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1.  APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease 
The New England journal of medicine  2013;369(23):2183-2196.
BACKGROUND
Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.
METHODS
In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.
RESULTS
In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).
CONCLUSIONS
Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)
doi:10.1056/NEJMoa1310345
PMCID: PMC3969022  PMID: 24206458
2.  Retinopathy and Cognitive Impairment in Adults With CKD 
Background
Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small vessel disease. This relationship has not been evaluated among persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment.
Study Design
Cross-sectional study
Setting & Participants
588 participants ≥ 52 years old with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study
Predictor
Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels.
Outcomes
Neuropsychological battery of six cognitive tests
Measurements
Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy adjusting for age, race, sex, education, and medical comorbidities.
Results
The mean age of the cohort was 65.3 +/− 5.6 (SD) years; 51.9% were non-White, and 52.6% were male. The prevalence of retinopathy was 30.1% and 14.3% for cognitive impairment. Compared to those without retinopathy, participants with retinopathy had increased likelihood of cognitive impairment on executive function (35.1% vs. 11.5%; OR, 3.4; 95% CI, 2.0-6.0), attention (26.7% vs. 7.3%; OR, 3.0; 95% CI, 1.8-4.9), and naming (26.0% vs. 10.0%; OR, 2.1; 95% CI, 1.2-3.4) after multivariable adjustment. Increased level of retinopathy was also associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment.
Limitations
Unknown temporal relationship between retinopathy and impairment.
Conclusions
In adults with CKD, retinopathy is associated with poor performance on several cognitive domains including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.
doi:10.1053/j.ajkd.2012.10.006
PMCID: PMC4030670  PMID: 23206534
3.  Factors Associated with Total Inpatient Costs and Length of Stay among Veterans with Lower Extremity Amputation during the Surgical Hospitalization 
Objective
To identify patient- and facility-level factors associated with total inpatient costs and length of stay (LOS) among veterans with lower extremity amputation.
Design
Patient data for 1,536 veterans were compiled from 9 databases from the Veterans Health Administration between October 1, 2002, and September 30, 2003. Linear mixed models were used to identify factors associated with the natural logarithm of total inpatient costs and LOS.
Results
Statistically significant factors associated with both higher total inpatient costs and longer LOS included admission by transfer from another hospital, systemic sepsis, arrhythmias, chronic blood loss anemia, fluid and electrolyte disorders, weight loss, specialized inpatient rehabilitation, and larger hospital bed sizes. Device infection, coagulopathy, solid tumor without metastasis, CARF accreditation, and Medicare Wage Index were only associated with higher total inpatient costs. Factors only associated with longer LOS included older age, not being married, previous amputation complication, congestive heart failure, deficiency anemias, and paralysis.
Conclusions
Most drivers of total inpatient costs were similar to those that increased LOS with a few exceptions. These findings may have implications for projecting future health care costs, and thus could be important in efforts to reducing costs, understanding LOS, and refining payment and budgeting policies.
doi:10.1097/PHM.0b013e31827446eb
PMCID: PMC3601547  PMID: 23117271
Health Care Costs; Length of Stay; Rehabilitation; Amputation; Inpatient
4.  Fibroblast growth factor 23 is not associated with and does not induce arterial calcification 
Kidney international  2013;83(6):1159-1168.
Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331 to 420 days) of baseline. Baseline plasma FGF23 was not associated with prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its co-receptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.
doi:10.1038/ki.2013.3
PMCID: PMC3672330  PMID: 23389416
phosphate; fibroblast growth factor 23; vascular calcification; vascular smooth muscle; chronic kidney disease
5.  Recruitment of Hispanics into an Observational Study of Chronic Kidney Disease:The Hispanic Chronic Renal Insufficiency Cohort Study Experience 
Contemporary clinical trials  2012;33(6):1238-1244.
Despite the large burden of chronic kidney disease (CKD) in Hispanics, this population has been underrepresented in research studies. We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study, which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospective observational cohort study. Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago, academic medical centers, and private nephrology practices. Methods of publicizing the study included church meetings, local Hispanic print media, Spanish television and radio stations, and local health fairs. From October 2005 to July 2008, we recruited 327 Hispanics aged 21–74 years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate (eGFR). Of 716 individuals completing a screening visit, 49% did not meet eGFR inclusion criteria and 46% completed a baseline visit. The mean age at enrollment was 57.1 and 67.1% of participants were male. Approximately 75% of enrolled individuals were Mexican American, 15% Puerto Rican, and 10% had other Latin American ancestry. Eighty two percent of participants were Spanish-speakers. Community-based and academic primary care clinics yielded the highest percentage of participants screened (45.9% and 22.4%) and enrolled (38.2% and 24.5%). However, academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened (61.9% to 71.4%). A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD.
doi:10.1016/j.cct.2012.07.012
PMCID: PMC3594841  PMID: 22841929
6.  Carotid Plaque, Carotid Intima-Media Thickness, and Coronary Calcification Equally Discriminate Prevalent Cardiovascular Disease in Kidney Disease 
American journal of nephrology  2012;36(4):342-347.
Background
Despite the significant morbidity and mortality attributable to cardiovascular disease (CVD), risk stratification remains an important challenge in the chronic kidney disease(CKD) population. We examined the discriminative ability of non-invasive measures of atherosclerosis, including carotid intima-media thickness(cIMT), carotid plaque, coronary artery calcification(CAC) and ascending and descending thoracic aorta calcification(TCAC), and Framingham Risk Score (FRS) to predict self-reported prevalent CVD.
Methods and Results
Participants were enrolled in the cIMT ancillary study of the Chronic Renal Insufficiency Cohort(CRIC) Study and also had all of the above measures within an 18 month period. CVD was present in 21% of study participants. C-statistics were used to ascertain the discriminatory power of each measure of atherosclerosis. The study population (n=220) was 64% male; 51% black and 45% white. The proportion of individuals with estimated glomerular filtration rate ≥60, 45–59, 30–44, and <30ml/min/1.73m2 was 21%, 41%, 28%, and 11%, respectively. In multivariable analyses adjusting for demographic factors, we failed to find a difference between CAC, carotid plaque, and cIMT as predictors of self-reported prevalent CVD (c-statistic 0.70, 95% confidence interval [CI]: 0.62–0.78; c-statistic 0.68, 95% CI: 0.60–0.75, and c-statistic 0.64, CI: 0.56–0.72, respectively). CAC was statistically better than FRS. FRS was the weakest discriminator of self-reported prevalent CVD (c-statistic 0.58).
Conclusions
There was a significant burden of atherosclerosis among individuals with CKD, ascertained by several different imaging modalities. We were unable to find a difference in the ability of CAC, carotid plaque, and cIMT to predict self-reported prevalent CVD.
doi:10.1159/000342794
PMCID: PMC3538165  PMID: 23107930
carotid intima media thickness; coronary artery calcification; kidney; plaque
7.  Mean platelet volume and prevalence of peripheral artery disease, the National Health and Nutrition Examination Survey, 1999–2004 
Atherosclerosis  2010;213(2):586-591.
Objectives
We sought to determine whether mean platelet volume (MPV) is associated with the prevalence of peripheral artery disease (PAD).
Background
Platelets play a pivotal role in the pathogenesis of atherosclerosis and PAD. MPV, a measure of platelet size available in every blood count, is increasingly recognized as an important marker of platelet activity.
Methods
We analyzed data from 6354 participants aged 40 years and older from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. PAD was defined as an ankle brachial index ≤0.90 in either leg. Odds ratios and 95% confidence intervals were estimated by logistic regression.
Results
The prevalence of PAD in the cohort was 5.7%. MPV was significantly associated with PAD prevalence (tertile 1 – 4.4%, tertile 2 – 6.1%, tertile 3 – 7.0%, P for trend = 0.003). After adjustment for age, sex, and race, the odds ratio of PAD comparing the highest tertile to the lowest tertile was 1.57 (95% confidence interval 1.15–2.13). After further adjustment for smoking status, hypertension, hypercholesterolemia, diabetes, glomerular filtration rate, body mass index, and platelet count the corresponding odds ratio was 1.58 (95% confidence interval 1.14–2.19). The addition of triglycerides, hemoglobin A1c, and C-reactive protein did not affect the results. The significant association between MPV and PAD was unchanged when MPV was used as a continuous variable.
Conclusions
Mean platelet volume is independently associated with PAD. These findings support the hypothesis that platelet size is an independent predictor of increased risk for PAD.
doi:10.1016/j.atherosclerosis.2010.09.010
PMCID: PMC3739454  PMID: 20940069
Mean platelet volume; Platelets; Peripheral artery disease; Epidemiology
8.  Mortality Predictive Indexes for the Community-Dwelling Elderly US Population 
ABSTRACT
Background
Few predictive indexes for long-term mortality have been developed for community-dwelling elderly populations. Parsimonious predictive indexes are important decision-making tools for clinicians, policy makers, and epidemiologists.
Objective
To develop 1-, 5-, and 10-year mortality predictive indexes for nationally representative community-dwelling elderly people.
Design
Cohort study.
Setting
The Second Longitudinal Study of Aging (LSOA II).
Participants
Nationally representative civilian community-dwelling persons at least 70 years old. We randomly selected 60% of the sample for prediction development and used the remaining 40% for validation.
Main Measures
Sociodemographics, impairments, and medical diagnoses were collected from the LSOA II baseline interviews. Instrumental activities of daily living (IADLs) stages were derived to measure functional status. All-cause mortality was obtained from the LSOA II Linked Mortality Public-use File.
Results
The analyses included 7,373 sample persons with complete data, among which mortality rates were 3.7%, 23.3%, and 49.8% for 1, 5, and 10 years, respectively. Four, eight, and ten predictors were identified for 1-, 5-, and 10-year mortality, respectively, in multiple logistic regression models to create three predictive indexes. Age, sex, coronary artery disease, and IADL stages were the most essential predictors for all three indexes. C-statistics of the three indexes were 0.72, 0.74, and 0.75 in the development cohort and 0.72, 0.72, and 0.74 in the validation cohort for 1-, 5-, and 10-year mortality, respectively. Five risk groups were defined based on the scores.
Conclusions
The 1-, 5-, and 10-year mortality indexes include parsimonious predictor sets maximizing ease of mortality prediction in community settings. Thus, they may provide valuable information for prognosis of elderly patients and guide the comparison of alternative interventions. Including IADL stage as a predictor yields simplified mortality prediction when detailed disease information is not available.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2027-3) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-012-2027-3
PMCID: PMC3403135  PMID: 22422075
mortality; prediction; score system; community; instrumental activities of daily living
9.  Estimating GFR Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study 
Background
Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies.
Study Design
Cross-sectional study of 1,433 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study (i.e., the GFR subcohort) to derive an internal GFR estimating equation using a split sample approach.
Setting & Participants
Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black.
Index Test
CRIC GFR estimating equation
Reference Test or Outcome
Urinary 125I-iothalamate clearance testing (measured GFR)
Other Measurements
Laboratory measures including serum creatinine and cystatin C, and anthropometrics
Results
In the validation dataset, the model that included serum creatinine, serum cystatin C, age, gender, and race was the most parsimonious and similarly predictive of mGFR compared to a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, the root mean square errors for the separate model were 0.207 vs. 0.202, respectively. The performance of the CRIC GFR estimating equation was most accurate among the subgroups of younger participants, men, non-blacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m2, those with higher 24-hour urine creatinine excretion, those with lower levels of high-sensitivity C-reactive protein, and those with higher mGFR.
Limitations
Urinary clearance of 125I-iothalamate is an imperfect measure of true GFR; cystatin C is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors.
Conclusions
The CRIC GFR estimating equation predicts measured GFR accurately in the CRIC cohort using serum creatinine and cystatin C, age, gender, and race. Its performance was best among younger and healthier participants.
doi:10.1053/j.ajkd.2012.04.012
PMCID: PMC3565578  PMID: 22658574
glomerular filtration rate (GFR); kidney function; GFR estimation
10.  Retinopathy and Chronic Kidney Disease in the Chronic Renal Insufficiency Cohort Study (CRIC) 
Archives of ophthalmology  2012;130(9):1136-1144.
Objectives
Retinal vascular and anatomic abnormalities caused by diabetes, hypertension, and other conditions can be observed directly in the ocular fundus and may reflect severity of chronic renal insufficiency. The purpose of this study was to investigate the association between retinopathy and chronic kidney disease (CKD).
Methods
In this observational, cross-sectional study, 2605 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, a multi-center study of CKD, were offered participation. Non-mydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects.
Photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and non-traditional risk factors for decreased kidney function were obtained from the CRIC study.
Results
Greater severity of retinopathy was associated with lower estimated glomerular filtration rate (eGFR) after adjustment for traditional and non-traditional risk factors. Presence of vascular abnormalities usually associated with hypertension was also associated with lower eGFR. We found no strong direct relationship between eGFR and average arteriolar or venular calibers.
Conclusions
Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and non-traditional risk factors for CKD, suggesting that retinovascular pathology reflects renal disease.
doi:10.1001/archophthalmol.2012.1800
PMCID: PMC3719171  PMID: 22965589
Retinopathy; Retinal Vascular Diameter; Chronic Kidney Disease
11.  Factors Associated With Home Discharge After Rehabilitation Among Male Veterans With Lower Extremity Amputation 
Objective
To determine the patient-, treatment-, and facility-level factors that are associated with home discharge among male veterans with lower extremity amputation who received inpatient rehabilitation after surgery.
Design
A retrospective observational study.
Setting
Veterans Affairs Medical Centers.
Participants
This study included 1480 male veterans.
Methods
Generalized estimating equation models were used to model the likelihood of home discharge to account for within-facility clustering. We reported odds ratios (ORs) and 95% confidence intervals (95% CIs).
Main Outcome Measurement
Discharged to home.
Results
There were a total of 1163 (78.6%) veterans who were discharged home after the surgical hospitalization, compared with other locations. Patients who were married were more likely to be discharged home compared with patients who were not married (OR = 1.51, 95% CI = 1.14–1.99, P < .01). Compared with being transferred from another hospital or extended care, patients who were admitted from home were far more likely to be discharged home (OR = 8.43, 95% CI = 5.48–12.96, P < .0001). Patients with evidence of local significant infection were less likely to be discharged home (OR = 0.57, 95% CI = 0.39–0.83, P < .01), as were patients with evidence of congestive heart failure (OR = 0.62, 95% CI = 0.45–0.85, P < .01) or depression (OR = 0.63, 95% CI = 0.40–0.98, P = .04). Veterans with greater discharge motor Functional Independence Measure scores were more likely to be discharged home (OR = 1.23, 95% CI = 1.16–1.31 per 10-point increase in discharge Functional Independence Measure motor score, P < .0001). Conversely, patients undergoing procedures for ongoing active cardiac pathology were less likely to be discharged home (OR = 0.55, 95% CI = 0.37–0.81, P < .01).
Conclusions
This study showed a strong association between the sociological factors of marital status and living location before hospitalization and home discharge. The significance of discharge functional status highlights the importance of addressing the expected care burden once patients are discharged home.
doi:10.1016/j.pmrj.2012.09.578
PMCID: PMC3718007  PMID: 23159239
12.  Association Between Retinopathy and Cardiovascular Disease in Patients with Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC] Study) 
The American Journal of Cardiology  2012;110(2):246-253.
Patients with chronic kidney disease (CKD) experience co-morbid illneses including cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between retinopathy and self reported CVD in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this observational, ancillary investigation, 2605 CRIC participants were invited to participate in this study, and non-mydriatic fundus photographs in both eyes were obtained in 1936 subjects. Photographs were reviewed in a masked fashion at a central photograph reading center. Presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter caliber were assessed using standard protocols by trained graders masked to information about study participants. History of self-reported cardiovascular disease was obtained using a medical history questionnaire. Kidney function measurements, traditional and non-traditional risk factors for CVD were obtained from the CRIC study. Greater severity of retinopathy was associated with higher prevalence of any cardiovascular disease and this association persisted after adjustment for traditional risk factors for CVD. Presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relationship between CVD prevalence and mean venular caliber. In conclusion, presence of retinopathy was associated with CVD, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. This would make assessment of retinal morphology a valuable tool in chronic kidney disease studies of CVD outcomes.
doi:10.1016/j.amjcard.2012.03.014
PMCID: PMC3383900  PMID: 22516527
Retinopathy; chronic kidney disease; cardiovascular disease
13.  Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies 
Background
Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.
Study Design
Cross-sectional analysis
Settings and Participants
Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008.
Measurement
Depressive symptoms measured by Beck Depression Inventory (BDI)
Predictors
Demographic and clinical factors
Outcomes
Elevated depressive symptoms (BDI >= 11) and antidepressant medication use
Results
Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each).
Limitations
Absence of clinical diagnosis of depression and use of non-pharmacologic treatments
Conclusions
Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. African Americans, Hispanics, and individuals with more advanced CKD had higher odds of elevated depressive symptoms and lower odds of antidepressant medication use.
doi:10.1053/j.ajkd.2011.12.033
PMCID: PMC3378778  PMID: 22497791
14.  Risk Factors for Peripheral Arterial Disease among Patients with Chronic Kidney Disease 
The American journal of cardiology  2012;110(1):136-141.
Patients with chronic kidney disease (CKD) have an increased risk of developing peripheral arterial disease (PAD). We examined the cross-sectional association between novel risk factors and prevalent PAD among patients with CKD. A total of 3,758 patients with an estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2 who participated in the chronic renal insufficiency cohort (CRIC) study were included in the current analysis. PAD was defined as an ankle-brachial index <0.9 or a history of arm or leg revascularization. After adjustment for age, sex, race, cigarette smoking, physical activity, history of hypertension and diabetes, pulse pressure, high-density lipoprotein cholesterol, eGFR, and CRIC clinical sites, several novel risk factors were significantly associated with PAD. For example, odds ratios (95% confidence intervals) for a one standard deviation higher level of risk factors were 1.18 (1.08–1.29) for log-transformed high sensitivity-C reactive protein, 1.18 (1.08–1.29) for white blood cell count, 1.15 (1.05–1.25) for fibrinogen, 1.13 (1.03–1.24) for uric acid, 1.14 (1.02–1.26) for hemoglobin A1c, 1.11 (1.00–1.23) for log-transformed homeostasis model assessment-insulin resistance, and 1.35 (1.18–1.55) for cystatin C. In conclusion, these data indicate that inflammation, prothrombotic state, oxidative stress, insulin resistance, and cystatin C were associated with an increased prevalence of PAD in patients with CKD. Further studies are warranted to examine the causal effect of these risk factors on PAD in CKD patients.
doi:10.1016/j.amjcard.2012.02.061
PMCID: PMC3586781  PMID: 22465315
peripheral arterial disease; novel risk factors; chronic kidney disease
15.  Validation of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36™) US Spanish and English Versions in a Cohort of Hispanics with Chronic Kidney Disease 
Ethnicity & disease  2013;23(2):202-209.
Objective
Evaluate the reliability and validity of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36™) in Hispanics with mild-to-moderate chronic kidney disease (CKD).
Design
Cross-sectional
Setting
Chronic Renal Insufficiency Cohort Study
Participants
420 Hispanic (150 English- and 270 Spanish-speakers), and 409 non-Hispanic White individuals, matched by age (mean 57 years), sex (60% male), kidney function (mean estimated glomerular filtration rate 36ml/min/1.73m2), and diabetes (70%).
Methods
To measure construct validity, we selected instruments, comorbidities, and laboratory tests related to at least one KDQOL-36™ subscale. Reliability was determined by calculating Cronbach’s alpha.
Results
Reliability of each KDQOL-36™ subscale [SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS), Symptoms/Problems, Burden of Kidney Disease and Effects of Kidney Disease] was very good (Cronbach’s alpha >0.8). Construct validity was supported by expected negative correlation between MCS scores and the Beck Depression Inventory in all three subgroups (r= −0.56 to −0.61, P<.0001). There was inverse correlation between the Symptoms/Problems subscale and the Patient Symptom Form (r= −0.70 to −0.77, P<.0001). We also found significant, positive correlation between the PCS score and a physical activity survey (r= +0.29 to +0.38, P≤.003); and between the PCS and MCS scores and the Kansas City Questionnaire (r= +0.31 to +0.64, P<.0001). Reliability and validity were similar across all racial/ethnic groups analyzed separately.
Conclusion
Our findings support the use of the KDQOL-36™ as a measure of HRQOL in this cohort of US Hispanics with CKD.
PMCID: PMC3651651  PMID: 23530302
Validation; Quality of Life; Hispanics
16.  The Relationship Between Diabetes, Metabolic Syndrome, and Platelet Activity as Measured by Mean Platelet Volume 
Diabetes Care  2012;35(5):1074-1078.
OBJECTIVE
The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control.
RESEARCH DESIGN AND METHODS
This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression.
RESULTS
MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control.
CONCLUSIONS
Mean platelet volume is strongly and independently associated with the presence and severity of diabetes.
doi:10.2337/dc11-1724
PMCID: PMC3329806  PMID: 22410814
17.  Revisiting risks associated with mortality following initial transtibial or transfemoral amputation 
This study’s objective was to determine how treatment-, environmental-, and facility-level characteristics contribute to postdischarge mortality prediction. The study included 4,153 Veterans who underwent lower-limb amputation in Department of Veterans Affairs facilities during fiscal years 2003 and 2004. Veterans were followed 1 yr postamputation. A Cox regression identified characteristics associated with mortality risk after hospital discharge following amputation. Older age, higher amputation level, and more comorbidities increased mortality likelihood. Patients who had inpatient procedures for pulmonary and renal problems had higher hazards of postdischarge death than those who did not (hazard ratio [HR] = 2.10, 95% confidence interval [CI] = 1.16–3.77, and HR = 2.22, 95% CI = 1.80–2.74, respectively). Patients who had central nervous system procedures had higher hazards of death early postdischarge (HR = 2.23, 95% CI = 1.60–3.11) at 0 d, but this association became insignificant by 180 d. Patients in a surgical intensive care unit (ICU), medical ICU, or medical bed section at the time of discharge were more likely to die than patients on a surgical bed section. Patients hospitalized in the Midwest were less likely to die early after discharge than patients in the Mountain Pacific region, but this regional effect became insignificant by 90 d. Adding treatment-, environmental-, and facility-level characteristics contributed additional information to a mortality risk model.
PMCID: PMC3628826  PMID: 23516052
administrative data; amputation; comorbidity; elderly; integrated; lower limb; mortality; outcome assessment; rehabilitation; Veteran
18.  All-Cause 1-, 5-, and 10-Year Mortality Among Elderly People According to Activities of Daily Living Stage 
Background
Limitation in the activities of daily living (ADLs) is strongly prognostic for mortality. Current ADL assessments based on numbers of limitations (counts) obscure the particular activities limited, thus lacking clinical interpretability.
Objectives
To examine the independent association of 5 stages of ADL with mortality after accounting for known diagnostic and sociodemographic risk factors.
Design
For five stages (ADL 0 to IV), describing both the severity and pattern of ADLs limited, we estimated unadjusted life expectancies and adjusted associations with mortality using a Cox proportional hazards regression model.
Setting
Community
Participants
Included were 9,447 persons 70 years of age and older from the second Longitudinal Study of Aging.
Measurements
1-, 5-, and 10-year survival and time to death.
Results
For those with no ADL limitations, the median life expectancy was 10.6 years compared to 6.5, 5.1, 3.8, and 1.6 years for those at ADL I, II, III, and IV, respectively. The sociodemographic and diagnostic-adjusted hazard of death at 1 year was 5-fold greater at stage IV compared to stage 0 (hazard ratio=5.6; 95% confidence interval, 3.8–8.3). The associations of ADL stage with mortality declined over time, but remained statistically significant at 5 and 10 years.
Conclusion
ADL stage continued to explain mortality risk after adjusting for known risk factors including advanced age, stroke, and cancer. ADL stages might aid clinical care planning and policy as a powerful prognostic indicator particularly of short-term mortality, improving on current ADL measures by profiling activity limitations of relevance to determining community support needs.
doi:10.1111/j.1532-5415.2011.03867.x
PMCID: PMC3302958  PMID: 22352414
Activities of Daily Living; Staging; Mortality; Risk factors
19.  CKD in Hispanics: Baseline Characteristics From the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC Studies 
Background
Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants.
Study Design
Cross-sectional analysis
Setting and Participants
Participants were aged 21–74 years with CKD using age-based glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois from 2005–2008 while CRIC included Hispanics and non-Hispanics recruited at seven clinical centers from 2003–2007.
Factor
Race/ethnicity
Outcomes
Blood pressure, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, CKD-associated complications
Measurements
Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols
Results
Among H-CRIC/ CRIC participants, 497 were Hispanic, 1650 non-Hispanic Black, and 1638 non-Hispanic White. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (p<0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic Blacks (51%) and Whites (40%) (p<0.01). Blood pressure > 130/80 mmHg was more common in Hispanics (62%) compared with Blacks (57%) and Whites (35%) (p<0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (p<0.05), even after stratifying by entry eGFR. Hispanics had the lowest receipt of ACE inhibitor/ARB among high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure > 130/80 mmHg. Mean eGFR (ml/min/m2) was lower in Hispanics (39.6) than in Blacks (43.7) and Whites (46.2), while median proteinuria was higher in Hispanics (0.72 g/d) than in Blacks (0.24 g/d) and Whites (0.12 g/d) (p<0.01).
Limitations
Generalizability; observed associations limited by residual bias and confounding
Conclusions
Hispanics with CKD in CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts.
doi:10.1053/j.ajkd.2011.05.010
PMCID: PMC3577064  PMID: 21705121
chronic kidney disease; Hispanics; epidemiology
20.  Patient-, Treatment-, and Facility-Level Structural Characteristics Associated With the Receipt of Preoperative Lower Extremity Amputation Rehabilitation 
Objectives
To determine patient, treatment, or facility characteristics that influence decisions to initiate a rehabilitation assessment before transtibial or transfemoral amputation within the Veterans Affairs (VA) health care system.
Design
Retrospective database study.
Setting
VA medical centers.
Participants
A total of 4226 veterans with lower extremity amputations discharged from a VA medical center between October 1, 2002, and September 30, 2004.
Outcome
Evidence of a preoperative rehabilitation assessment after the index surgical stay admission but before the surgical date.
Results
Evidence was found that 343 of 4226 veterans (8.12%) with lower extremity amputations received preoperative rehabilitation assessments. Veterans receiving preoperative rehabilitation were more likely to be older, admitted from home, or transferred from another hospital. Patients who underwent surgical amputation at smaller-sized hospitals or in the South Central or Mountain Pacific regions were more likely to receive preoperative rehabilitation compared with patients in mid-sized hospitals or in the Northeast, Southeast, or Midwest regions. Patients with evidence of paralysis, patients treated in facilities with programs accredited by the Commission on Accreditation of Rehabilitation Facilities (P < .01), and patients in the second data wave were less likely to receive preoperative rehabilitation. After accounting for patient-, treatment-, and facility-level structural characteristics, we found that older patients were more likely to receive preoperative rehabilitation services (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.02). Patients with a contributing amputation etiology of a previous amputation complication were more likely to receive preoperative consultation rehabilitation services (OR 1.50, 95% CI 1.02–2.19) compared with patients who did not have this etiology. Compared with patients treated in the Southeast region of the United States, those treated in the South Central region (OR 2.52, 95% CI 1.82–3.48) or Mountain Pacific region (OR 1.62, 95% CI 1.11–2.37) were more likely to receive preoperative consultation rehabilitation services. Patients with evidence of paralysis were less likely to receive preoperative rehabilitative services compared with patients who did not have this condition (OR 0.29, 95% CI 0.09–0.93), and patients treated in mid-sized hospitals also were less likely to receive preoperative rehabilitative services compared with patients treated in smaller-sized facilities (OR 0.38, 95% CI 0.27–0.53). Veterans in the second data year were less likely to receive services compared with patients in the first year (OR 0.74, 95% CI 0.58–0.94).
Conclusions
Rehabilitation assessment before lower extremity amputation surgery is a rare occurrence in the VA health care system. Practice patterns appear to be driven by location and not by patient characteristics.
doi:10.1016/j.pmrj.2012.06.009
PMCID: PMC3570975  PMID: 22939239
21.  Obesity, diabetes, and exercise associated with sleep-related complaints in the American population 
Aim
Previous studies have demonstrated relationships between sleep and both obesity and diabetes. Additionally, exercise may improve sleep and daytime function, in addition to weight and metabolic function. The present study extends these findings by examining how general sleep-related complaints are associated with body mass index (BMI), diabetes diagnosis, and exercise in a large, nationally representative sample.
Subject and methods
Participants were respondents to the Behavioral Risk Factor Surveillance System (BRFSS). Sleep complaint (SC) was measured with “Over the last 2 weeks, how many days have you had trouble falling asleep or staying asleep or sleeping too much?” Daytime complaint (DC) was measured with “Over the last 2 weeks, how many days have you felt tired or had little energy?” Responses were dichotomized, with ≥6 days indicating complaint. Covariates included age, race/ethnicity, income, and education.
Results
Being overweight was associated with DC in women only. Obesity was significantly associated with SC and DC in women, and DC in men. Diabetes was associated with SC and DC in both genders. Any exercise in the past 30 days did not attenuate any BMI or diabetes relationships, but was independently associated with a decrease in SC and DC in both men and women.
Conclusion
These results suggest that for both men and women diabetes is a significant predictor of sleep and daytime complaints, and there is a relationship between obesity and sleep and complaints for women to a greater extent than men. Finally, exercise was associated with much fewer sleep and daytime complaints in both genders.
doi:10.1007/s10389-011-0398-2
PMCID: PMC3392306  PMID: 22791935
Sleep; Sleep disturbance; Obesity; Diabetes; Exercise
22.  Home Accessibility, Living Circumstances, Stage of Activity Limitation, and Nursing Home Use 
Objective
To explore the influence of physical home and social environments and disability patterns on nursing home (NH) use.
Design
Longitudinal cohort study. Self- or proxy-reported perception of home environmental barriers accessibility, 5 stages expressing the severity and pattern of activities of daily living (ADLs) limitations, and other characteristics at baseline were applied to predict NH use within 2 years or prior to death through logistic regression.
Setting
General community.
Participants
Population-based, community-dwelling individuals (N=7836; ≥70y) from the Second Longitudinal Study of Aging interviewed in 1994 with 2-year follow-up that was prospectively collected.
Interventions
Not applicable.
Main Outcome Measure
NH use within 2 years.
Results
Perceptions of home environmental barriers and living alone were both associated with approximately 40% increased odds of NH use after adjustment for other factors. Compared with those with no limitations at ADL stage 0, the odds of NH use peaked for those with severe limitations at ADL stage III (odds ratio [OR]=3.12; 95% confidence interval [CI], 2.20 – 4.41), then declined sharply for those with total limitations at ADL stage IV (OR=.96; 95% CI, .33–2.81). Sensitivity analyses for missing NH use showed similar results.
Conclusions
Accessibility of home environment, living circumstance, and ADL stage represent potentially modifiable targets for rehabilitation interventions for decreasing NH use in the aging U.S. population.
doi:10.1016/j.apmr.2012.03.027
PMCID: PMC3461316  PMID: 22484216
Activities of daily living; Nursing homes; Rehabilitation
23.  Factors influencing receipt of outpatient rehabilitation services among veterans following lower extremity amputation 
Objective
To determine patient-, treatment-, and facility-level characteristics associated with receiving outpatient rehabilitation services following lower extremity amputation within Veterans Affairs (VA) system.
Design
A Cox proportional hazards model was used to determine the adjusted hazard ratio and 95% confidence interval of veterans to receive outpatient services.
Setting
All VA Medical Centers.
