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1.  African Americans, hypertension and the renin angiotensin system 
World Journal of Cardiology  2014;6(9):878-889.
African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system (RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.
PMCID: PMC4176798  PMID: 25276290
African American; Blood pressure; Ethnicity; Hypertension; Renin; Angiotensin
2.  Controversies in Timing of Dialysis Initiation and the Role of Race and Demographics 
Seminars in dialysis  2013;26(6):10.1111/sdi.12130.
Dialysis remains the predominant form of renal replacement therapy in the U.S., but the optimal timing for the initiation of dialysis remains poorly defined. Not only clinical factors such as signs/symptoms of uremia, co-existing cardiovascular disease, and presence of diabetes, but also key demographic characteristics including age, gender, race/ethnicity and socioeconomics have all been considered as potential modifying factors in the decision for the timing of dialysis initiation. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) suggests that dialysis be initiated when signs/symptoms attributable to kidney failure such as serositis, acid-base or electrolyte abnormalities, pruritus, poorly controlled volume status or blood pressure, deteriorating nutritional status despite dietary intervention, or cognitive impairment are visible or noted. These signs/symptoms typically occur when the glomerular filtration rate (GFR) is in the range of 5 to 10 ml/min/1.73 m2, although they may occur at higher levels of GFR. We review recent data on the timing of dialysis initiation, their implications for managing patients with late stage CKD, and the important role of considering key demographics in making patient-centered decisions for the timing of dialysis initiation.
PMCID: PMC3836868  PMID: 24102770
Timing dialysis initiation; race; ethnicity; demographics
3.  What should be the blood pressure target for patients with chronic kidney disease? 
Current opinion in cardiology  2013;28(4):10.1097/HCO.0b013e32836208c2.
Purpose of review
Persons with chronic kidney disease (CKD) exhibit a disproportionate burden of elevated blood pressure (BP) with a high prevalence of premature end-stage renal disease and cardiovascular events.
Recent findings
Results of recent randomized controlled clinical trials suggest that most patients with reduced estimated glomerular filtration rate (eGFR) and hypertension experience optimal clinical outcomes when SBP is less than 140 mmHg and DBP is less than 90 mmHg. The benefit of additional lowering of SBP to less than 130 mmHg and DBP to less than 80 mmHg remains controversial, and appears to be of most benefit to the subset of CKD patients with proteinuria (>300 mg/day). The combination of a diuretic and an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) has demonstrated particular promise in patients with reduced eGFR and proteinuria.
A practical approach in clinical practice for the treatment of elevated BP in persons with CKD is to achieve a BP less than 140/90 mmHg with a combination of diuretic and an ARB or ACEI. Consideration for a lower BP goal and other therapeutic and nontherapeutic interventions can be made based on the cause of CKD, presence of proteinuria, or other coexisting medical conditions.
PMCID: PMC3811129  PMID: 23736818
chronic kidney disease; high blood pressure; hypertension
4.  Historically Black Medical Schools: Addressing the Minority Health Professional Pipeline and the Public Mission of Care For Vulnerable Populations 
Substantial changes in not only access to care, cost, and quality of care, but also health professions education are needed to ensure effective national healthcare reform. Since the actionable determinants of health such as personal beliefs and behaviors, socioeconomic factors, and the environment disproportionately affect the poor (and often racial/ethnic minorities), many have suggested that focusing efforts on this population will both directly and indirectly improve the overall health of the nation. Key to the success of such strategies are the ongoing efforts by historically black medical schools (HBMSs) as well as other minority serving medical and health professional schools, who produce a disproportionate percentage of the high-quality and diverse health professionals that are dedicated to maintaining the health of an increasingly diverse nation. Despite their public mission, HBMSs receive limited public support threatening their ability to not only meet the increasing minority health workforce needs but to even sustain their existing contributions. Substantial changes in health education policy and funding are needed to ensure HBMSs as well as other minority-serving medical and health professional schools can continue to produce the diverse, high-quality health professional workforce necessary to maintain the health of an increasingly diverse nation. We explore several model initiatives including focused partnerships with legislative and business leaders that are urgently needed to ensure the ability of HBMSs to maintain their legacy of providing compassionate, quality care to the communities in greatest need.
PMCID: PMC3739050  PMID: 19806842
historically black colleges and universities; minority; health disparities
5.  Vitamin D and Cardiovascular Disease: Potential Role in Health Disparities 
Cardiovascular disease (CVD), which includes coronary artery disease and stroke, is the leading cause of mortality in the nation. Excess CVD morbidity and premature mortality in the African American community is one of the most striking examples of racial/ethnic disparities in health outcomes. African Americans also suffer from increased rates of hypovitaminosis D, which has emerged as an independent risk factor for all-cause and cardiovascular mortality. This overview examines the potential role of hypovitaminosis D as a contributor to racial and ethnic disparities in cardiovascular disease (CVD). We review the epidemiology of vitamin D and CVD in African Americans and the emerging biological roles of vitamin D in key CVD signaling pathways that may contribute to the epidemiological findings and provide the foundation for future therapeutic strategies for reducing health disparities.
