Cystatin-C and inflammatory markers in the ambulatory elderly.
OBJECTIVE
Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels.


METHODS
This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes.


RESULTS
After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5.


CONCLUSIONS
The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.
Shlipak
Michael G
MG
General Internal Medicine Section, San Francisco Veterans Affairs Medical Center and Department of Medicine, University of California, San Francisco, Calif 94121, USA. shlip@itsa.ucsf.edu
Katz
Ronit
R
Cushman
Mary
M
Sarnak
Mark J
MJ
Stehman-Breen
Catherine
C
Psaty
Bruce M
BM
Siscovick
David
D
Tracy
Russell P
RP
Newman
Anne
A
Fried
Linda
L
D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis*; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D005340:Fibrinogen; D002097:C-Reactive Protein