Participants
4,165 veterans with lower-extremity amputation discharged from VAMCs between October 1, 2002, and September 20, 2004.
Intervention
Not applicable.
Main Outcome Measures
Receipt of outpatient rehabilitation services up to one year post-discharge.
Results
Sixty-five percent of veterans with lower extremity amputation received outpatient services. Older veterans, patients admitted for surgical amputation from extended care rather than transferred from another hospital, and those with trans-femoral and/or bilateral rather than unilateral trans-tibial amputations were less likely to receive outpatient services. Those with serious comorbidities and those who had procedures for acute central nervous disorders, active cardiac pathology, serious nutritional compromise, and severe renal disease during the surgical hospitalization less often initiated outpatient care. Patients who received inpatient consultative rehabilitation compared to inpatient specialized rehabilitation; and who were treated in the Northeast compared to the Southeast region less often initiated outpatient care. Finally those discharged to home or other locations rather than extended care had an initial increased likelihood of receiving outpatient service, but by 180 days post-discharge those discharged to extended care were more likely to initiate outpatient services.
Conclusion
Both clinical characteristics and types of rehabilitation services received appear to influence receipt of outpatient rehabilitation services. Geographic location also impacted receipt of outpatient rehabilitation, suggesting that care patterns are not standardized across the nation.
doi:10.1016/j.apmr.2011.03.029
PMCID: PMC3188813  PMID: 21878217
lower extremity amputation; outpatient rehabilitation; veterans
24.  Do Elderly People at More Severe Activity of Daily Living Limitation Stages Fall More? 
Henry-Sánchez JT, Kurichi JE, Xie D, Pan Q, Stineman MG: Do elderly people at more severe activity of daily living limitation stages fall more? Am J Phys Med Rehabil 2012;91:601–610.
Objective
The aim of this study was to explore how activity of daily living (ADL) stages and the perception of unmet needs for home accessibility features associate with a history of falling.
Design
Participants were from a nationally representative sample from the Second Longitudinal Survey of Aging conducted in 1994. The sample included 9250 community-dwelling persons 70 yrs or older. The associations of ADL stage and perception of unmet needs for home accessibility features with a history of falling within the past year (none, once, or multiple times) were explored after accounting for sociodemographic characteristics and comorbidities using a multinomial logistic regression model.
Results
The adjusted relative risk of falling more than once peaked at 4.30 (95% confidence interval, 3.29–5.61) for persons with severe limitation (ADL-III) compared those with no limitation (ADL-0) then declined for those at complete limitation (ADL-IV). The adjusted relative risks of falling once and multiple times were 1.42 (95% confidence interval, 1.07–1.87) and 1.85 (95% confidence interval, 1.44–2.36), respectively, for those lacking home accessibility features.
Conclusions
Risk of falling appeared greatest for those whose homes lacked accessibility features and peaked at intermediate ADL limitation stages, presumably at a point when people have significant disabilities but sufficient function to remain partially active.
doi:10.1097/PHM.0b013e31825596af
PMCID: PMC3422022  PMID: 22561383
Accidental Falls; Aged; Risk Assessment; Activities of Daily Living
25.  Metabolic Syndrome, Components, and Cardiovascular Disease Prevalence in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study 
American Journal of Nephrology  2011;33(6):477-484.
Background/Aims
Metabolic syndrome may increase the risk for incident cardiovascular disease (CVD) and all-cause mortality in the general population. It is unclear whether, and to what degree, metabolic syndrome is associated with CVD in chronic kidney disease (CKD). We determined metabolic syndrome prevalence among individuals with a broad spectrum of kidney dysfunction, examining the role of the individual elements of metabolic syndrome and their relationship to prevalent CVD.
Methods
We evaluated four models to compare metabolic syndrome or its components to predict prevalent CVD using prevalence ratios in the Chronic Renal Insufficiency Cohort (CRIC) Study.
Results
Among 3,939 CKD participants, the prevalence of metabolic syndrome was 65% and there was a significant association with prevalent CVD. Metabolic syndrome was more common in diabetics (87.5%) compared with non-diabetics (44.3%). Hypertension was the most prevalent component, and increased triglycerides the least prevalent. Using the bayesian information criterion, we found that the factors defining metabolic syndrome, considered as a single interval-scaled variable, was the best of four models of metabolic syndrome, both for CKD participants overall and for diabetics and non-diabetics separately.
Conclusion
The predictive value of this model for future CVD outcomes will subsequently be validated in longitudinal analyses.
doi:10.1159/000327618
PMCID: PMC3095834  PMID: 21525746
Cardiovascular disease; Chronic kidney disease; Chronic Renal Insufficiency Cohort (CRIC) Study; Metabolic syndrome

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