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Open Access Research article

Cystatin C, a novel indicator of renal function, reflects severity of cerebral microbleeds

Mi-Young Oh1, Hyon Lee1, Joon Soon Kim1, Wi-Sun Ryu2, Seung-Hoon Lee1, Sang-Bae Ko1, Chulho Kim3, Chang Hun Kim1 and Byung-Woo Yoon1*

Author Affiliations

1 Department of Neurology, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, Republic of Korea

2 Department of Neurology, Dogguk University Ilsan Hospital, Goyang, Republic of Korea

3 Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea

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BMC Neurology 2014, 14:127  doi:10.1186/1471-2377-14-127

Published: 12 June 2014

Abstract

Background

Chronic renal insufficiency, diagnosed using creatinine based estimated glomerular filtration rate (GFR) or microalbumiuria, has been associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been shown to be a more sensitive renal indicator than conventional renal markers. Under the assumption that similar pathologic mechanisms of the small vessel exist in the brain and kidney, we hypothesized that the levels of cystatin C may delineate the relationship between CMBs and renal insufficiency by detecting subclinical kidney dysfunction, which may be underestimated by other indicators, and thus reflect the severity of CMBs more accurately.

Methods

Data was prospectively collected for 683 patients with ischemic stroke. The severity of CMBs was categorized by the number of lesions. Patients were divided into quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios. Ordinal logistic regression analysis was used to examine the association of each renal indicator with CMBs.

Results

In models including both quartiles of cystatin C and estimated GFR, only cystatin C quartiles were significant (the highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI 0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and microalbumin/creatinine ratio also showed that only cystatin C quartiles was associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07-3.94; p = 0.03). These associations were also observed in the logistic models using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as continuous variables. Cystatin C was a significant indicator of deep or infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 ± 0.03; 95% CI 0.66-0.76; p = 0.02).

Conclusion

Cystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.

Keywords:
Cystatin C; Estimated glomerular filtration rate; Microalbuminuria; Cerebral microbleeds