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2.  Association of Cardiac Troponin T With Left Ventricular Structure and Function in CKD 
Background
Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without heart failure.
Study Design
Cross-sectional.
Setting & Participants
Chronic Renal Insufficiency Cohort (CRIC; N= 3,243)
Predictor
The primary predictor was cTnT. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein, and estimated glomerular filtration rate using cystatin C.
Outcomes
Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function.
Measurements
Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT with each echocardiographic outcome.
Results
cTnT was detectable in 2,735 (84%) persons; the median was 13.3 (IQR, 7.7–23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9 – 738.7 pg/mL) was associated with approximately two times as likely to experience LV hypertrophy (OR, 2.43; 95% CI, 1.44–4.09) in the fully adjusted model. cTnT had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.1–1.7] per 1-log unit; p<0.01). There was no significant independent association between cTnT and LV diastolic dysfunction. When evaluated as a screening test, cTnT functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both) with weaker areas under the curve for the other outcomes.
Limitations
The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study.
Conclusions
In this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in CKD are predominantly an indicator of pathological LV hypertrophy.
doi:10.1053/j.ajkd.2012.11.034
PMCID: PMC3627820  PMID: 23291148
Troponin T; left ventricular structure; chronic kidney disease
3.  Depressive symptoms and chronic kidney disease: results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 
International urology and nephrology  2010;42(4):1063-1068.
Background and objective
Depression is common in individuals with end-stage renal disease. However, its relationship with earlier stages of chronic kidney disease (CKD) is less well known. In this study, we examined the association between depressive symptoms and CKD.
Methods
Cross-sectional analysis of the prevalence and correlates of depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9) among adult participants with CKD in the National Health and Nutrition Examination Survey 2005–2006. CKD was defined according to estimated glomerular filtration rate by Modification of Diet in Renal Disease Study equation of <60 ml/min/1.73 m2 or the presence of microalbuminuria (≥30 mg/g creatinine), using the Kidney Disease Outcomes Quality Initiative classification. A PHQ-9 score ≥ 10 was considered to be indicative of depressive symptoms.
Results
Among 3653 subjects in our study sample, 683 (15.2%) met laboratory criteria for CKD. The prevalence of depressive symptoms was 7% (95% confidence interval [CI] 3.2–10.8%) in subjects with CKD and 6% (95% CI 4.6–7.4%) in subjects without CKD (P = 0.6). In regression analysis, the presence of CKD was not significantly associated with depressive symptoms (adjusted odds ratio = 0.96 [95% CI 0.51, 1.78], P = 0.9).
Conclusions
We found no difference in the prevalence of depressive symptoms among individuals with or without CKD.
doi:10.1007/s11255-010-9833-5
PMCID: PMC3951180  PMID: 20949318
Chronic kidney disease; Depression; National Health and Nutrition Examination Survey; Prevalence
4.  Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study 
Clinical nephrology  2014;81(1):30-37.
Background
Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited.
Methods
We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 – 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score ≤ 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors.
Results
The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m2); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p ≤ 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 – 2.03) and lower eGFR (β − 2.47, p = 0.03).
Conclusion
In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD.
doi:10.5414/CN108062
PMCID: PMC3951206  PMID: 24219913
chronic kidney disease; health literacy
5.  Illicit Drug Use, Hypertension, and Chronic Kidney Disease in the U.S. Adult Population 
Illicit drug use has been associated with chronic kidney disease (CKD) in select populations but it is unknown if the same association exists in the general population. Using data from the National Health and Nutrition Examination Survey 2005-2008, we conducted a cross-sectional analysis of 5,861 adults who were questioned about illicit drug use including cocaine, methamphetamines, or heroin during their lifetime. The primary outcome was CKD as defined by an estimated glomerular filtration rate (eGFR) ≤60mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or by microalbuminuria. We also examined the association between illicit drug use and blood pressure (BP) ≥120/80, ≥130/85, and ≥140/90. Logistic regression was used to examine the association between illicit drug use and CKD and BP. Mean eGFR was similar between illicit drug users and non-users (100.7 vs. 101.4mL/min/1.73m2, p=0.4) as was albuminuria (5.7 vs. 6.0mg/g creatinine, p=0.5). Accordingly, illicit drug use was not significantly associated with CKD in logistic regression models (odds ratio [OR] 0.98, confidence interval [CI] 0.75-1.27) after adjusting for other important factors. However, illicit drug users had higher systolic (120 vs. 118mmHg, p=0.04) and diastolic BP (73 vs. 71mmHg, p=0.0003) compared to non-users. Also, cocaine use was independently associated with BP≥130/85 (OR 1.24, CI 1.00-1.54), especially when used more during a lifetime (6-49 times, OR 1.42, CI 1.06-1.91). In a representative sample of the U.S. population, illicit drug use was not associated with CKD but cocaine users were more likely to have elevated blood pressures.
doi:10.1016/j.trsl.2012.05.008
PMCID: PMC3461092  PMID: 22735028
6.  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
7.  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
8.  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
9.  Chronic kidney disease is associated with adverse outcomes among elderly patients taking clopidogrel after hospitalization for acute coronary syndrome 
BMC Nephrology  2013;14:107.
Background
Chronic kidney disease (CKD) is associated with worse outcomes among patients with acute coronary syndrome (ACS). Less is known about the impact of CKD on longitudinal outcomes among clopidogrel treated patients following ACS.
Methods
Using a retrospective cohort design, we identified patients hospitalized with ACS between 10/1/2005 and 1/10/10 at Department of Veterans Affairs (VA) facilities and who were discharged on clopidogrel. Using outpatient serum creatinine values, estimated glomerular filtration rate [eGFR (1.73 ml/min/m2)] was calculated using the CKD-EPI equation. The association between eGFR and mortality, hospitalization for acute myocardial infarction (AMI), and major bleeding were examined using Cox proportional hazards models.
Results
Among 7413 patients hospitalized with ACS and discharged taking clopidogrel, 34.5% had eGFR 30–60 and 11.6% had eGFR < 30. During 1-year follow-up after hospital discharge, 10% of the cohort died, 18% were hospitalized for AMI, and 4% had a major bleeding event. Compared to those with eGFR > =60, individuals with eGFR 30–60 (HR 1.45; 95% CI: 1.18-1.76) and < 30 (HR 2.48; 95% CI: 1.97-3.13) had a significantly higher risk of death. A progressive increased risk of AMI hospitalization was associated with declining eGFR: HR 1.20; 95% CI: 1.04-1.37 for eGFR 30–60 and HR 1.47; 95% CI: 1.22-1.78 for eGFR < 30. eGFR < 30 was independently associated with over a 2-fold increased risk in major bleeding (HR 2.09; 95% CI: 1.40-3.12) compared with eGFR > = 60.
Conclusion
Lower levels of kidney function were associated with higher rates of death, AMI hospitalization, and major bleeding among patients taking clopidogrel after hospitalization for ACS.
doi:10.1186/1471-2369-14-107
PMCID: PMC3668174  PMID: 23688069
Kidney disease; Myocardial infarction; Hospitalization; Bleeding
10.  5,6-EET Is Released upon Neuronal Activity and Induces Mechanical Pain Hypersensitivity via TRPA1 on Central Afferent Terminals 
The Journal of Neuroscience  2012;32(18):6364-6372.
Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient receptor potential (TRP) channel activation in nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, 5,6-EET levels increased in dorsal root ganglia (DRGs) and the dorsal spinal cord, and 5,6-EET is released from activated sensory neurons in vitro. 5,6-EET potently induced a calcium flux (100 nm) in cultured DRG neurons that was completely abolished when TRPA1 was deleted or inhibited. In spinal cord slices, 5,6-EET dose dependently enhanced the frequency, but not the amplitude, of spontaneous EPSCs (sEPSCs) in lamina II neurons that also responded to mustard oil (allyl isothiocyanate), indicating a presynaptic action. Furthermore, 5,6-EET-induced enhancement of sEPSC frequency was abolished in TRPA1-null mice, suggesting that 5,6-EET presynaptically facilitated spinal cord synaptic transmission by TRPA1. Finally, in vivo intrathecal injection of 5,6-EET caused mechanical allodynia in wild-type but not TRPA1-null mice. We conclude that 5,6-EET is synthesized on the acute activation of nociceptors and can produce mechanical hypersensitivity via TRPA1 at central afferent terminals in the spinal cord.
doi:10.1523/JNEUROSCI.5793-11.2012
PMCID: PMC3359875  PMID: 22553041
11.  Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease 
Kidney international  2011;80(6):670-678.
This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease.
doi:10.1038/ki.2011.153
PMCID: PMC3237701  PMID: 21633409
AASK (African American Study of Kidney Disease and Hypertension); cardiovascular events; chronic kidney disease; depression
12.  Quality of Life and Psychosocial Factors in African Americans with Hypertensive Chronic Kidney Disease 
Health-related quality of life (HRQOL) is poorly understood in patients with chronic kidney disease (CKD) prior to end-stage renal disease. The association between psychosocial measures and HRQOL has not been fully explored in CKD, especially in African Americans. We performed a cross-sectional analysis of HRQOL and its association with sociodemographic and psychosocial factors in African Americans with hypertensive CKD.
There were 639 participants in the African American Study of Kidney Disease and Hypertension Cohort Study. The Short Form-36 was used to measure HRQOL. The Diener Satisfaction with Life Scale measured life satisfaction, the Beck Depression Inventory-II assessed depression, the Coping Skills Inventory-Short Form measured coping, and the Interpersonal Support Evaluation List-16 was used to measure social support.
Mean participant age was 60 years at enrollment, and 61% were male. Forty-two percent reported a household income below $15,000/year. Higher levels of social support, coping skills, and life satisfaction were associated with higher HRQOL, while unemployment and depression were associated with lower HRQOL (p<0.05). There was a significant positive association between higher estimated glomerular filtration rate (eGFR) with the Physical Health Composite (PHC) score (p=0.004) but not the Mental Health Composite (MHC) score (p=0.24).
Unemployment was associated with lower HRQOL, and lower eGFR was associated with lower PHC. African Americans with hypertensive CKD with better social support and coping skills had higher HRQOL. This study demonstrates an association between CKD and low HRQOL and highlights the need for longitudinal studies to further examine this association.
doi:10.1016/j.trsl.2011.09.004
PMCID: PMC3240805  PMID: 22153804
13.  Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease 
Kidney international  2010;77(11):1010-1019.
Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50–60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups.
doi:10.1038/ki.2010.38
PMCID: PMC3114445  PMID: 20200503
AASK (African American Study of Kidney Disease and Hypertension); chronic kidney disease; clinical epidemiology; depression; quality of life
14.  The Antiphospholipid Syndrome 
Seminars in nephrology  2007;27(1):35-46.
Summary
The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hyper-coagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS.
doi:10.1016/j.semnephrol.2006.09.006
PMCID: PMC3440307  PMID: 17336687 CAMSID: cams2313
Antiphospholipid antibodies; antiphospholipid antibody syndrome; thrombosis; thromboembolism; venous thrombosis; anticardiolipin antibody; lupus coagulation inhibitor; beta-2 glycoprotein I; thrombotic microangiopathy
15.  Hepatitis C and the Risk of Kidney Disease and Mortality in Veterans With HIV 
Objectives
To examine the effect of hepatitis C virus (HCV) on the prevalence of chronic kidney disease (CKD) among veterans with HIV and to evaluate independent associations of HCV and CKD with mortality.
Methods
We studied a national cohort of HIV-infected patients receiving care through the Veterans Healthcare Administration from 1998 to 2004. CKD was defined as an estimated glomerular filtration rate [eGFR (mL/min/1.73 m2)] < 60. Poisson regression was used to assess relationships between CKD, HCV, and mortality.
Results
Among 23,155 HIV-infected veterans, 12% had CKD. Forty percent of the cohort was coinfected with HCV, and a higher proportion of coinfected subjects had CKD compared with monoinfected subjects (14% vs 11%, P < 0.001). During the median follow-up of 7.6 years, 37% of subjects died and a graduated increase in adjusted mortality rates occurred with lower levels of eGFR (P < 0.001). Adjusted mortality rates were consistently higher in HCV-coinfected subjects across all levels of eGFR (P < 0.001). HCV was independently associated with increased mortality (incidence rate ratio 1.23, 95% confidence interval 1.17–1.29).
Conclusions
CKD is prevalent in HIV-infected veterans and associated with substantially higher mortality. Compared with their monoinfected counterparts, veterans coinfected with HCV have significantly higher rates of CKD and mortality.
doi:10.1097/QAI.0b013e3181b980d4
PMCID: PMC3032564  PMID: 20104121
death; HIV; hepatitis C; kidney failure; veterans
16.  Progression of CKD in Hispanics: Potential Roles of Health Literacy, Acculturation, and Social Support 
Hispanics are the fastest growing minority group in the United States and, compared with non-Hispanic whites, have a higher incidence of end-stage renal disease (ESRD). Examining novel factors that may explain this disparity in progression of chronic kidney disease (CKD) in Hispanics is urgently needed. Interpersonal and patient-centered characteristics, including health literacy, acculturation, and social support have been shown to affect health outcomes in other chronic diseases. However, these characteristics have not been well studied in the context of CKD, particularly in relation to disease knowledge, attitudes, and behaviors. In this paper, we examine the potential roles of these factors upon CKD progression in Hispanics and propose targeted therapeutic interventions.
doi:10.1053/j.ajkd.2011.05.004
PMCID: PMC3144398  PMID: 21787982
Chronic kidney disease; Hispanics; health disparities; health literacy; acculturation; social support
17.  Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation 
Molecular Pain  2011;7:78.
Background
Cytochrome-P450 (CYP450) epoxygenases metabolise arachidonic acid (AA) into four different biologically active epoxyeicosatrienoic acid (EET) regioisomers. Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly hydrolysed by the enzyme soluble epoxide hydrolase (sEH). Here, we investigated the role of sEH in nociceptive processing during peripheral inflammation.
Results
In dorsal root ganglia (DRG), we found that sEH is expressed in medium and large diameter neurofilament 200-positive neurons. Isolated DRG-neurons from sEH-/- mice showed higher EET and lower DHET levels. Upon AA stimulation, the largest changes in EET levels occurred in culture media, indicating both that cell associated EET concentrations quickly reach saturation and EET-hydrolyzing activity mostly effects extracellular EET signaling. In vivo, DRGs from sEH-deficient mice exhibited elevated 8,9-, 11,12- and 14,15-EET-levels. Interestingly, EET levels did not increase at the site of zymosan-induced inflammation. Cellular imaging experiments revealed direct calcium flux responses to 8,9-EET in a subpopulation of nociceptors. In addition, 8,9-EET sensitized AITC-induced calcium increases in DRG neurons and AITC-induced calcitonin gene related peptide (CGRP) release from sciatic nerve axons, indicating that 8,9-EET sensitizes TRPA1-expressing neurons, which are known to contribute to mechanical hyperalgesia. Supporting this, sEH-/- mice showed increased nociceptive responses to mechanical stimulation during zymosan-induced inflammation and 8,9-EET injection reduced mechanical thresholds in naive mice.
Conclusion
Our results show that the sEH can regulate mechanical hyperalgesia during inflammation by inactivating 8,9-EET, which sensitizes TRPA1-expressing nociceptors. Therefore we suggest that influencing the CYP450 pathway, which is actually highly considered to treat cardiovascular diseases, may cause pain side effects.
doi:10.1186/1744-8069-7-78
PMCID: PMC3195722  PMID: 21970373
sEH; EET; CYP450; nociceptors; TRPA1; hyperalgesia
18.  Uncomplicated Acute Renal Failure and Post-Hospital Care: A Not So Uncomplicated Illness 
American Journal of Nephrology  2008;28(3):523-530.
Background
Although uncomplicated acute renal failure (ARF) is associated with significant hospital resource utilization, its health care requirements following hospital discharge are not well understood. The goal of this study was to characterize the post-hospital care requirements incurred by patients with uncomplicated ARF and to determine its important influencing factors.
Methods
We obtained hospital case mix data sets for a 2-year period (1999–2000) from the Massachusetts Division of Health Care Finance and Policy. Utilizing DRG and ICD-9-CM codes from 23 Massachusetts hospitals, we identified 2,128 adult patients whose primary reason for hospitalization was uncomplicated ARF. Post-hospital care was defined as the receipt of extended facility care or home health care following hospital discharge.
Results
Nearly 50% of patients hospitalized with uncomplicated ARF required some type of post-hospital care, of whom 27% underwent extended facility care while 22% received home health care. The post-hospital care requirements for uncomplicated ARF were similar to those for serious medical conditions (e.g. heart failure) and exceeded those of many common illnesses (e.g., bronchitis). Advancing age, worsening severity of illness, female gender, and emergency room admission were independently associated with receipt of post-hospital care (p < 0.05). A trend existed between less frequent post-hospital care requirements and hospitalization at academic medical centers compared with non-academic hospitals.
