Faculty Bibliography

BACKGROUND:Despite interest in the importance of the home food environment and its potential influence on children's diets and social norms, there remain few self-report checklist methods that have been validated against the gold standard of researcher-conducted inventories. This study aimed to assess the criterion validity and reliability of the 'Home Food Availability Inventory Checklist' (HFAI-C), a 39-item checklist including categories of fruit, vegetables, snacks and drinks. METHODS:The HFAI-C was completed by 97 participants of White and Pakistani origin in the UK. Validity was determined by comparing participant-reported HFAI-C responses to data from researcher observations of home food availability using PABAK and weighted kappa statistics. The validity of measuring the amount of items (in addition to presence/absence) available was also determined. Test-retest reliability compared repeated administrations of the HFAI-C using intra-class correlation coefficients. RESULTS:Validity and reliability was fair to moderate overall. For validity, the average category-level PABAK ranged from 0.31 (95% CI: 0.25, 0.37) for vegetables to 0.44 (95% CI: 0.40, 0.49) for fruits. Assessment of the presence/absence of items demonstrated higher validity compared to quantity measurements. Reliability was increased when the HFAI-C was repeated close to the time of the first administration. For example, ICCs for reliability of the measurement of fruits were 0.52 (95%CI: 0.47, 0.56) if re-administered within 5 months, 0.58 (95% CI: 0.51, 0.64) within 30 days and 0.97 (95%CI: 0.94, 1.00) if re-administered on the same day. CONCLUSIONS:Overall, the HFAI-C demonstrated fair to moderate validity and reliability in a population of White and South Asian participants. This evaluation is consistent with previous work on other checklists in less diverse, more affluent populations. Our research supports the use of the HFAI-C as a useful, albeit imperfect, representation of researcher-conducted inventories. The feasibility of collecting information using the HFAI-C in large, multi-ethnic samples can facilitate examination of home food availability in relation to exposures such as ethnicity and outcomes including behavioural, social and health outcomes. Future work using the HFAI-C could provide important insights into a modifiable influence with potential to impact health.

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

BACKGROUND:Management trends in early chronic kidney disease (CKD) and their associations with clinical outcomes have not previously been reported. METHODS:We evaluated incident (Stage G3A) CKD patients from an integrated health care system in 2004-06, 2007-09 and 2010-12 to determine adjusted trends in screening (urinary protein quantification), treatment [prescription for angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and statin] and nephrology referral. For the same time periods, adjusted rates for mortality, progression to Stage G4 CKD and hospitalization for myocardial infarction or heart failure were calculated and compared across time periods. RESULTS:There were 728, 788 and 956 patients with incident CKD in 2004-06, 2007-09 and 2010-12, respectively. Adjusted rates of proteinuria quantification (31, 39 and 51 screens/100 person-years), statin prescription (53, 63 and 64 prescriptions/100 person-years) and nephrology referral (2, 3 and 5 referrals/100 person-years) all increased over time (P for trend <0.001 in all cases). ACEI/ARB prescription rates did not change (88, 83 and 80 prescriptions/100 person-years, P = 0.68). Adjusted death rates (7, 5 and 6 deaths/100 person-years), CKD progression (9, 10 and 7 progressors/100 person-years) and cardiovascular hospitalization (10, 8 and 9 hospitalizations per 100/person-years) did not change (P for trend >0.4 in all cases). CONCLUSION/CONCLUSIONS:In this integrated health care system, management of incident CKD over the past decade has intensified.

BACKGROUND:Extreme values that arise for any reason, including those through nonlaboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers. METHODS:We previously identified substantial laboratory drift in uric acid measurements in the Atherosclerosis Risk in Communities (ARIC) Study over time. Serum uric acid was originally measured in 1990-1992 on a Coulter DACOS instrument using an uricase-based measurement procedure. To recalibrate previous measured concentrations to a newer enzymatic colorimetric measurement procedure, uric acid was remeasured in 200 participants from stored plasma in 2011-2013 on a Beckman Olympus 480 autoanalyzer. To conduct IOR, we excluded data points >3 SDs from the mean difference. We continued this process using the resulting data until no outliers remained. RESULTS:IOR detected more outliers and yielded greater precision in simulation. The original mean difference (SD) in uric acid was 1.25 (0.62) mg/dL. After 4 iterations, 9 outliers were excluded, and the mean difference (SD) was 1.23 (0.45) mg/dL. Conducting only one round of outlier removal (standard approach) would have excluded 4 outliers [mean difference (SD) = 1.22 (0.51) mg/dL]. Applying the recalibration (derived from Deming regression) from each approach to the original measurements, the prevalence of hyperuricemia (>7 mg/dL) was 28.5% before IOR and 8.5% after IOR. CONCLUSIONS:IOR is a useful method for removal of extreme outliers irrelevant to recalibrating laboratory measurements, and identifies more extraneous outliers than the standard approach.

BACKGROUND:The link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear. METHODS:We studied 367,932 adults (20-93 years old) in the Korean Heart Study (baseline between 1996-2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders. RESULTS:Although cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73 m2 and 54.3% for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73 m2) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24-1.78]) and non-CVD/non-cancer causes (1.78 [1.54-2.05]). The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73 m2 when eGFR 45-59 ml/min/1.73 m2 was set as a reference (1.62 [1.10-2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66-2.25]), cancer (1.49 [1.32-1.68]), and other causes (2.19 [1.96-2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis. CONCLUSION/CONCLUSIONS:Low eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.

BACKGROUND:Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. METHODS:We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. RESULTS:Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). CONCLUSIONS:Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context.

BACKGROUND:Evaluation of candidates to serve as living kidney donors relies on screening for individual risk factors for end-stage renal disease (ESRD). To support an empirical approach to donor selection, we developed a tool that simultaneously incorporates multiple health characteristics to estimate a person's probable long-term risk of ESRD if that person does not donate a kidney. METHODS:We used risk associations from a meta-analysis of seven general population cohorts, calibrated to the population-level incidence of ESRD and mortality in the United States, to project the estimated long-term incidence of ESRD among persons who do not donate a kidney, according to 10 demographic and health characteristics. We then compared 15-year projections with the observed risk among 52,998 living kidney donors in the United States. RESULTS:A total of 4,933,314 participants from seven cohorts were followed for a median of 4 to 16 years. For a 40-year-old person with health characteristics that were similar to those of age-matched kidney donors, the 15-year projections of the risk of ESRD in the absence of donation varied according to race and sex; the risk was 0.24% among black men, 0.15% among black women, 0.06% among white men, and 0.04% among white women. Risk projections were higher in the presence of a lower estimated glomerular filtration rate, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. In the model-based lifetime projections, the risk of ESRD was highest among persons in the youngest age group, particularly among young blacks. The 15-year observed risks after donation among kidney donors in the United States were 3.5 to 5.3 times as high as the projected risks in the absence of donation. CONCLUSIONS:Multiple demographic and health characteristics may be used together to estimate the projected long-term risk of ESRD among living kidney-donor candidates and to inform acceptance criteria for kidney donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

BACKGROUND:Disordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies. STUDY DESIGN/METHODS:Nested case-control study. SETTING & PARTICIPANTS/METHODS:Middle-aged black and white men and women from 4 US communities. PREDICTORS/METHODS:Baseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (1996-1998) of the ARIC (Atherosclerosis Risk in Communities) Study. OUTCOME/RESULTS:ESRD cases (n=184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n=251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race. MEASUREMENTS/METHODS:Logistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone. RESULTS:Higher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76; 95% CI, 1.22-2.54; P=0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P=0.02] and 0.63 [95% CI, 0.43-0.91; P=0.02] for free and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D (OR, 0.83; 95% CI, 0.58-1.19; P=0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P=0.2). LIMITATIONS/CONCLUSIONS:Lack of direct measurement of free and bioavailable vitamin D. CONCLUSIONS:In the general population, blood levels of vitamin D binding protein were positively associated and blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.

OBJECTIVE:We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. RESEARCH DESIGN AND METHODS:We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. RESULTS:Median values of biomarkers were higher among blacks versus whites (all P < 0.001). Relative risks for each biomarker with incident CVD and ESRD, and odds ratios for each biomarker with prevalent retinopathy, were similar by race (all P values for interaction by race >0.10). CONCLUSIONS:The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications.