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eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.
Bansal N, Zelnick LR, Alonso A, Benjamin EJ, de Boer IH, Deo R, Katz R, Kestenbaum B, Mathew J, Robinson-Cohen C, Sarnak MJ, Shlipak MG, Sotoodehnia N, Young B, Heckbert SR
(2017) Clin J Am Soc Nephrol 12: 1386-1398
MeSH Terms: Adult, Aged, Aged, 80 and over, Albuminuria, Atrial Fibrillation, Biomarkers, Creatinine, Cystatin C, Disease-Free Survival, Female, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kaplan-Meier Estimate, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Myocardial Infarction, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Young Adult
Show Abstract · Added September 19, 2017
BACKGROUND AND OBJECTIVES - The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events.
RESULTS - In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and ≥300 mg/g): hazard ratios (95% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events.
CONCLUSIONS - In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.
Copyright © 2017 by the American Society of Nephrology.
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26 MeSH Terms
Galectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS).
Bansal N, Katz R, Seliger S, DeFilippi C, Sarnak MJ, Delaney JA, Christenson R, de Boer IH, Kestenbaum B, Robinson-Cohen C, Ix JH, Shlipak MG
(2016) Am J Kidney Dis 67: 994-6
MeSH Terms: Aged, Cohort Studies, Creatinine, Cystatin C, Female, Galectin 3, Glomerular Filtration Rate, Humans, Interleukin-1 Receptor-Like 1 Protein, Logistic Models, Longitudinal Studies, Male, Prognosis, Renal Insufficiency, Chronic
Added September 19, 2017
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14 MeSH Terms
Self-rated health and adverse events in CKD.
Robinson-Cohen C, Hall YN, Katz R, Rivara MB, de Boer IH, Kestenbaum BR, Himmelfarb J
(2014) Clin J Am Soc Nephrol 9: 2044-51
MeSH Terms: Acid-Base Equilibrium, Aged, Albuminuria, Area Under Curve, Biomarkers, C-Reactive Protein, Cause of Death, Creatinine, Cystatin C, Disease Progression, Female, Fibroblast Growth Factors, Follow-Up Studies, Glomerular Filtration Barrier, Health Status, Health Status Indicators, Hemoglobins, Humans, Male, Middle Aged, Parathyroid Hormone, Proportional Hazards Models, Prospective Studies, Renal Insufficiency, Chronic, Renal Replacement Therapy, Risk Factors, Sensitivity and Specificity, Uric Acid, Vitamin D
Show Abstract · Added September 19, 2017
BACKGROUND AND OBJECTIVES - Little is known about the utility of self-rated general health assessments in persons with moderate-to-severe CKD. This study examined the ability of a single self-rated health measure to predict all-cause mortality and kidney disease progression in a cohort of 443 patients with stages 3-4 CKD, recruited between 2005 and 2011, and followed until the end of 2012. The performance of models incorporating self-rated health measures was compared with previously published predictive models and more complex models comprising a multibiomarker panel.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - Participants were asked "In general, would you say your health is excellent, very good, good, fair, or poor?" Outcomes examined were time to all-cause mortality, kidney disease progression (initiation of RRT or 30% loss of eGFR), and a composite of these events. Model performances were compared using a nonparametric area under the curve (AUC) analysis.
RESULTS - Over a median follow-up of 3.3 years, 118 (27%) participants died and 138 (31%) had progression of kidney disease. Fair-to-poor self-rated health status was associated with significantly greater risks of mortality (fully adjusted hazard ratio [HR] for relative to good-to-excellent self-rated health, 2.76; 95% confidence interval [95% CI], 1.28 to 5.89), kidney disease progression (HR, 1.94; 95% CI, 1.49 to 2.56), and the combined end point (HR, 2.21; 95% CI, 1.66 to 2.96). For 3-year mortality prediction, the self-rated health model (AUC, 0.80; 95% CI, 0.76 to 0.85) had significantly higher AUCs than the base model (AUC, 0.71; 95% CI, 0.66 to 0.76) and the multibiomarker panel model (AUC, 0.74; 95% CI, 0.68 to 0.80) (P=0.03 and P=0.04, respectively).
CONCLUSIONS - A single, easily obtained measure of self-rated health helps identify patients with CKD at high risk of mortality and kidney disease progression. Routine evaluation of self-rated health may help target individuals who might benefit from more intensive monitoring strategies.
Copyright © 2014 by the American Society of Nephrology.
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29 MeSH Terms
Estimated kidney function based on serum cystatin C and risk of subsequent coronary artery calcium in young and middle-aged adults with preserved kidney function: results from the CARDIA study.
