Format

Send to

Choose Destination
Am J Kidney Dis. 2015 Jul;66(1):47-54. doi: 10.1053/j.ajkd.2014.11.009. Epub 2014 Dec 24.

Change in novel filtration markers and risk of ESRD.

Author information

1
Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: crebhol1@jhu.edu.
2
Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
3
Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
4
Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.

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 β2-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.

KEYWORDS:

chronic kidney disease (CKD); creatinine; cystatin C; disease progression; end-stage renal disease (ESRD); filtration marker; kidney disease outcome; surrogate endpoint; β(2)-Microglobulin (B2M)

PMID:
25542414
PMCID:
PMC4478244
DOI:
10.1053/j.ajkd.2014.11.009
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center