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Change in novel filtration markers and risk of ESRD.

TitleChange in novel filtration markers and risk of ESRD.
Publication TypeJournal Article
Year of Publication2015
AuthorsRebholz CM, Grams ME, Matsushita K, Selvin E
Secondary AuthorsCoresh JJ
JournalAm J Kidney Dis
Volume66
Issue1
Pagination47-54
Date Published2015 Jul
ISSN1523-6838
Keywordsbeta 2-Microglobulin, Biomarkers, Comorbidity, Creatinine, Cystatin C, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Hypercholesterolemia, Hypertension, Kidney Failure, Chronic, Kidney Function Tests, Kidney Glomerulus, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Smoking, Surveys and Questionnaires, United States
Abstract

BACKGROUND: Chronic kidney disease progression is a risk factor for end-stage renal disease (ESRD). A 57% decline in creatinine-based estimated glomerular filtration rate (eGFRcr) is an established surrogate outcome for ESRD in clinical trials, and a 30% decrease recently has been proposed as a surrogate end point. However, it is unclear whether change in novel filtration marker levels provides additional information for ESRD risk to change in eGFRcr.

STUDY DESIGN: Cohort study.

SETTING & PARTICIPANTS: Atherosclerosis Risk in Communities (ARIC) Study participants from 4 US communities.

PREDICTORS: Percent change in levels of filtration markers (eGFRcr, cystatin C-based eGFR [eGFRcys], the inverse of ╬▓2-microglobulin concentration [1/B2M]) over a 6-year period.

OUTCOME: Incident ESRD.

MEASUREMENTS: Cox proportional hazards regression with adjustment for demographics, kidney disease risk factors, and first measurement of eGFRcr.

RESULTS: During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFRcr, eGFRcys, and 1/B2M were associated significantly with ESRD compared with stable concentrations of filtration markers (HRs of 19.96 [95% CI, 11.73-33.96], 16.67 [95% CI, 10.27-27.06], and 22.53 [95% CI, 13.20-38.43], respectively). Using the average of declines in the 3 markers, >30% decline conferred higher ESRD risk than that for eGFRcr alone (HR, 31.97 [95% CI, 19.40-52.70; P=0.03] vs eGFRcr).

LIMITATIONS: Measurement error could influence estimation of change in filtration marker levels.

CONCLUSIONS: A >30% decline in kidney function assessed using novel filtration markers is associated strongly with ESRD, suggesting the potential utility of measuring change in cystatin C and B2M levels in settings in which improved outcome ascertainment is needed, such as clinical trials.

DOI10.1053/j.ajkd.2014.11.009
Alternate JournalAm J Kidney Dis
PubMed ID25542414
PubMed Central IDPMC4478244
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
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS 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
HHSN268201100010C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R01 DK076770 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States