Bansal N, Vittinghoff E, Peralta CA, Shlipak MG, Grubbs V, Jacobs DR, Siscovick D, Steffes M, Carr JJ, Bibbins-Domingo K
(2013) Am J Epidemiol 178: 410-7
MeSH Terms: Adolescent, Adult, Albuminuria, Biomarkers, Calcium, Cohort Studies, Coronary Vessels, Cystatin C, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Function Tests, Male, Middle Aged, Reference Values, Risk Factors, Sensitivity and Specificity, Tomography, X-Ray Computed, Young Adult
Show Abstract · Added February 15, 2014
Whether kidney dysfunction is associated with coronary artery calcium (CAC) in young and middle-aged adults who have a cystatin C-derived estimated glomerular filtration rate (eGFRcys) greater than 60 mL/min/1.73 m(2) is unknown. In the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (recruited in 1985 and 1986 in Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California), we examined 1) the association of eGFRcys at years 10 and 15 and detectable CAC over the subsequent 5 years and 2) the association of change in eGFRcys and subsequent CAC, comparing those with stable eGFRcys to those whose eGFRcys increased (>3% annually over 5 years), declined moderately (3%-5%), or declined rapidly (>5%). Generalized estimating equation Poisson models were used, with adjustment for age, sex, race, educational level, income, family history of coronary artery disease, diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and tobacco use. Among 3,070 participants (mean age 35.6 (standard deviation, 4.1) years and mean eGFRcys 106.7 (standard deviation, 18.5) mL/min/1.73 m(2)), 529 had detectable CAC. Baseline eGFRcys was not associated with CAC. Moderate eGFRcys decline was associated with a 33% greater relative risk of subsequent CAC (95% confidence interval: 5, 68; P = 0.02), whereas rapid decline was associated with a 51% higher relative risk (95% confidence interval: 10, 208; P = 0.01) in adjusted models. In conclusion, among young and middle-aged adults with eGFRcys greater than 60 mL/min/1.73 m(2), annual decline in eGFRcys is an independent risk factor for subsequent CAC.
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20 MeSH Terms
Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function.
Siew ED, Ware LB, Bian A, Shintani A, Eden SK, Wickersham N, Cripps B, Ikizler TA
(2013) Kidney Int 84: 786-94
MeSH Terms: Acute Kidney Injury, Acute-Phase Proteins, Adult, Area Under Curve, Biomarkers, Case-Control Studies, Critical Illness, Cystatin C, Fatty Acid-Binding Proteins, Female, Glomerular Filtration Rate, Humans, Kidney, Lipocalin-2, Lipocalins, Male, Middle Aged, Prevalence, Prognosis, Proto-Oncogene Proteins, ROC Curve, Regression Analysis, Risk Factors
Show Abstract · Added August 21, 2013
The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type fatty acid-binding protein (L-FABP), and cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min per 1.73 m(2). One-hundred thirty AKI cases were identified following biomarker measurement and were compared with 250 controls without AKI. Areas under the receiver-operator characteristic curves (AUC-ROCs) for discriminating incident AKI from non-AKI were 0.58 (95% CI: 0.52-0.64), 0.59 (0.52-0.65), and 0.50 (0.48-0.57) for urine NGAL, L-FABP, and cystatin C, respectively. The combined AUC-ROC for NGAL and L-FABP was 0.59 (56-0.69). Both urine NGAL and L-FABP independently predicted AKI during multivariate regression; however, risk reclassification indices were mixed. Neither urine biomarker was independently associated with death or acute dialysis (NGAL hazard ratio 1.35 (95% CI: 0.93-1.96), L-FABP 1.15 (0.82-1.61)), although both independently predicted the need for acute dialysis alone (NGAL 3.44 (1.73-6.83), L-FABP 2.36 (1.30-4.25)). Thus, urine NGAL and L-FABP independently associated with the development of incident AKI and receipt of dialysis but exhibited poor discrimination for incident AKI using conventional definitions.
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23 MeSH Terms
Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy.
Zilinski JL, Shah RV, Gaggin HK, Gantzer ML, Wang TJ, Januzzi JL
(2012) Crit Care 16: R135
MeSH Terms: Aged, Biomarkers, Cardiac Catheterization, Cystatin C, Female, Heart Failure, Hemodynamics, Humans, Intensive Care Units, Interleukin-1 Receptor-Like 1 Protein, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Peroxidase, Prognosis, Pulmonary Artery, Receptors, Cell Surface, Troponin I
Show Abstract · Added April 15, 2014
INTRODUCTION - This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy.
METHODS - Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant).
RESULTS - Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01).
CONCLUSIONS - In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients.
TRIAL REGISTRATION - ClinicalTrials.gov Identifier: NCT00595738.
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18 MeSH Terms
Update on acute kidney injury after cardiac surgery.
Shaw A
(2012) J Thorac Cardiovasc Surg 143: 676-81
MeSH Terms: Acute Kidney Injury, Acute-Phase Proteins, Biomarkers, Cardiac Surgical Procedures, Creatinine, Cystatin C, Evidence-Based Medicine, Hepatitis A Virus Cellular Receptor 1, Humans, Lipocalin-2, Lipocalins, Membrane Glycoproteins, Predictive Value of Tests, Proto-Oncogene Proteins, Receptors, Virus, Treatment Outcome, Urination
Show Abstract · Added October 20, 2015
OBJECTIVES - To review the current state of clinical practice and discuss recent advances in the diagnosis and management of acute kidney injury (AKI) in the context of cardiac surgery.
METHODS - A review of the published data pertaining to AKI in the setting of cardiac surgery and cardiothoracic surgical critical care medicine was conducted, and the relevant data were synthesized from appropriate interventional and observational study reports.
RESULTS - Significant advances have occurred in the diagnosis of AKI, and consensus has been reported on a system of diagnosis using the serum creatinine and urine output. New biomarkers of injury and function are available that are likely to improve the interval to diagnosis of AKI after cardiac surgery. The adverse effect on outcome of small changes in serum creatinine is appreciated. Novel prevention and rescue therapies are now entering phase I and II studies. Urinary alkalinization was effective in a phase II blinded clinical trial and is now the subject of a multicenter, double-blind, randomized clinical trial of cardiac surgery patients.
CONCLUSIONS - In 2011, the field of AKI could be emerging from a period of stagnation that has lasted more than 2 decades. The failure to translate successful animal model interventions to the clinic might have resulted from delays in diagnosis that might now be avoidable with the advent of novel diagnostic biomarkers.
Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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17 MeSH Terms
Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus.
Lertnawapan R, Bian A, Rho YH, Raggi P, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM
(2012) Lupus 21: 279-87
MeSH Terms: Adult, Blood Sedimentation, Calcium, Case-Control Studies, Coronary Artery Disease, Cross-Sectional Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Inflammation, Kidney Diseases, Logistic Models, Lupus Erythematosus, Systemic, Male, Middle Aged
Show Abstract · Added December 10, 2013
BACKGROUND - Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis.
METHODS - Serum cystatin C, creatinine, tumor necrosis factor (TNF)-α, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models.
RESULTS - Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-α (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99).
CONCLUSIONS - Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.
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16 MeSH Terms
Pyridorin in type 2 diabetic nephropathy.
Lewis EJ, Greene T, Spitalewiz S, Blumenthal S, Berl T, Hunsicker LG, Pohl MA, Rohde RD, Raz I, Yerushalmy Y, Yagil Y, Herskovits T, Atkins RC, Reutens AT, Packham DK, Lewis JB, Collaborative Study Group
(2012) J Am Soc Nephrol 23: 131-6
MeSH Terms: Aged, Creatinine, Cystatin C, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Proteinuria, Pyridoxal Phosphate, Pyridoxamine
Show Abstract · Added December 10, 2013
Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls, but whether these actions translate into renoprotective effects is unknown. In this double-blind, randomized, placebo-controlled trial, we randomly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo; Pyridorin, 150 mg twice daily; or Pyridorin, 300 mg twice daily, for 52 weeks. At baseline, the mean age ± SD was 63.9±9.5 years, and the mean duration of diabetes was 17.6±8.5 years; the mean serum creatinine level was 2.2±0.6 mg/dl, and the mean protein-to-creatinine ratio was 2973±1932 mg/g. Regarding the primary end point, a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo. However, analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function. Among patients in the lowest tertile of baseline serum creatinine concentration, treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks (0.28, 0.07, and 0.14 mg/dl for placebo, Pyridorin 150 mg, and Pyridorin 300 mg, respectively; P=0.05 for either Pyridorin dose versus placebo); there was no evidence of a significant treatment effect in the middle or upper tertiles. In conclusion, this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year, although it suggests that patients with less renal impairment might benefit.
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14 MeSH Terms
Cystatin C, renal function, and atherosclerosis in rheumatoid arthritis.
Lertnawapan R, Bian A, Rho YH, Kawai VK, Raggi P, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM
(2011) J Rheumatol 38: 2297-300
MeSH Terms: Adult, Aged, Arthritis, Rheumatoid, Biomarkers, Calcium, Case-Control Studies, Coronary Artery Disease, Coronary Vessels, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, Interleukin-6, Kidney, Male, Middle Aged, Risk Factors, Tumor Necrosis Factor-alpha
Show Abstract · Added December 10, 2013
OBJECTIVE - We examined the hypothesis that cystatin C, a novel marker of renal function, is elevated in rheumatoid arthritis (RA) and is associated with inflammation and coronary atherosclerosis.
METHODS - We measured serum cystatin C, creatinine, tumor necrosis factor-α and interleukin 6 concentrations, coronary artery calcium score (CACS), and Modified Diet in Renal Disease estimated glomerular filtration rate in 167 patients with RA and 91 controls.
RESULTS - Cystatin C was higher in RA patients [median (IQR) 1.16 (0.99-1.35) mg/l] than controls [1.01 (0.90-1.19) mg/l; p < 0.001] and correlated positively with erythrocyte sedimentation rate (p < 0.001), C-reactive protein (p = 0.01), 28-joint Disease Activity Score (p = 0.006), and Framingham risk score (FRS; p = 0.02). Cystatin C was correlated with CACS (p < 0.001) in RA, but this was not significant after adjustment for age, race, sex, and FRS (p = 0.44).
CONCLUSION - Cystatin C concentrations are higher in RA than controls and may reflect inflammation and undetected subclinical renal dysfunction. Cystatin C provides information regarding the risk of atherosclerosis in RA, but this is not independent of the information provided by conventional cardiovascular risk factors.
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19 MeSH Terms