@article {862, title = {Cystatin C and subclinical brain infarction.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3721-7}, abstract = {

Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7\%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95\% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95\% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Brain Infarction, Confidence Intervals, Creatinine, Cross-Sectional Studies, Cystatin C, Cystatins, Disease Progression, Female, Geriatric Assessment, Humans, Incidence, Ischemic Attack, Transient, Magnetic Resonance Imaging, Male, Odds Ratio, Predictive Value of Tests, Prognosis, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Sex Factors, Survival Analysis}, issn = {1046-6673}, doi = {10.1681/ASN.2005010006}, author = {Seliger, Stephen L and Longstreth, W T and Katz, Ronit and Manolio, Teri and Fried, Linda F and Shlipak, Michael and Stehman-Breen, Catherine O and Newman, Anne and Sarnak, Mark and Gillen, Daniel L and Bleyer, Anthony and Siscovick, David S} } @article {6308, title = {Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.}, journal = {Clin J Am Soc Nephrol}, volume = {9}, year = {2014}, month = {2014 Feb}, pages = {239-46}, abstract = {

BACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.

RESULTS: The mean participant age was 78 years; 60\% of participants were women and 16\% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (>=100 RU/ml) and UACR (>=20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95\% confidence interval [95\% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95\% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95\% CI, 1.21 to 3.82).

CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.

}, keywords = {Acute Kidney Injury, Age Factors, Aged, Aged, 80 and over, Albuminuria, Biomarkers, Creatinine, Cystatin C, Female, Fibroblast Growth Factors, Glomerular Filtration Rate, Hospitalization, Humans, Independent Living, Kidney, Longitudinal Studies, Male, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors}, issn = {1555-905X}, doi = {10.2215/CJN.05830513}, author = {Brown, Jeremiah R and Katz, Ronit and Ix, Joachim H and de Boer, Ian H and Siscovick, David S and Grams, Morgan E and Shlipak, Michael and Sarnak, Mark J} } @article {6661, title = {NT-proBNP and troponin T and risk of rapid kidney function decline and incident CKD in elderly adults.}, journal = {Clin J Am Soc Nephrol}, volume = {10}, year = {2015}, month = {2015 Feb 6}, pages = {205-14}, abstract = {

BACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR>=30\%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67\% higher risk of rapid decline and 38\% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95\% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95\% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80\% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95\% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95\% confidence interval, 0.92 to 1.50).

CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.

}, keywords = {Age Factors, Aged, Aging, Biomarkers, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney, Linear Models, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Time Factors, Troponin T, United States, Up-Regulation}, issn = {1555-905X}, doi = {10.2215/CJN.04910514}, author = {Bansal, Nisha and Katz, Ronit and Dalrymple, Lorien and de Boer, Ian and DeFilippi, Christopher and Kestenbaum, Bryan and Park, Meyeon and Sarnak, Mark and Seliger, Stephen and Shlipak, Michael} }