PHILADELPHIA — A $17.5 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will propel Penn Medicine research efforts to prevent Chronic Kidney Disease (CKD). Harold I. Feldman, MD, MSCE, chair of Biostatistics, Epidemiology and Informatics and director of the Center for Clinical Epidemiology and Biostatistics, and J. Richard Landis, PhD, a professor of Biostatistics, Epidemiology and Informatics, will lead the work.
Approximately 15 percent of the U.S. population – more than one in seven people – lives with CKD, according to the Centers for Disease Control. These individuals are far more at risk for heart disease and stroke. Startlingly, more than 90 percent of people with CKD are not aware of their impaired kidney function, which can progress into kidney failure, often resulting in the need for dialysis or even a kidney transplant. The grant will allow the team to gather and study data from home and community settings of more than 3,000 adults who have CKD. These participants are part of the Chronic Renal Insufficiency Cohort (CRIC) Study, the nation’s largest clinical CKD laboratory. Since 2001, the CRIC study, for which Feldman and Landis lead the Scientific and Data Coordinating Center, has enrolled and followed more than 5,500 people. This latest phase of the study will be conducted between 2018 and 2023.
“By bringing together biostatisticians, epidemiologists and informaticians, we are delving deeper into this public health threat in an effort to identify potential interventions that can be tailored to the individual needs of patients suffering with CKD,” said Feldman, who also serves as national study chair of the nationwide CRIC study.
The current round of funding focuses on two paths of research.
Knowing that those with CKD have a significantly higher risk of cardiovascular illness, investigators will use mobile health trackers to measure physical activity, physiology, and heartbeat data in participants living their everyday lives. The goal is to identify patients at highest risk of cardiovascular complications who may be able to receive effective preventative treatments.
The second project will focus on the path of declining kidney function, detecting periods of transient reductions in function that are thought to be an important cause of kidney disease progression over time. These reductions in kidney function will be detected by having participants, in their homes, regularly use finger-stick blood samples to measure creatinine, a primary measure of kidney function and the organs’ ability to filter toxins from the blood. Participants will also give urine samples in which protein levels, another indication of kidney function, will be repeatedly measured. The team will look at both in conjunction with behaviors and exposures that may account for changes in kidney function. For example, did kidney function drop after a person ran a race or changed medications? The hope is that this component of the CRIC Study will shed light on the causes of transient kidney dysfunction, identify its role in progressive kidney disease, and offer insights into effective preventive strategies.
The $17.5 million grant is part of a $40 million National Institutes of Health-funded program also supporting the 11 sites nationwide where CRIC Study participants are enrolled and closely monitored. One of these sites is also at Penn, led by Ray Townsend, MD, a professor of Medicine, who follows more than 500 CRIC Study participants.
The CRIC Study aims to build on earlier achievements in the understanding of the development and management of CKD. These include, more recently, the finding that African Americans with the APOL1 gene variant experience faster progression of CKD and have a significantly increased risk of kidney failure, reported in the New England Journal of Medicine, as well as the CRIC Study reported in the Annals of Internal Medicine, which showed that earlier studies under-reported the relationship between high blood pressure and CKD progression. This study highlighted that blood pressures above 130/80—the threshold in the new American Heart Association guidelines—were associated with progression of the disease.
Feldman and Landis are co-principal investigators on the NIH grant, 2U24DK060990-18. Additional Penn collaborators include Laura Dember, Jordana Cohen, John Holmes, Scott Kasner, Steve Messe, Rajat Deo, Jesse Yenchih Hsu, Dawei Xie, and Wei (Peter) Yang. Townsend’s grant, 2U01DK060984-18 also includes, as collaborator, Debbie Cohen.
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