TY - JOUR
T1 - Time-Updated Changes in Estimated GFR and Proteinuria and Major Adverse Cardiac Events
T2 - Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
AU - CRIC Study Investigators
AU - Cohen, Jordana B.
AU - Yang, Wei
AU - Li, Liang
AU - Zhang, Xiaoming
AU - Zheng, Zihe
AU - Orlandi, Paula
AU - Bansal, Nisha
AU - Deo, Rajat
AU - Lash, James P.
AU - Rahman, Mahboob
AU - He, Jiang
AU - Shafi, Tariq
AU - Chen, Jing
AU - Cohen, Debbie L.
AU - Matsushita, Kunihiro
AU - Shlipak, Michael G.
AU - Wolf, Myles
AU - Go, Alan S.
AU - Feldman, Harold I.
AU - Appel, Lawrence J.
AU - Nelson, Robert G.
AU - Rao, Panduranga S.
AU - Shah, Vallabh O.
AU - Townsend, Raymond R.
AU - Unruh, Mark L.
N1 - Funding Information:
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, U01DK060902, and U24DK060990). In addition, this work was supported in part by Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/ National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, the Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the NCATS component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131, and Department of Internal Medicine, University of New Mexico School of Medicine Albuquerque, NM R01DK119199. Dr Cohen is supported by NIH-NHLBI K23-HL133843 and R01-HL153646. Dr Shafi is supported by NIH-NHLBI R01-HL-132372 and NIH-NINR R01-NR-017399. Dr Li and Dr Yang are supported by NIH-NIDDK R01-DK-118079. The funding agencies had no role in study design, data collection, analysis, reporting, or the decision to submit the manuscript for publication.
Funding Information:
Lawrence J. Appel, MD, MPH, Robert G. Nelson, MD, PhD, MS, Panduranga S. Rao, MD, Vallabh O. Shah, PhD, MS, Raymond R. Townsend, MD, Mark L. Unruh, MD, MS. Jordana B. Cohen, MD, MSCE, Wei Yang, PhD, Liang Li, PhD, Xiaoming Zhang, MS, Zihe Zheng, MD, MHS, Paula Orlandi, MD, MSCE, Nisha Bansal, MD, MAS, Rajat Deo, MD, MTR, James P. Lash, MD, Mahboob Rahman, MD, Jiang He, MD, PhD, Tariq Shafi, MBBS, MHS, Jing Chen, MD, MMSc, MSc, Debbie L. Cohen, MD, Kunihiro Matsushita, MD, PhD, Michael G. Shlipak, MD, Myles Wolf, MD, Alan S. Go, MD, and Harold I. Feldman, MD, MSCE. Study conception/design: JBC, WY, LL, HIF; data acquisition: WY, XZ, JPL, MR, JH, JC, DLC, ASG, HIF; statistical analyses: WY, XZ; analysis interpretation: JBC, WY, XZ, LL, ZZ, PO, NB, RD, TS, KM, MGS, MW, HIF. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. 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, U01DK060902, and U24DK060990). In addition, this work was supported in part by Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, the Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the NCATS component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131, and Department of Internal Medicine, University of New Mexico School of Medicine Albuquerque, NM R01DK119199. Dr Cohen is supported by NIH-NHLBI K23-HL133843 and R01-HL153646. Dr Shafi is supported by NIH-NHLBI R01-HL-132372 and NIH-NINR R01-NR-017399. Dr Li and Dr Yang are supported by NIH-NIDDK R01-DK-118079. The funding agencies had no role in study design, data collection, analysis, reporting, or the decision to submit the manuscript for publication. The authors declare that they have no relevant financial interests. Received October 11, 2020. Evaluated by 3 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Abhijit Kshirsagar, MD, MPH). Accepted in revised form March 8, 2021. 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:
© 2021 National Kidney Foundation, Inc.
PY - 2022/1
Y1 - 2022/1
N2 - Rationale & Objective: Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk. Study Design: Prospective cohort study. Setting & Participants: Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC). Exposures: Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows. Outcomes: Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death. Analytical Approach: A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes. Results: Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19 mL/min/1.73 m2) and declining slope of eGFR (8 mL/min/1.73 m2 per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136 mg/g) and increasing UPCR (240 mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively). Limitations: Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually. Conclusions: Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.
AB - Rationale & Objective: Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk. Study Design: Prospective cohort study. Setting & Participants: Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC). Exposures: Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows. Outcomes: Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death. Analytical Approach: A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes. Results: Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19 mL/min/1.73 m2) and declining slope of eGFR (8 mL/min/1.73 m2 per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136 mg/g) and increasing UPCR (240 mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively). Limitations: Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually. Conclusions: Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.
KW - Chronic kidney disease (CKD)
KW - cardiovascular disease (CVD)
KW - cardiovascular risk
KW - eGFR slope
KW - eGFR trajectory
KW - estimated glomerular filtration rate (eGFR)
KW - heart disease
KW - heart failure
KW - landmark analysis
KW - longitudinal kidney function
KW - mortality
KW - proteinuria
KW - renal function
KW - time-updated analysis
KW - urinary protein-creatinine ratio (UPCR)
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U2 - 10.1053/j.ajkd.2021.03.021
DO - 10.1053/j.ajkd.2021.03.021
M3 - Article
C2 - 34052355
AN - SCOPUS:85111498525
VL - 79
SP - 36-44.e1
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -