title: Cystatin C, a novel indicator of renal function, reflects severity of cerebral microbleeds.
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).
  
  
  CONCLUSIONS
  Cystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Oh
authors.forename: Hyon
authors.initials: H
authors.lastname: Lee
authors.forename: Joon Soon
authors.initials: JS
authors.lastname: Kim
authors.forename: Wi-Sun
authors.initials: WS
authors.lastname: Ryu
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Ko
authors.forename: Chulho
authors.initials: C
authors.lastname: Kim
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, Republic of Korea. bwyoon@snu.ac.kr.
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis; D002545:Brain Ischemia / Q000097:blood / Q000150:complications; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000150:complications / Q000473:pathology*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000473:pathology; D055815:Young Adult
chemical_list: D000418:Albumins; D055316:Cystatin C; D003404:Creatinine