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Shlipak, M. G. et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann. Intern. Med. 145, 237-246

San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California 94121, USA.
Annals of internal medicine (Impact Factor: 16.1). 08/2006; 145(4):237-46.
Source: PubMed

ABSTRACT Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).
To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.
Cohort study.
The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.
4663 elderly persons.
Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).
At baseline, 78% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.
Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.
Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.

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    • "Other factors reflecting kidney function are the levels of serum cystatin C and urinary albumin excretion. Evaluations of serum cystatin C and serum creatinine were reported to predict cardiovascular events in elderly persons without chronic kidney disease [6]. In addition, urinary albumin excretion is a predictor of all causes of mortality in the general population [7]. "
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    • "However, despite initial optimism that cystatin C might be a more sensitive marker of GFR than creatinine, especially for the detection of mild decrements in renal function [8], there remains no definitive evidence that cystatin C-based estimates of GFR (eGFR CysC ) are superior to eGFR Cr as an indicator of measured GFR in the general population [9] [10]. Yet, compared to eGFR Cr, eGFR CysC has consistently demonstrated a stronger and more linear association with hard outcomes such as all-cause mortality, cardiovascular mortality, and cardiovascular events [11] [12]. Moreover, in recent analysis of 816 participants from the Modification of Diet in Renal Disease study (mean age 52 AE 12 years; mean eGFR Cr 33 AE 11 mL/ min/1.73 "
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    • "More sensitive methods can detect low levels of hsCRP which are needed for the prediction of cardiovascular risk. Blood hsCRP levels may be decreased due to antiinflammatory treatment or the use of statins and increase in patients with chronic inflammation (Shlipak et al., 2006). Adiponectin corresponds to 0.01% of total plasma proteins. "
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