-  Home 
        -  About NIDDK 
        -  Research Areas 
        -  Kidney Disease 
        -  Effects of Chronic Kidney Disease in Adults Study: CRIC 

Kidney Disease
-  Chronic Kidney Disease in Children Study: CKiD 
-  Effects of Chronic Kidney Disease in Adults Study: CRIC 

# Effects of Chronic Kidney Disease in Adults Study: CRIC

The Chronic Renal Insufficiency Cohort (CRIC) Study is one of the largest and longest ongoing studies looking at the causes, frequency, and consequences of chronic kidney disease (CKD) in the United States. The NIDDK supports the CRIC Study to better understand
          - what makes CKD worsen and result in complete loss of kidney function or kidney failure
          - the link between CKD and cardiovascular disease (heart and blood vessel disease or CVD) that is commonly seen in people with CKD

The study is also building on more than 17 years of detailed information gathered by looking at what affects CKD and how CKD affects people's health and life.

Approximately 15 percent of Americans have CKD, and more than 726,000 people in the United States depend on kidney replacement therapy (dialysis or transplant) to treat kidney failure. The costs of CKD and kidney failure in the United States billed to Medicare is more than $120 billion per year. Treatment of kidney failure alone costs about $36 billion each year, according to the U.S. Renal Data System. 

Understanding the risk factors that cause CKD to worsen and why patients with CKD frequently have cardiovascular disease will help researchers design clinical trials to test treatments that may reduce the impact of CKD.

## Results

The CRIC Study investigators have made important discoveries.
          - African Americans who have high risk variants of the  APOL1  gene are about one and a half to two times more likely to experience a big loss of kidney function or kidney failure compared to Caucasians. This finding has led to additional research to determine how this gene increases risk of poor outcomes in African Americans with CKD and to look for potential new therapies to improve outcomes in those with high risk variants of the  APOL1  gene.
          - High levels of a hormone called fibroblast growth factor 23 (FGF 23)—which controls the amount of phosphorus, a mineral, in the blood—are linked to a higher risk of kidney failure and death. This finding led to a pilot clinical trial, supported by the NIDDK, to test whether FGF 23 and phosphorus levels can be lowered by medicines. A larger study will be necessary to find out whether lowering FGF 23 and phosphorus levels can slow the worsening of CKD and lower the risk of cardiovascular disease and death.
          - Increased sodium in a person’s urine—a measure of salt intake from the person’s diet—is associated with increased risk of cardiovascular disease. Whether reducing dietary salt intake lowers the chances that a CKD patient will also have cardiovascular disease could be tested in a clinical trial.
          - Certain measurements of inflammation and kidney function were linked to more cardiovascular disease events, including heart attack, stroke, and narrowing of the arteries. These measurements may be used to estimate the risk of cardiovascular disease events or death in people with CKD.
          - In older adults with CKD, lower levels of kidney function were associated with lower levels of cognitive function or the brain’s ability to think, remember, or reason. More research is needed to determine whether certain measurements may be used or treatments may be developed to help cognitive function in older adults with advanced CKD.

## Study Size, Participant Demographics, and Study Design

The CRIC Study has been funded since 2001 and has occurred in four phases.

### Phase 1

Phase 1 took place from 2003 to 2008. Phase 1 enrolled more than 3,900 adults with CKD. Phase 1 also enrolled a second group of 327 adults, called the Hispanic Chronic Renal Insufficiency Cohort (HCRIC), from 2005 to 2008 to increase the number of Hispanic/Latino participants. Participants had the following characteristics.
          - All participants had CKD, but the severity of the disease—how well their kidneys       functioned—varied.
          - Half of the participants also had type 2 diabetes.
          - Participants included approximately equal numbers of men and women.
          - Participants included Caucasians (42 percent), African Americans (42 percent), Hispanics/Latinos (12 percent), and Asian Americans/Pacific Islanders/American Indians       (4 percent).

Participants had their height, weight, blood pressure, and heart rates measured yearly from the beginning of Phase 1. Blood and urine samples were taken at the beginning of Phase 1 and at yearly clinical visits to study the severity of participants’ CKD and cardiovascular disease. A wide range of additional measures were taken throughout the study for cardiovascular health, cognitive and physical health, and quality of life.

Participants continued to receive normal medical care from their own health care providers and did not receive additional medical care as a part of the study.

