Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys Ͻ60 ml/min per 1.73 m 2 and a decline in eGFRcys Ն1 ml/min per year. Among participants with eGFRcreat Ͼ60 ml/min per 1.73 m 2 at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m 2 /yr faster on average, P ϭ 0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m 2 /yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities.

Objective. To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality.Design. Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25-hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated.Subjects. Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994.Results. 25-Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng mL, was associated with a 3.7-fold increase in the odds of frailty amongst whites and a fourfold increase in the odds of frailty amongst non-whites. This association persisted after sensitivity analyses adjusting for season of the year and latitude of residence, intended to reduce misclassification of persons as 25-hydroxyvitamin D deficient or insufficient.Conclusion. Low serum 25-hydroxyvitamin D concentrations are associated with frailty amongst older adults.

Microalbuminuria is a common condition associated with increased incidence of cardiovascular events and mortality. Abdominal obesity is associated with microalbuminuria, but studies linking visceral adipose tissue (VAT) and microalbuminuria are limited. Our objective was to determine the associations of albuminuria with VAT and subcutaneous adipose tissue (SAT). We performed a cross‐sectional study in the Framingham Multi‐Detector Computed Tomography (MDCT) cohort (n = 3,099, 48.2% women, mean age 53 years). VAT and SAT volumes were measured using computed tomography. Urinary albumin‐to‐creatinine ratio (UACR) was calculated from spot urine samples. Microalbuminuria was defined as a UACR >25 mg/g in women or >17 mg/g in men. Overall, 7.9% (n = 244) of the sample had microalbuminuria. Among men, VAT (odds ratio (OR) 1.48 per s.d., P < 0.0001) and SAT (OR 1.37 per s.d., P = 0.0002) were associated with microalbuminuria in minimally adjusted models, which remained significant after multivariable adjustment (VAT OR 1.34 per s.d., P = 0.001; SAT OR 1.28 per s.d., P = 0.005). Additionally, when considered jointly, VAT (P = 0.002) but not SAT (P = 0.2) was associated with microalbuminuria. In women, VAT was associated with microalbuminuria after minimal adjustment (OR 1.28, P = 0.01), but not after multivariable adjustment (OR 1.03, P = 0.8). In multivariable models in women, SAT was associated with a decreased odds of having microalbuminuria (OR 0.75 per s.d., P = 0.03). In conclusion, VAT is associated with microalbuminuria in men but not women. Albuminuria may be a manifestation of visceral adiposity.

In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life.

Background Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval &gt;200 ms, QRS interval &gt;100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08–1.40]}, QRS [OR 1.28 (95% CI 1.16–1.42)] and QTc [OR 1.94 (95% CI 1.50–2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06–1.16)] and QTc [OR 1.82 (95% CI 1.58–2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

Background: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs. Methods: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis. Results: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%–41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery. Conclusions: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes.

Background: Whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂) levels are associated with kidney function decline has not been well studied. Methods: We investigated associations of Lp-PLA₂ antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≧3 ml/min/1.73 m² per year. We stratified by baseline preserved GFR (≧60 ml/min/1.73 m²). Results: Mean age was 72 ± 5 years. Average eGFRcys decline was –1.79 ml/min/1.73 m² (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA₂ antigen, eGFRcys decline was faster among persons in the second, β –0.31 (95% CI –0.52, –0.10), third –0.19 (–0.41, 0.02) and fourth quartiles –0.26 (–0.48, –0.04) after full adjustment. Persons in the highest quartile of Lp-PLA₂ antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA₂ activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m²) at baseline. Conclusion: Higher levels of Lp-PLA₂ antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.

Type 1 diabetes (T1D) is associated with lower bone mineral density (BMD) and elevated fracture risk. In this study, we examined risk factors for lower BMD in the DCCT/EDIC study, a well-characterized cohort of older adults with T1D. Dual x-ray absorptiometry (DXA) scans were obtained in 1,058 study participants who had been followed for &gt; 30 years. Cumulative glycemic control was defined as the time-weighted mean HbA1c from DCCT baseline (1983-1989) to the DXA visit. Levels of advanced glycation endproducts (AGE) were assessed by skin intrinsic fluorescence (SIF) in 2010-2011. Kidney disease (sustained eGFR&lt;60 mL/min/1.73 m2 or ESRD), retinopathy, peripheral neuropathy and cardiac autonomic neuropathy were assessed. Associations between risk factors and total hip and femoral neck BMD were analyzed using multiple linear regression models. Mean age at DXA was 59±7 years; 48% of participants were female. Mean BMD for total hip and femoral neck was 0.921±0.149 and 0.757±0.129 g/cm2, respectively; 6% were osteoporotic, and 45% were osteopenic. Higher mean HbA1c, higher SIF, and kidney disease, but not retinopathy or neuropathy, were independently associated with lower BMD at the total hip in univariate and multivariable analyses, with similar results for femoral neck (Table). In conclusion, poorer glycemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with T1D. Disclosure A.V. Schwartz: None. J.C. Backlund: None. I. deBoer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; George Clinical, Goldfinch Bio, Ironwood Pharmaceuticals. M. Rubin: Research Support; Self; Amgen, Ascendis Pharma, Takeda Pharmaceutical Company Limited. A.R. Barnie: None. K. Farrell: Stock/Shareholder; Spouse/Partner; Dexcom, Inc., Tandem Diabetes Care. V.R. Trapani: None. N.S. Gregory: None. A. Wallia: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., UnitedHealth Group. J.M. Lachin: Board Member; Self; Tolerion, Inc. B.H. Braffett: None. R. Gubitosi-Klug: None. Funding National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Disease (5U01DK094157, RES514948)