@article {1148, title = {Physical activity and rapid decline in kidney function among older adults.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Dec 14}, pages = {2116-23}, abstract = {

BACKGROUND: Habitual physical activity (PA) has both physiologic and metabolic effects that may moderate the risk of kidney function decline. We tested the hypothesis that higher levels of PA are associated with a lower risk of kidney function decline using longitudinal data from a large cohort of older adults.

METHODS: We studied 4011 ambulatory participants aged 65 or older from the Cardiovascular Health Study (CHS) who completed at least 2 measurements of kidney function over 7 years. We calculated a PA score (range, 2-8) by summing kilocalories expended per week (ordinal score of 1-5 from quintiles of kilocalories per week) and walking pace (ordinal score for categories of <2, 2-3, and >3 mph). Rapid decline in kidney function decline (RDKF) was defined by loss of more than 3.0 mL/min/1.73 m(2) per year in glomerular filtration rate, which we estimated by using longitudinal measurements of cystatin C levels.

RESULTS: A total of 958 participants had RDKF (23.9\%; 4.1 events per 100 person-years). The estimated risk of RDKF was 16\% in the highest PA group (score of 8) and 30\% in the lowest PA group (score of 2). After multivariate adjustment, we found that the 2 highest PA groups (scores of 7-8) were associated with a 28\% lower risk of RDKF (95\% confidence interval, 21\%-41\% lower risk) than the 2 lowest PA groups (score of 2-3). Greater kilocalories of leisure-time PA and walking pace were also each associated with a lower incidence of RDKF.

CONCLUSION: Higher levels of PA are associated with a lower risk of RDKF among older adults.

}, keywords = {Aged, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Motor Activity, Renal Insufficiency, Time Factors}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.438}, author = {Robinson-Cohen, Cassianne and Katz, Ronit and Mozaffarian, Dariush and Dalrymple, Lorien S and de Boer, Ian and Sarnak, Mark and Shlipak, Mike and Siscovick, David and Kestenbaum, Bryan} } @article {1256, title = {Cystatin C identifies chronic kidney disease patients at higher risk for complications.}, journal = {J Am Soc Nephrol}, volume = {22}, year = {2011}, month = {2011 Jan}, pages = {147-55}, abstract = {

Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR <60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9\% had CKD by the creatinine-based equation only, 2\% had CKD by the cystatin C-based equation only, and 4\% had CKD by both equations; in CHS, these percentages were 12, 4, and 13\%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95\% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95\% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95\% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95\% CI 0.98 to 1.21), 1.78 (95\% CI 1.53 to 2.08), and 1.74 (95\% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Chronic Disease, Creatinine, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Heart Failure, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Risk Factors}, issn = {1533-3450}, doi = {10.1681/ASN.2010050483}, author = {Peralta, Carmen A and Katz, Ronit and Sarnak, Mark J and Ix, Joachim and Fried, Linda F and de Boer, Ian and Palmas, Walter and Siscovick, David and Levey, Andrew S and Shlipak, Michael G} } @article {1329, title = {Vitamin D, parathyroid hormone, and cardiovascular events among older adults.}, journal = {J Am Coll Cardiol}, volume = {58}, year = {2011}, month = {2011 Sep 27}, pages = {1433-41}, abstract = {

OBJECTIVES: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study).

BACKGROUND: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health.

METHODS: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality.

RESULTS: There were 384 participants (17\%) with serum 25-OHD concentrations <15 ng/ml and 570 (25\%) with serum PTH concentrations >= 65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9\% greater (95\% confidence interval [CI]: 2\% to 17\% greater) relative hazard of mortality and a 25\% greater (95\% CI: 8\% to 44\% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29\% greater (95\% CI: 5\% to 55\% greater) risk for mortality. Serum PTH concentrations >= 65 pg/ml were associated with a 30\% greater risk for heart failure (95\% CI: 6\% to 61\% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events.

CONCLUSIONS: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Parathyroid Hormone, Prospective Studies, Vitamin D}, issn = {1558-3597}, doi = {10.1016/j.jacc.2011.03.069}, author = {Kestenbaum, Bryan and Katz, Ronit and de Boer, Ian and Hoofnagle, Andy and Sarnak, Mark J and Shlipak, Michael G and Jenny, Nancy S and Siscovick, David S} } @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} } @article {9254, title = {Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.}, journal = {Diabetes}, volume = {71}, year = {2022}, month = {2022 Dec 01}, pages = {2664-2676}, abstract = {

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40\% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD.

}, keywords = {Angiopoietin-1, Angiopoietin-2, Angiopoietins, Biomarkers, Cohort Studies, Diabetes Mellitus, Diabetic Nephropathies, Disease Progression, Endothelial Cells, Humans, Kidney Failure, Chronic, Receptor, TIE-2, Signal Transduction}, issn = {1939-327X}, doi = {10.2337/db22-0169}, author = {Liu, Jiahao and Nair, Viji and Zhao, Yi-Yang and Chang, Dong-Yuan and Limonte, Christine and Bansal, Nisha and Fermin, Damian and Eichinger, Felix and Tanner, Emily C and Bellovich, Keith A and Steigerwalt, Susan and Bhat, Zeenat and Hawkins, Jennifer J and Subramanian, Lalita and Rosas, Sylvia E and Sedor, John R and Vasquez, Miguel A and Waikar, Sushrut S and Bitzer, Markus and Pennathur, Subramaniam and Brosius, Frank C and de Boer, Ian and Chen, Min and Kretzler, Matthias and Ju, Wenjun} }