Abstract
Rationale & Objective: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4. Study Design: Prospective cohort study. Setting & Participants: Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n = 1,274) and follow-up (n = 780) CAC measurements. Predictors: Calcification propensity, quantified as transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications. Outcomes: CAC prevalence, severity, incidence, and progression. Analytical Approach: Multivariable-adjusted generalized linear models. Results: At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T50 was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T50 was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase ≥ 100 Agatston units. After multivariable adjustment, T50 was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T50 was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression. Limitations: Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification. Conclusions: Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 806-814 |
| Number of pages | 9 |
| Journal | American Journal of Kidney Diseases |
| Volume | 73 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2019 |
Funding
Lawrence J. Appel, MD, MPH, Harold I. Feldman, MD, MSCE, Alan S. Go, MD, Jiang He, MD, PhD, James P. Lash, MD, Panduranga S. Rao, MD, Mahboob Rahman, MD, and Raymond R. Townsend, MD. Joshua D. Bundy, PhD, MPH, Xuan Cai, MS, Julia J. Scialla, MD, MHS, Mirela A. Dobre, MD, MPH, Jing Chen, MD, Chi-yuan Hsu, MD, MS, Mary B. Leonard, MD, MSCE, Alan S. Go, MD, Panduranga S. Rao, MD, MS, James P. Lash, MD, Raymond R. Townsend, MD, Harold I. Feldman, MD, MSCE, Ian H. de Boer, MD, MS, Geoffrey A. Block, MD, Myles Wolf, MD, MMSc, Edward R. Smith, BSc, MSc, PhD, Andreas Pasch, MD, and Tamara Isakova, MD, MMSc. Designed the study: JDB, TI; collected the data: ASG, PSR, JPL, RRT, HIF, AP, TI; conducted the statistical analyses: JDB, XC; analyzed and interpreted the data: JDB, XC, JJS, MAD, JC, C-yH, MBL, ASG, PSR, JPL, RRT, HIF, IHdB, GAB, MW, ERS, AP, TI. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This work was supported by grants P30DK114857, R01DK102438 (Dr Isakova), R01DK110087 (Dr Isakova), R01DK099199 (Dr de Boer), R01DK081374 (Dr Wolf), R01DK076116 (Dr Wolf), R01DK094796 (Dr Wolf), U01DK099930 (Drs Isakova and Wolf), R01DK111952 (Dr Scialla), and R01HL141846 (Dr Dobre) from the National Institutes of Health (NIH), and a Strategically Focused Research Network Center Grant on Health Disparities from the American Heart Association (Dr Wolf). Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this study was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences UL1TR000003, the Johns Hopkins Infstitute for Clinical and Translational Research UL1 TR-000424, University of Maryland General Clinical Research Center M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Awards UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131. Dr Bundy is supported by the National Heart, Lung, and Blood Institute Cardiovascular Epidemiology training grant T32HL069771. None of the funders of this study had any role in the current study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. Dr de Boer has received research support, honoraria or consultant fees from Abbott, Boehringer Ingelheim, Ironwood, and Medtronic. Dr Block has received research support, honoraria, or consultant fees from Akebia, Amgen, CARA, Davita, Keryx, and Reata. Dr Wolf has received research support, honoraria, or consultant fees from Akebia, Amag, Amgen, Ardelyx, DiaSorin, Keryx, and Shire. Dr Smith has received research support from Amgen and Sanofi and is a stockholder of Calciscon AG (Nidau, Switzerland), which commercializes the test. Dr Pasch is an inventor of the T50 test and a stockholder of Calciscon AG. Dr Isakova has received research support or consultant fees from Bayer, Eli Lilly, and Shire. The authors thank the participants, investigators, and staff of the CRIC Study for their time and commitment. Parts of this manuscript were presented in abstract form at ASN Kidney Week, San Diego, CA, October 23-29, 2018. Received October 14, 2018. Evaluated by 3 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Masafumi Fukagawa, MD, PhD). Accepted in revised form January 25, 2019. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies. Lawrence J. Appel, MD, MPH, Harold I. Feldman, MD, MSCE, Alan S. Go, MD, Jiang He, MD, PhD, James P. Lash, MD, Panduranga S. Rao, MD, Mahboob Rahman, MD, and Raymond R. Townsend, MD. Joshua D. Bundy, PhD, MPH, Xuan Cai, MS, Julia J. Scialla, MD, MHS, Mirela A. Dobre, MD, MPH, Jing Chen, MD, Chi-yuan Hsu, MD, MS, Mary B. Leonard, MD, MSCE, Alan S. Go, MD, Panduranga S. Rao, MD, MS, James P. Lash, MD, Raymond R. Townsend, MD, Harold I. Feldman, MD, MSCE, Ian H. de Boer, MD, MS, Geoffrey A. Block, MD, Myles Wolf, MD, MMSc, Edward R. Smith, BSc, MSc, PhD, Andreas Pasch, MD, and Tamara Isakova, MD, MMSc. Designed the study: JDB, TI; collected the data: ASG, PSR, JPL, RRT, HIF, AP, TI; conducted the statistical analyses: JDB, XC; analyzed and interpreted the data: JDB, XC, JJS, MAD, JC, C-yH, MBL, ASG, PSR, JPL, RRT, HIF, IHdB, GAB, MW, ERS, AP, TI. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This work was supported by grants P30DK114857, R01DK102438 (Dr Isakova), R01DK110087 (Dr Isakova), R01DK099199 (Dr de Boer), R01DK081374 (Dr Wolf), R01DK076116 (Dr Wolf), R01DK094796 (Dr Wolf), U01DK099930 (Drs Isakova and Wolf), R01DK111952 (Dr Scialla), and R01HL141846 (Dr Dobre) from the National Institutes of Health (NIH), and a Strategically Focused Research Network Center Grant on Health Disparities from the American Heart Association (Dr Wolf). Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this study was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences UL1TR000003, the Johns Hopkins Infstitute for Clinical and Translational Research UL1 TR-000424, University of Maryland General Clinical Research Center M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Awards UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131. Dr Bundy is supported by the National Heart, Lung, and Blood Institute Cardiovascular Epidemiology training grant T32HL069771. None of the funders of this study had any role in the current study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. Dr de Boer has received research support, honoraria or consultant fees from Abbott, Boehringer Ingelheim, Ironwood, and Medtronic. Dr Block has received research support, honoraria, or consultant fees from Akebia, Amgen, CARA, Davita, Keryx, and Reata. Dr Wolf has received research support, honoraria, or consultant fees from Akebia, Amag, Amgen, Ardelyx, DiaSorin, Keryx, and Shire. Dr Smith has received research support from Amgen and Sanofi and is a stockholder of Calciscon AG (Nidau, Switzerland), which commercializes the test. Dr Pasch is an inventor of the T This work was supported by grants P30DK114857, R01DK102438 (Dr Isakova), R01DK110087 (Dr Isakova), R01DK099199 (Dr de Boer), R01DK081374 (Dr Wolf), R01DK076116 (Dr Wolf), R01DK094796 (Dr Wolf), U01DK099930 (Drs Isakova and Wolf), R01DK111952 (Dr Scialla), and R01HL141846 (Dr Dobre) from the National Institutes of Health (NIH), and a Strategically Focused Research Network Center Grant on Health Disparities from the American Heart Association (Dr Wolf). Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , and U01DK060902 ). In addition, this study was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/ National Center for Advancing Translational Sciences UL1TR000003 , the Johns Hopkins Infstitute for Clinical and Translational Research UL1 TR-000424 , University of Maryland General Clinical Research Center M01 RR-16500 , Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 , Michigan Institute for Clinical and Health Research UL1TR000433 , University of Illinois at Chicago Clinical and Translational Science Awards UL1RR029879 , Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, and Kaiser Permanente NIH/ National Center for Research Resources UCSF-CTSI UL1 RR-024131. Dr Bundy is supported by the National Heart, Lung, and Blood Institute Cardiovascular Epidemiology training grant T32HL069771. None of the funders of this study had any role in the current study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.
Keywords
- Coronary artery disease
- calcification propensity
- calciprotein particles
- cardiovascular disease (CVD)
- chronic kidney disease (CKD)
- coronary artery calcium (CAC)
- epidemiology
- risk factors
- transformation time (T)
ASJC Scopus subject areas
- Nephrology
