Time-Updated Changes in Estimated GFR and Proteinuria and Major Adverse Cardiac Events: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Am J Kidney Dis. 2022 Jan;79(1):36-44.e1. doi: 10.1053/j.ajkd.2021.03.021. Epub 2021 May 28.


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 (19mL/min/1.73m2) and declining slope of eGFR (8mL/min/1.73m2 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 (136mg/g) and increasing UPCR (240mg/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.

Keywords: Chronic kidney disease (CKD); cardiovascular disease (CVD); cardiovascular risk; eGFR slope; eGFR trajectory; estimated glomerular filtration rate (eGFR); heart disease; heart failure; landmark analysis; longitudinal kidney function; mortality; proteinuria; renal function; time-updated analysis; urinary protein-creatinine ratio (UPCR).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Glomerular Filtration Rate
  • Humans
  • Prospective Studies
  • Proteinuria / diagnosis
  • Proteinuria / epidemiology
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / epidemiology
  • Risk Factors