PMCID: PMC3417128  PMID: 22102304
VDR; CVD; PAI; Wrch-1; Rho; Fst
6.  Impact of Age, Race and Ethnicity on Dialysis Patient Survival and Kidney Transplantation Disparities 
American journal of nephrology  2014;39(3):183-194.
Prior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups.
The associations between race/ethnicity with all-cause mortality and kidney transplantation were separately examined among 130,909 adult dialysis patients from a large national dialysis organization (entry period 2001-2006, follow-up through 2009) within 7 age categories using Cox proportional hazard models adjusted for case-mix and malnutrition and inflammatory surrogates.
African-Americans had similar mortality vs. whites in younger age groups (18-40 years), but decreased mortality in older age groups (>40 years). In contrast, Hispanics had lower mortality vs. whites across all ages. In sensitivity analyses using competing risk regression to account for differential kidney transplantation rates across racial/ethnic groups, the African-American survival advantage was limited to >60 year old age categories. African-Americans and Hispanics were less likely to undergo kidney transplantation from all donor types vs. whites across all ages, and these disparities were even more pronounced for living donor kidney transplantations (LDKT).
Hispanic dialysis patients have greater survival vs. whites across all ages; in African-Americans, this survival advantage is limited to patients >40 years old. Minorities are less likely to undergo kidney transplantation, particularly LDKT, across all ages.
PMCID: PMC4024458  PMID: 24556752
Race; Ethnicity; Disparities; Survival; Transplantation
7.  Racial Disparities in Kidney Disease Outcomes 
Seminars in nephrology  2013;33(5):409-415.
Chronic kidney disease (CKD) is a national public health problem. While the prevalence of early stages of CKD is similar across different racial/ethnic and socioeconomic groups, the prevalence of end-stage renal disease (ESRD) is greater for minorities than their non-Hispanic white peers. Paradoxically, once on dialysis minorities experience survival rates that exceed their non-Hispanic white peers. Advancing our understanding of the unique interplay of biological, genetic, environmental, socio-cultural, and health care system level factors may prompt reorientation of our approach to health promotion and disease prevention. The potential of this new approach is to create previously unimagined gains to improve patient outcomes and reduce health inequities for patients with CKD.
PMCID: PMC3983362  PMID: 24119846
racial disparities; chronic kidney disease
8.  Role of impaired Nrf2 activation in the pathogenesis of oxidative stress and inflammation in chronic tubulo-interstitial nephropathy 
Nephrology Dialysis Transplantation  2013;28(8):2038-2045.
Tubulo-interstitial nephropathy (TIN) is a common cause of chronic kidney disease (CKD). Consumption of an adenine-containing diet causes the accumulation of 2,8-dihydroxyadenine in the renal tubules triggering intense chronic TIN and progressive CKD in rats. CKD in this model is associated with, and largely driven by, oxidative stress and inflammation. Oxidative stress and inflammation in rats with spontaneous focal segmental glomerulosclerosis and rats with CKD induced by 5/6 nephrectomy are associated with an impaired activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) which is the master regulator of genes encoding many antioxidant and detoxifying enzymes. The effect of TIN on the Nrf2 pathway and its key target genes is unknown and was investigated here.
Sprague-Dawley rats were randomized to control and adenine-treated (rat chow-containing 0.7% adenine for 2 weeks) groups and followed up for 4 weeks.
The adenine-treated animals exhibited marked azotemia, impaired urinary concentrating capacity, intense tubular and glomerular damage, interstitial inflammation and fibrosis. This was associated with an increased expression of NAD(P)H oxidase, cyclooxygenase-2 and 12-lipoxygenase, and activation of NF-κB, the master regulator of pro-inflammatory cytokines and chemokines. Oxidative stress and inflammation in the kidneys of adenine-treated animals was accompanied by an impaired activation of Nrf2 and down-regulation of its target gene products including, catalase, heme oxygenase-1 and glutamate-cysteine ligase.
Chronic TIN is associated with impaired Nrf2 activity which contributes to the pathogenesis of oxidative stress and inflammation and amplifies their damaging effects on the kidney.
PMCID: PMC3765021  PMID: 23512109
antioxidants; chronic kidney disease; CKD progression; reactive oxygen species
9.  Efficacy of a Culturally Congruent HIV Risk-Reduction Intervention for Behaviorally Bisexual Black Men: Results of a Randomized Trial 
AIDS (London, England)  2013;27(12):1979-1988.
