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Change in Multiple Filtration Markers and Subsequent Risk of Cardiovascular Disease and Mortality.

TitleChange in Multiple Filtration Markers and Subsequent Risk of Cardiovascular Disease and Mortality.
Publication TypeJournal Article
Year of Publication2015
AuthorsRebholz CM, Grams ME, Matsushita K, Inker LA, Foster MC, Levey AS, Selvin E
Secondary AuthorsCoresh JJ
JournalClin J Am Soc Nephrol
Volume10
Issue6
Pagination941-8
Date Published2015 Jun 05
ISSN1555-905X
Keywordsbeta 2-Microglobulin, Biomarkers, Cardiovascular Diseases, Creatinine, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States
Abstract

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.

DOI10.2215/CJN.10101014
Alternate JournalClin J Am Soc Nephrol
PubMed ID25825481
PubMed Central IDPMC4455217
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
R01DK076770 / DK / NIDDK NIH HHS / United States
T32-HL007024 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R01 DK076770 / DK / NIDDK NIH HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
K08 DK092287 / DK / NIDDK NIH HHS / United States