Change in novel filtration markers and risk of ESRD.

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.

• Authors: Casey M Rebholz, Morgan E Grams, Kunihiro Matsushita, Elizabeth Selvin, Josef Coresh
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 66 Issue 1 Pg. 47-54 (Jul 2015) ISSN: 1523-6838 [Electronic] United States
• PMID: 25542414 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cystatin C
• beta 2-Microglobulin
• Creatinine

Topics

• Biomarkers
• Comorbidity
• Creatinine (blood)
• Cystatin C (blood)
• Disease Progression
• Female
• Follow-Up Studies
• Glomerular Filtration Rate
• Humans
• Hypercholesterolemia (epidemiology)
• Hypertension (epidemiology)
• Kidney Failure, Chronic (epidemiology, etiology)
• Kidney Function Tests (methods)
• Kidney Glomerulus (physiopathology)
• Male
• Middle Aged
• Proportional Hazards Models
• Prospective Studies
• Renal Insufficiency, Chronic (blood, complications, epidemiology, physiopathology)
• Risk Factors
• Smoking (epidemiology)
• Surveys and Questionnaires
• United States (epidemiology)
• beta 2-Microglobulin (analysis)