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Am J Kidney Dis. 2015 Jul;66(1):75-83. doi: 10.1053/j.ajkd.2015.01.013. Epub 2015 Mar 12.

Filtration markers as predictors of ESRD and mortality in Southwestern American Indians with type 2 diabetes.

Author information

1
Tufts Medical Center, Boston, MA.
2
University of California, San Francisco, San Francisco, CA.
3
University of Minnesota, Minneapolis, MN.
4
Centers for Disease Control and Prevention, Atlanta, GA.
5
Stanford University, Stanford, CA.
6
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ.
7
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
8
Boston University, Boston, MA.
9
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
10
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ. Electronic address: rnelson@nih.gov.

Abstract

BACKGROUND:

A growing number of serum filtration markers are associated with mortality and end-stage renal disease (ESRD) in adults. Whether β-trace protein (BTP) and β2-microglobulin (B2M) are associated with these outcomes in adults with type 2 diabetes is not known.

STUDY DESIGN:

Longitudinal cohort study.

SETTING & PARTICIPANTS:

250 Pima Indians with type 2 diabetes (69% women; mean age, 42 years; mean diabetes duration, 11 years).

PREDICTORS:

Serum BTP, B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or estimated using creatinine (eGFRcr) or cystatin C level (eGFRcys).

OUTCOMES & MEASUREMENTS:

Incident ESRD and all-cause mortality through December 2013. HRs were reported per interquartile range decrease of the inverse of BTP and B2M (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the addition of BTP or B2M level to established markers (eGFRcys with mGFR or eGFRcr) was evaluated using C statistics, continuous net reclassification improvement, and relative integrated discrimination improvement (RIDI).

RESULTS:

During a median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both novel markers were associated with ESRD in multivariable models. BTP level remained statistically significant after further adjustment for mGFR (1/BTP, 1.53 [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M level was associated with mortality in multivariable models and after further adjustment for mGFR (HR, 2.12; 95% CI, 1.38-3.26). The addition of B2M level to established markers increased the C statistic for mortality but only weakly when assessed by either continuous net reclassification improvement or RIDI; none was improved for ESRD by the addition of these markers.

LIMITATIONS:

Small sample size, single measurements of markers.

CONCLUSIONS:

In Pima Indians with type 2 diabetes, BTP and, to a lesser extent, B2M levels were associated with ESRD. B2M level was associated with mortality after adjustment for traditional risk factors and established filtration markers. Further studies are warranted to confirm whether inclusion of B2M level in a multimarker approach leads to improved risk prediction for mortality in this population.

KEYWORDS:

Beta-trace protein (BTP); CKD Biomarkers Consortium; Pima Indians; beta-2 microglobulin (B2M); diabetic kidney failure; end-stage renal disease (ESRD); filtration markers; glomerular filtration rate (GFR); kidney function; mortality; type 2 diabetes mellitus

PMID:
25773485
PMCID:
PMC4485524
DOI:
10.1053/j.ajkd.2015.01.013
[Indexed for MEDLINE]
Free PMC Article

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