TY - JOUR
T1 - Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD
T2 - The Chronic Renal Insufficiency Cohort (CRIC) Study
AU - CRIC Study Investigators
AU - Isakova, Tamara
AU - Cai, Xuan
AU - Lee, Jungwha
AU - Mehta, Rupal
AU - Zhang, Xiaoming
AU - Yang, Wei
AU - Nessel, Lisa
AU - Anderson, Amanda Hyre
AU - Lo, Joan
AU - Porter, Anna
AU - Nunes, Julie Wright
AU - Negrea, Lavinia
AU - Hamm, Lee
AU - Horwitz, Edward
AU - Chen, Jing
AU - Scialla, Julia J.
AU - de Boer, Ian H.
AU - Leonard, Mary B.
AU - Feldman, Harold I.
AU - Wolf, Myles
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - He, Jiang
AU - Lash, James P.
AU - Ojo, Akinlolu
AU - Rahman, Mahboob
AU - Townsend, Raymond R.
N1 - Funding Information:
This work was supported by grants R01DK102438 (Dr Isakova), R01DK110087 (Dr Isakova), R01DK099199 (Dr de Boer), R01DK111952 (Dr Scialla), R01DK081374 (Dr Wolf), R01DK076116 (Dr Wolf), R01DK094796 (Dr Wolf), K24DK093723 (Dr Wolf), U01DK099930 (Drs Wolf and Isakova), and P30DK114857 from the National Institutes of Health (NIH), and a Strategically Focused Research Network Center Grant on Health Disparities from the American Heart Association (Drs Wolf and Isakova). Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , and U01DK060902 ). In addition, this work 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 ; Johns Hopkins University UL1 TR-000424 ; University of Maryland General Clinical Research Center M01 RR-16500 ; Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the NIH and NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433 ; University of Illinois at Chicago CTSA 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 . 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.
Funding Information:
Dr Isakova received grant support from Shire and honoraria from Bayer and Eli Lilly. Dr Wolf has served as a consultant or received honoraria from Akebia, Amag, Amgen, Ardelyx, Diasorin, Japanese Torii Tobacco, Keryx, Luitpold, Sanofi, and Pharmacosmos and received grant support from Shire. The remaining authors declare that they have no relevant financial interests.
Funding Information:
Lawrence J. Appel, MD, MPH, Alan S. Go, MD, Jiang He, MD, PhD, James P. Lash, MD, Akinlolu Ojo, MD, PhD, Mahboob Rahman, MD, and Raymond R. Townsend, MD. Tamara Isakova, MD, MMSc, Xuan Cai, MS, Jungwha Lee, PhD, Rupal Mehta, MD, Xiaoming Zhang, MS, Wei Yang, PhD, Lisa Nessel, MSS, MLSP, Amanda Hyre Anderson, PhD, MPH, Joan Lo, MD, Anna Porter, MD, MS, Julie Wright Nunes, MD, MPH, Lavinia Negrea, MD, Lee Hamm, MD, Edward Horwitz, MD, Jing Chen, MD, Julia J. Scialla, MD, MHS, Ian H. de Boer, MD, MS, Mary B. Leonard, MD, MSCE, Harold I. Feldman, MD, MSCE, and Myles Wolf, MD, MMSc. Designed the study: TI, MW; collected the data: XZ, WY, AA, JC, LNessel, JLo, LH, EH, LNegrea, ML, IHdB, HIF, MW; conducted the statistical analyses: TI, XC, JLee; analyzed and interpreted the data: TI, XC, JLee, XZ, WY, RM, JJS, AA, JC, JWN, LNessel, AP, JLo, LH, EH, LNegrea, ML, IHdB, HIF, MW. 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 R01DK102438 (Dr Isakova), R01DK110087 (Dr Isakova), R01DK099199 (Dr de Boer), R01DK111952 (Dr Scialla), R01DK081374 (Dr Wolf), R01DK076116 (Dr Wolf), R01DK094796 (Dr Wolf), K24DK093723 (Dr Wolf), U01DK099930 (Drs Wolf and Isakova), and P30DK114857 from the National Institutes of Health (NIH), and a Strategically Focused Research Network Center Grant on Health Disparities from the American Heart Association (Drs Wolf and Isakova). Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work 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; Johns Hopkins University UL1 TR-000424; University of Maryland General Clinical Research Center M01 RR-16500; Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the NIH and NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433; University of Illinois at Chicago CTSA 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. 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 Isakova received grant support from Shire and honoraria from Bayer and Eli Lilly. Dr Wolf has served as a consultant or received honoraria from Akebia, Amag, Amgen, Ardelyx, Diasorin, Japanese Torii Tobacco, Keryx, Luitpold, Sanofi, and Pharmacosmos and received grant support from Shire. The remaining authors declare that they have no relevant financial interests. The authors thank the participants, investigators, and staff of the CRIC Study for their time and commitment. Received February 26, 2019. Evaluated by 3 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Robert N. Foley, MD). Accepted in revised form July 29, 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.
Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
PY - 2020/2
Y1 - 2020/2
N2 - Rationale & Objective: The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. Study Design: Retrospective analysis nested in a cohort study. Setting & Participants: Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). Exposure: Years before ESKD. Outcomes: Serial FGF-23, PTH, serum phosphate, and serum calcium levels. Analytical Approach: To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used “ESKD-anchored longitudinal analyses” to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. Results: Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. Limitations: Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Conclusions: Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.
AB - Rationale & Objective: The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. Study Design: Retrospective analysis nested in a cohort study. Setting & Participants: Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). Exposure: Years before ESKD. Outcomes: Serial FGF-23, PTH, serum phosphate, and serum calcium levels. Analytical Approach: To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used “ESKD-anchored longitudinal analyses” to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. Results: Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. Limitations: Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Conclusions: Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.
KW - CKD progression
KW - Chronic kidney disease (CKD)
KW - biomarker
KW - calcium
KW - disordered mineral metabolism
KW - end-stage renal disease (ESRD)
KW - fibroblast growth factor 23 (FGF-23)
KW - incident kidney failure
KW - kidney function
KW - longitudinal trends
KW - parathyroid hormone (PTH)
KW - phosphate
KW - serial measurements
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UR - http://www.scopus.com/inward/citedby.url?scp=85074322716&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2019.07.022
DO - 10.1053/j.ajkd.2019.07.022
M3 - Article
C2 - 31668375
AN - SCOPUS:85074322716
SN - 0272-6386
VL - 75
SP - 235
EP - 244
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -
