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Change in Multiple Filtration Markers and Subsequent Risk of Cardiovascular Disease and Mortality
Casey M Rebholz1, Morgan E Grams2, Kunihiro Matsushita3
1Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; crebhol1@jhu.edu.
Insights
Kidney disease progression, measured by declines in creatinine, cystatin C, and β2-microglobulin, significantly increases risks for cardiovascular disease and death. Monitoring these filtration markers offers crucial insights into patient prognosis.
Area of Science:
- Nephrology
- Cardiology
- Epidemiology
Background:
- Kidney disease progression is a known risk factor for cardiovascular disease (CVD) and mortality.
- Estimating glomerular filtration rate (eGFR) using creatinine is standard but may not capture the full picture of kidney function decline.
Purpose of the Study:
- To investigate the association between changes in multiple kidney filtration markers and the risk of cardiovascular events and death.
- To determine if combined changes in filtration markers provide a stronger prediction of adverse outcomes.
Main Methods:
- A cohort of 9716 participants from the Atherosclerosis Risk in Communities Study was followed from 1990-1992 to 1996-1998.
- Changes in creatinine, cystatin C, and β2-microglobulin were measured, and percentage changes in eGFR (creatinine-based), eGFR (cystatin C-based), and 1/β2-microglobulin were calculated.
- Cox regression models assessed associations between filtration marker changes and cardiovascular events/mortality up to 2011, adjusting for confounders.
Main Results:
- A decline of over 30% in any single marker (eGFRcr, eGFRcys, 1/β2M) was linked to increased mortality risk (HRs ranging from 1.91 to 2.48).
- Similar associations were observed for cardiovascular disease risk.
- An average decline of over 30% across all three markers showed a strong association with all-cause mortality (HR 2.82).
Conclusions:
- Significant kidney disease progression, indicated by a >30% decline in eGFR (creatinine or cystatin C) or 1/β2-microglobulin, is strongly associated with increased cardiovascular disease and mortality risk.
- Utilizing multiple filtration markers provides a more comprehensive assessment of kidney disease progression and its associated risks.
Background And Objectives:
Kidney disease progression, assessed by change in eGFR on the basis of creatinine, is an independent risk factor for cardiovascular disease and death. This study aimed to evaluate whether changes in multiple filtration markers, individually and combined, were associated with cardiovascular disease and death.
Design, Setting, Participants, & Measurements:
Creatinine, cystatin C, and β2-microglobulin were measured among 9716 Atherosclerosis Risk in Communities Study participants in 1990-1992 and 1996-1998. Percentage change in three filtration markers (eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/β2-microglobulin) individually and the average of percentage change across all three filtration markers were calculated. Cardiovascular events and deaths were ascertained from 1996 to 2011. Cox regression models were adjusted for established risk factors for cardiovascular disease and mortality and first measurement of eGFR on the basis of creatinine.
Results:
During a median follow-up of 14 years, there were 1922 cardiovascular events and 2285 deaths from any cause. Decline of >30% in each filtration marker was significantly associated with higher risk of mortality compared with stable kidney function (-9.9% to +9.9% change in the filtration marker) with hazard ratios (95% confidence intervals) of 1.91 (1.67 to 2.18) for eGFR on the basis of creatinine, 2.29 (1.99 to 2.63) for eGFR on the basis of cystatin C, and 2.48 (2.15 to 2.86) for 1/β2-microglobulin, with similar associations for cardiovascular disease. An average decline of >30% across the three markers was strongly associated with higher risk of all-cause mortality (hazard ratio, 2.82; 95% confidence interval, 2.42 to 3.29).
Conclusions:
Kidney disease progression was assessed using >30% decline in eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/β2-microglobulin and average decline of >30% across the three filtration markers is strongly associated with risk of cardiovascular disease and death.
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