kidney disease progression and examine whether improvements were possible. At that time, NFK and FDA officials viewed favorably emerging evidence that a decline in estimated kidney function was promising as a reliable indicator of kidney disease progression. This research grew directly out of the NFK-FDA challenge.
For the study, a global Chronic Kidney Disease Prognosis Consortium led by Josef Coresh, MD, PhD, MHS, a professor at the Bloomberg School, analyzed data from 1.7 million participants recruited into 35 cohorts in dozens of countries from 1975-2011 and followed for an average of 5 years. The researchers’ points of comparison were the FDA’s current definition of CKD disease onset for clinical trials -- a doubling of serum creatinine, a blood marker that assesses kidney function – and the emerging evidence on a decline in estimated kidney function.
Researchers first analyzed kidney disease progression among all participants during a baseline period of two years. They then examined how this progression predicted subsequent disease progression to the observed 12,344 cases of end-stage renal diseases (ESRD) and 223,944 deaths. The study found that the current serum-creatinine standard used in clinical trials which is associated with a 57% reduction in kidney function carried very high risk – a 32-fold increased risk of ESRD and 3.7-fold increased risk of mortality but only occurred in less than 1% of participants in the two-year baseline period.
In contrast, a 30% decline in kidney function, also measured by serum creatinine levels, occurred in 7% of participants in the two-year baseline period. This was associated with a 5-fold higher risk of end-stage renal disease (ESRD) and 1.8-fold higher risk of mortality. This level of risk is high and yet common and early enough to facilitate testing if new therapies are working.
“Chronic kidney disease is often asymptomatic until it’s too late,” notes Dr. Coresh. “This new definition will help standardize following patients to determine when their disease progresses significantly enough to elevate risk. This will assist in patient care, research studies and development of new therapies”.
The findings were presented by Dr. Coresh at the European Renal Association-European Dialysis and Transplant Association Congress in Amsterdam on Tuesday, June 3, 2014.
“Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality: A consortium meta-analysis” was written by Josef Coresh, MD, PhD, MHS; Tanvir Chowdhury Turin, MD, PhD; Kunihiro Matsushita, MD, PhD; Yingying Sang, MSc, Shoshana H Ballew, PhD; Lawrence J. Appel, MD; Hisatomi Arima, MD; Steven J. Chadban, PhD; Massimo Cirillo, MD; Ognjenka Djurdjev, MSc; Jamie A Green, MD; Gunnar H Heine, MD; Lesley A Inker, MD; Fujiko Irie, MD, PhD; Areef Ishani, MD, MS; Joachim H. Ix, MD, MAS; Csaba P. Kovesdy, MD; Angharad Marks, MBBCh; Takayoshi Ohkubo, MD, PhD; Varda Shalev, MD; Anoop Shankar, MD; Chi Pang Wen, MD, DrPH; Paul E. de Jong, MD, PhD; Kunitoshi Iseki, MD, PhD; Benedicte Stengel, MD, PhD; and Ron T. Gansevoort, MD, PhD; and Andrew S Levey, MD for the CKD Prognosis Consortium.
The Chronic Kidney Disease Prognosis Consortium data coordinating center is funded in part by a program grant from the U.S. National Kidney Foundation (funding sources include AbbVie and Amgen) and the National Institute of Diabetes and Digestive and Kidney Diseases. Other funding sources include government agencies such as institutes of health and medical research councils as well as foundations and industry sponsors listed in eAppendix 3 in the supplement of the JAMA article.