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: 17.81). 08/2006; 145(4):237-46.
Source: PubMed


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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    • "CKD is associated with increased cardiovascular risk and mortality [1] and increased incidence of heart failure (HF). [2] Even a small reduction in kidney function is associated with higher risk of cardiovascular events and the strongest association is typically with HF. [3] Recent studies have shown an association between kidney function and HF risk across a wide spectrum of disease stages from preclinical kidney disease to advanced CKD. [4] [5] To evaluate kidney function, these studies used cystatin C. [6] The pathogenesis of HF in persons with CKD has not been well characterized but likely relates to a combination of cardiac abnormalities and volume handling. [7] Among patients without HF, kidney function has been linked with structural IJBR (2015) 6 (08) "

    08/2015; 6(8):546. DOI:10.7439/ijbr.v6i8.2358
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    • "In a population-based prospective observational cohort of 9988 individuals aged 45–64 years, cystatin C level was a much stronger predictor of all-cause mortality, coronary artery disease events, heart failure events and end-stage renal disease compared to estimates of GFR derived from CKD-EPI creatinine equation [23]. Other studies have corroborated these findings and have also shown that cystatin C level may identify the group of CKD patients that may not be identified by CKD-EPI equation as being at high risk of CVD events and all-cause mortality [24], [25]. In contrast, a recent study by Eriksen et al. has shown that cystatin C was not superior in estimating measured GFR compared to creatinine in the general population [26] and other studies have suggested that the strong association between cystatin C and CVD or all-cause mortality may be related to other factors including body size and the presence of diabetes and inflammation [27]. "
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    ABSTRACT: Background: Reduced estimated glomerular filtration rate (eGFR) using the cystatin-C derived equations might be a better predictor of cardiovascular disease (CVD) mortality compared with the creatinine-derived equations, but this association remains unclear in elderly individuals. Aim: The aims of this study were to compare the predictive values of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C eGFR equations for all-cause mortality and CVD events (hospitalizations +/- mortality). Methods: Prospective cohort study of 1165 elderly women aged. 70 years. Associations between eGFR and outcomes were examined using Cox regression analysis. Test accuracy of eGFR equations for predicting outcomes was examined using Receiver Operating Characteristic (ROC) analysis and net reclassification improvement (NRI). Results: Risk of all-cause mortality for every incremental reduction in eGFR determined using CKD-EPI-creatinine, CKD-EPI-cystatin C and the CKD-EPI-creatinine-cystatic C equations was similar. Areas under the ROC curves of CKD-EPI-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C equations for all-cause mortality were 0.604 (95%CI 0.561-0.647), 0.606 (95%CI 0.563-0.649; p = 0.963) and 0.606 (95%CI 0.563-0.649; p = 0.894) respectively. For all-cause mortality, there was no improvement in the reclassification of eGFR categories using the CKD-EPI-cystatin C (NRI -4.1%; p = 0.401) and CKD-EPI-creatinine-cystatin C (NRI -1.2%; p = 0.748) compared with CKD-EPI-creatinine equation. Similar findings were observed for CVD events. Conclusion: eGFR derived from CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C equations did not improve the accuracy or predictive ability for clinical events compared to CKD-EPI-creatinine equation in this cohort of elderly women.
    PLoS ONE 09/2014; 9(9):e106734. DOI:10.1371/journal.pone.0106734 · 3.23 Impact Factor
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    • "Cystatin C concentration is less affected by extrarenal factors compared to creatinine [12]. It has been used as a predictor of coronary heart disease, heart failure, and all causes of mortality in various populations by the detection of subclinical renal insufficiency [30-32]. Its prognostic value for adverse outcomes was independent of conventional renal parameters [31-33]. "
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    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.
    BMC Neurology 06/2014; 14(1):127. DOI:10.1186/1471-2377-14-127 · 2.04 Impact Factor
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