### Phase 2

Phase 2 took place from 2008 to 2013. Researchers continued to study participants from Phase 1 and began looking at whether they had eye disease due to type 2 diabetes, high blood pressure, and other health problems.

Phase 2 also collected medical histories from participants each year, including the medicines they took, weight, quality of life, diet, and physical activity levels. Some participants had their blood pressure taken more often and received other tests, such as eye scans and measures for cardiovascular health.

### Phase 3

Phase 3 took place from 2013 to 2018. Researchers continued to study participants from Phases 1 and 2, and an additional 1,500 participants were recruited. Phase 3 focused on the effects of CKD and cardiovascular disease in older adults and the risk factors that contribute to the progression of CKD.

### Phase 4

Phase 4 began in August 2018 and will continue to follow participants from Phases 1, 2, and 3 for an additional 5 years. HCRIC recruited an additional 125 Hispanic/Latino participants for Phase 4. Phase 4 uses mobile technologies to collect information about kidney and cardiovascular health in the participants’ home setting.

During this phase, there will also be new recruitment to establish a subgroup of American Indian participants from the Southwest United States.

### Study Sites

The CRIC study's data coordinating center is located at the University of Pennsylvania. The study is currently conducted by researchers at 13 clinical sites in the United States
          - Johns Hopkins University ProHealth, Baltimore, Maryland
          - Kaiser Permanente of Northern California, Oakland, California
          - MetroHealth Medical Center, Cleveland, Ohio
          - St. John Health System, Tulsa, Oklahoma
          - The Cleveland Clinic Foundation, Cleveland, Ohio
          - Tulane Office of Health Research, New Orleans, Louisiana
          - University of California San Francisco, San Francisco, California
          - University Hospitals Case Medical Center, Cleveland, Ohio
          - University of Illinois at Chicago, Chicago, Illinois
          - University of Maryland, Baltimore, Maryland
          - University of Michigan Hospital and Health Systems, Ann Arbor, Michigan
          - University of Pennsylvania – Renal Research, Philadelphia, Pennsylvania
          - Wayne State University School of Medicine, Detroit, Michigan

## Related Health Information

          - Chronic Kidney Disease

## News Releases and Reports

          - Identifying patients with chronic kidney disease who are at increased risk of death
          - NIH: Gene hastens kidney disease progression in African Americans
          - NIH expands study to better understand kidney disease progression
          - Deterioration in heart function associated with progression to kidney failure

## Scientific Publications and Resources

          - CRIC Study Website
          - CRIC Study on ClinicalTrials.gov
          - CRIC Study Documents and Resources on the NIDDK Central Repository
          - CRIC Grant Award Information on dkNET
          - Feldman HI, Appel LJ, Chertow GM, et al.  The Chronic Renal Insufficiency Cohort (CRIC) Study: design and methods .  Journal of the American Society of Nephrology.  2003;14(suppl 2):S148–S153. doi:10.1097/01.asn.0000070149.78399.ce
          - Parsa A, Kao WH, Xie D, et al.  APOL1 risk variants, race, and progression of chronic kidney disease .  New England Journal of Medicine.  2013;369(23): 2183–2196. doi:10.1056/NEJMoa1310345
          - Denker M, Boyle S, Anderson AH, et al.  Chronic Renal Insufficiency Cohort Study (CRIC): overview and summary of selected findings .  Clinical Journal of the American Society of Nephrology.  2015;10(11):2073–2083. doi:10.2215/CJN.04260415
          - Yaffe K, Ackerson L, Kurella Tamura M, et al.  Chronic kidney disease and cognitive function in older adults: findings from the Chronic Renal Insufficiency Cohort Cognitive Study .  Journal of the American Geriatrics Society . 2010;58(2):338–345. doi:10.1111/j.1532-5415.2009.02670.x
          - Amdur RL, Feldman HI, Dominic EA, et al.  Use of measures of inflammation and kidney function for prediction of atherosclerotic vascular disease events and death in patients with CKD: findings from the CRIC Study   (PDF, 585.73 KB)    .  American Journal of Kidney Diseases . 2018;73(3):344–353. doi:10.1053/j.ajkd.2018.09.012
          - Mehta R, Cai X, Lee J, et al.  Association of fibroblast growth factor 23 with atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study .  JAMA Cardiology . 2016;1(5):548–556. doi:10.1001/jamacardio.2016.1445