Original Investigation
Pathogenesis and Treatment of Kidney Disease
Cystatin C and Albuminuria as Risk Factors for Development of CKD Stage 3: The Multi-Ethnic Study of Atherosclerosis (MESA)

https://doi.org/10.1053/j.ajkd.2010.11.021Get rights and content

Background

The growing burden and morbidity of chronic kidney disease (CKD) warrant effective strategies for identifying those at increased risk. We examined the association of cystatin C level and albuminuria with the development of CKD stage 3.

Study Design

Prospective observational study.

Setting & Participants

5,422 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2.

Predictor

Participants were categorized into 4 mutually exclusive groups: the presence or absence of microalbuminuria (albumin-creatinine ratio >17 and >25 μg/mg in men and women, respectively) in those with or without cystatin C level ≥1.0 mg/L.

Outcomes & Measurements

Incident CKD stage 3 was defined as eGFR <60 mL/min/1.73 m2 at the third or fourth visit and an annual decrease >1 mL/min/1.73 m2. Poisson regression was used to evaluate incident rate ratios in unadjusted and adjusted analyses that include baseline eGFR.

Results

Mean age was 61 years, 49% were men, 38% were white, 11% had diabetes, 13.7% had cystatin C level ≥1 mg/L, 8.4% had microalbuminuria, and 2.7% had cystatin C level ≥1 mg/L with microalbuminuria. 554 (10%) participants developed CKD stage 3 during a median follow-up of 4.7 years, and adjusted incidence rate ratios were 1.57 (95% CI, 1.19-2.07), 1.37 (95% CI, 1.13-1.66), and 2.12 (95% CI, 1.61-2.80) in those with microalbuminuria, cystatin C level ≥1 mg/L, and both, respectively, compared with those with neither.

Limitations

Relatively short follow-up and absence of measured GFR.

Conclusions

Cystatin C level and microalbuminuria are independent risk factors for incident CKD stage 3 and could be useful as screening tools to identify those at increased risk.

Section snippets

Study Population

MESA is a population study of community-dwelling adults aged 45-84 years and was designed to determine the characteristics of subclinical CVD and its progression. From 2000 to 2002, a total of 6,814 adults were recruited from 6 US communities (Baltimore, MD; Chicago, IL; Forsyth County, NC; Los Angeles, CA; northern Manhattan, NY; and St. Paul, MN). Sampling and recruitment procedures have been described in detail elsewhere.29 Individuals with symptoms or history of medical or surgical

Characteristics of Study Participants

Of 6,814 MESA participants, 1,392 were excluded, resulting in a sample of 5,422 for analysis. Of these, 4,888 participants (90%) had creatinine measured at the third and fourth visit. Participants who were excluded for missing creatinine values at follow-up were older; had a higher baseline prevalence of diabetes and hypertension; higher triglyceride, C-reactive protein, and ACR values; and lower eGFRs compared with participants included in the analysis (data not shown).

Included participants

Discussion

In this analysis, we show that higher serum cystatin C level and microalbuminuria are associated independently with incident CKD stage 3 in a large representative multiethnic cohort. Risks of incident CKD stage 3 associated with increased cystatin C level and microalbuminuria were independent of each other and baseline eGFR, and there was no statistically significant interaction between the 2 variables. Furthermore, there was no overt difference in these relationships among groups based on

Acknowledgements

The authors thank the other investigators, staff, and participants of MESA for their valuable contributions. A full list of participating MESA investigators and institutions can be found at www.mesa-nhlbi.org.

Support: The study was funded by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute, which had a role in study design and data collection, and National Institute of Diabetes and Digestive and Kidney Diseases grant K24 078204.

Financial Disclosure:

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    Originally published online February 7, 2011.

    Because a quorum could not be reached after those editors with potential conflicts recused themselves from consideration of this manuscript, the peer-review and decision-making processes were handled entirely by an Associate Editor (Mark M. Mitsnefes, MD, Cincinnati Children's Hospital Medical Center) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

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    Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.