Abstract
Background and objectives Patients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2–4. Design, setting, participants, & measurements Among 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T50 ) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality. Results The mean T50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T50, 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T50, 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T50, 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T50, 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality. Conclusions Among patients with CKD stages 2–4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1562-1571 |
| Number of pages | 10 |
| Journal | Clinical Journal of the American Society of Nephrology |
| Volume | 14 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 7 2019 |
Funding
Dr.Blockreportsreceiving agrant,researchsupport, andpersonal fees as an advisor and consultant and for travel from Keryx/Akebia; honoraria and personal fees as a Director and consultant and for travel from Ardylex, and nonfinancial support and personal fees as a consultant and for travel from Amgen, AstraZeneca, Kirin, and OPKO, outside of the submitted work. Dr. Block is also an employee of Reata Pharmaceuticals. Dr. de Boer reports receiving consultant fees, honoraria, or nonfinancial research support, including consulting fees from Boehringer Ingelheim and Ironwood and equipment and supplies for research from Abbott Laboratories and Medtronic, outside the submitted work. Dr. Dobre reports an R01 grant (SPRINT-Myocardial Fibrosis) from the National Heart, Lung, and Blood Institute (NHLBI); personal fees from Relypsa for the Resistant Hypertension Working Group; and personal fees from Tricida for the Metabolic Acidosis Working Group, outside the submitted work. Dr. Feldman reports consulting fees from Kyowa Hakko Kirin Co., Ltd and an Editor-in-Chief position with the American Journal of Kidney Diseases. Dr. Isakova reports receiving consulting fees from Bayer and Eli Lilly and other support from Shire. Dr. Mehta reports owning stock in Abbott Laboratories, AbbVie Inc., and Teva Pharmaceutical Industries. Dr. Pasch is an inventor of the T50 test and a stockholder of Calciscon AG (Nidau, Switzerland), which commercializes the test used in this study. Dr. Scialla reports receiving fees from Eli Lilly, GlaxoSmithKline, and Sanofi for the support of Clinical Event Committee activities outside of the submitted work. Dr. Smith reports receiving investigator-initiated research study grant funding from Amgen, Baxter, and Sanofi outside of the submitted work and that he is a stockholder of Calciscon AG. Dr. Bundy, Dr. Cai, Dr. Chen, Dr. Go, Dr. Hsu, Dr. Lash, Dr. Leonard, Dr. Rao, and Dr. Townsend have nothing to disclose. This work was supported by the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK; grant P30DK114857). Dr. Bundy is supported by the NHLBI Cardiovascular Epidemiology training grant T32HL069771. Dr. de Boer is supported by a grant from NIDDK (R01DK099199). Dr. Dobre is supported by a grant from NHLBI (R01HL141846). Dr. Isakova is supported by grants from NIDDK (R01DK102438, R01DK110087, and U01DK099930). Dr. Scialla is supported by a grant from NIDDK (R01DK111952). Fundingfor the Chronic Renal Insufficiency Cohort study was obtained under a cooperative agreement from NIDDK (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 National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR000003), the Johns Hopkins Institute for Clinical and Translational Research (UL1TR000424), University of Maryland General Clinical Research Center (M01RR-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 Center of Biomedical Research Excellence for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036), and Kaiser Permanente National Institutes of Health/National Center for Research Resources University of California San Francisco Clinical and Translational Science Institute (UL1RR024131). This work was supported by the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK; grant P30DK114857). Dr. Bundy is supported by the NHLBI Cardiovascular Epidemiology training grant T32HL069771. Dr. de Boer is supported by a grant from NIDDK (R01DK099199). Dr. Dobre is supported by a grant from NHLBI (R01HL141846). Dr. Isakova is supported by grants from NIDDK (R01DK102438, R01DK110087, and U01DK099930). Dr. Scialla is supported by a grant from NIDDK(R01DK111952).FundingfortheChronicRenalInsufficiency Cohort study was obtained under a cooperative agreement from NIDDK (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 National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR000003), the Johns Hopkins Institute for Clinical and Translational Research (UL1TR000424), University of Maryland General Clinical Research Center (M01RR-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 Center of Biomedical Research Excellence for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036), and Kaiser Permanente National Institutes of Health/National Center for Research Resources University of California San Francisco Clinical and Translational Science Institute (UL1RR024131).
ASJC Scopus subject areas
- Epidemiology
- Critical Care and Intensive Care Medicine
- Nephrology
- Transplantation