Conclusions
Uncomplicated ARF is frequently associated with prolonged care following hospitalization. As the health care utilization for ARF becomes better characterized, these post-hospital care resources should not be overlooked.
doi:10.1159/000114005
PMCID: PMC2786012  PMID: 18223306
Acute renal failure, outcomes; Extended facility care; Home health care; Nephrology, clinical
19.  Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors 
Nature neuroscience  2007;10(7):870-879.
Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-specific loss of CB1 substantially reduced the analgesia produced by local and systemic, but not intrathecal, delivery of cannabinoids. We conclude that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects.
doi:10.1038/nn1916
PMCID: PMC2234438  PMID: 17558404
20.  The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons 
Local anesthetics (LAs) block the generation and propagation of action potentials by interacting with specific sites of voltage-gated Na+ channels. LAs can also excite sensory neurons and be neurotoxic through mechanisms that are as yet undefined. Nonspecific cation channels of the transient receptor potential (TRP) channel family that are predominantly expressed by nociceptive sensory neurons render these neurons sensitive to a variety of insults. Here we demonstrated that the LA lidocaine activated TRP channel family receptors TRPV1 and, to a lesser extent, TRPA1 in rodent dorsal root ganglion sensory neurons as well as in HEK293t cells expressing TRPV1 or TRPA1. Lidocaine also induced a TRPV1-dependent release of calcitonin gene–related peptide (CGRP) from isolated skin and peripheral nerve. Lidocaine sensitivity of TRPV1 required segments of the putative vanilloid-binding domain within and adjacent to transmembrane domain 3, was diminished under phosphatidylinositol 4,5-bisphosphate depletion, and was abrogated by a point mutation at residue R701 in the proximal C-terminal TRP domain. These data identify TRPV1 and TRPA1 as putative key elements of LA-induced nociceptor excitation. This effect is sufficient to release CGRP, a key component of neurogenic inflammation, and warrants investigation into the role of TRPV1 and TRPA1 in LA-induced neurotoxicity.
doi:10.1172/JCI32751
PMCID: PMC2157564  PMID: 18172555
21.  Prevalence and trends of selected urologic conditions for VA healthcare users 
BMC Urology  2006;6:30.
Background
Conducted as part of the Urologic Diseases in America project whose aim was to quantify the burden of urologic diseases on the American public, this study focuses on Veterans Health Administration (VHA) users as a special population to supplement data on overall prevalence rates and trends in the United States. Veterans comprise 25% of the male population 18 years or older and contribute substantially to the overall burden of urologic conditions. The objective of this study is to describe the prevalence rates and trends of urologic cancers and selected benign conditions from 1999 to 2002 for VHA users.
Methods
VHA administrative files for 1999 – 2002 and Medicare claims files for the same years were used to identify those who had a diagnosis of qualifying urologic conditions.
Results
Among the conditions evaluated, prostate cancer was listed as a primary diagnosis for 5.4% of VHA users in 2002, followed in decreasing prevalence by erectile dysfunction (2.9%), renal mass (1.5%), interstitial cystitis (1.4%), and prostatitis (1.1%). Age-adjusted rates showed significant increases for renal mass (31%), interstitial cystitis (14%), and erectile dysfunction (8%) between 1999 and 2002. Systematic variations in prevalence rates and trends were observed by age, race/ethnicity, and region. Those in the Western region generally had lower age-adjusted prevalence rates and their increases were also slower than other regions. Addition of Medicare data resulted in large increases (21 to 489%) in prevalence among VHA users, suggesting substantial amount of non-VA urological care provided to VHA users.
Conclusion
Prevalence rates for many urologic diseases increased between 1999 and 2002, which were not entirely attributable to the aging of veterans. This changing urologic disease burden has substantial implications for access to urologic care and treatment capacity, especially in light of the level of urologic care delivered to veterans by Medicare providers outside the VA. Further study on the factors associated with these increases and how they affect the patterns, cost, and quality of care in veterans is needed.
doi:10.1186/1471-2490-6-30
PMCID: PMC1654168  PMID: 17083728

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