Black men who have sex with men and women (MSMW) experience high HIV rates and may not respond to interventions targeting gay-identified men. We tested the efficacy of the Men of African American Legacy Empowering Self (MAALES), a multi-session, small-group, holistically-framed intervention designed to build skills, address sociocultural issues and reduce risk behaviors in Black MSMW.
From 2007–2011, we enrolled 437 Black MSMW into a parallel randomized control trial that compared MAALES to the control condition, a single, individualized HIV risk-reduction session.
Participants completed surveys at baseline, three- and six-months post intervention. We used multiple regressions to compare risk behaviors at follow-up between the intervention and control groups while adjusting for baseline risk behaviors, time between assessments, other covariates, and clustering. We used inverse probability weighting (IPW) to adjust for loss-to-follow-up while carrying out these regressions with the 291 (76.4%) randomized participants who completed at least one follow-up.
Participants were largely low-income (55% reported monthly incomes <$1000); nearly half had previously tested HIV-positive. At six months follow-up, unadjusted within-group analyses demonstrated reduced risk behaviors for the MAALES but not the control group. Adjusted results indicated significant intervention-associated reductions in the numbers of total anal or vaginal sex acts (RR=0.61; 95% CI 0.49, 0.76), unprotected sex acts with females (RR=0.50; 95% CI 0.37, 0.66), and female partners (RR=0.56; 95% CI 0.44, 0.72). Near significant reductions were observed for number of male intercourse partners.
The MAALES intervention was efficacious at reducing HIV risk behaviors in Black MSMW.
PMCID: PMC4096133  PMID: 24180003
HIV Infections/epidemiology/ethnology/*prevention & control; Bisexuality; Risk Reduction Behavior; Black/African American; Homosexuality; African Americans/ethnology/psychology
10.  Association of malnutrition–inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients 
Nephrology Dialysis Transplantation  2012;28(7):1936-1945.
Protein-energy wasting, inflammation and refractory anemia are common in long-term hemodialysis patients. A decreased responsiveness to erythropoiesis-stimulating agents (ESA) is often the cause of the refractory anemia. We hypothesized that the malnutrition–inflammation complex is an independent predictor of decreased responsiveness to ESAs in hemodialysis patients.
This cohort study of 754 hemodialysis patients was examined for an association between inflammatory and nutritional markers, including the malnutrition–inflammation score (MIS) and responsiveness to ESA. Cubic spline models were fitted to verify found associations.
The mean (±SD) age of patients was 54 ± 15 years, 53% were diabetic and 32% blacks. MIS was worse in the highest quartile of ESAs responsiveness index (ERI, ESA dose divided by hemoglobin) when compared with 1st quartile (6.5 ± 4.5 versus 4.4 ± 3.4; P < 0.001). Both C-reactive protein (log CRP) (β = 0.19) and interleukin-6 (log IL-6) (β = 0.32) were strong and independent predictors of ERI using multivariate linear regression. Serum albumin (β = −0.30) and prealbumin levels (β = −0.14) were inversely associated with ERI. Each 1 SD higher MIS, higher CRP and lower albumin were associated with 86, 44 and 97% higher likelihood of having highest versus three lowest ERI quartiles in fully adjusted models [odds ratio (and 95% confidence interval) of 1.86 (1.31–2.85), 1.44 (1.08–1.92) and 1.97 (1.41–2.78)], respectively. Cubic splines confirmed the continuous and incremental nature of these associations.
Malnutrition–inflammation complex is an incremental predictor of poor responsiveness to ESAs in hemodialysis patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management.
PMCID: PMC3707522  PMID: 23045431
erythropoietin-stimulating agent (ESA) therapy; hemoglobin; inflammatory marker; malnutrition–inflammation complex; responsiveness to ESAs
11.  Long-Term Supplementation With a Cystine-Based Antioxidant Delays Loss of Muscle Mass in Aging 
Oxidative stress increases with age and is postulated to be a major causal factor for sarcopenia in aging. Here, we examined whether the administration of a cystine-based antioxidant (F1) can alleviate/delay age-specific changes in skeletal muscles. C57BL6 male mice aged 17 months (middle aged) were fed with normal diet with or without supplementation of F1 (3mg/kg food) for 6 months. Compared with young (5 months old) mice old mice exhibited increased markers of oxidative stress, inflammation, and muscle cell apoptosis and decreased muscle weight. These age-related changes were further associated with inactivation of adenosine-5′-monophosphate–activated protein kinase (AMPK), increased lipogenesis, activation of c-Jun NH2-terminal kinase, and decreased expression of Delta 1, phospho-Akt, and proliferating cell nuclear antigen in aged skeletal muscle. Such alterations were significantly prevented by F1. These results demonstrate the beneficial effects of F1 to attenuate loss of muscle mass associated with aging.
PMCID: PMC3674717  PMID: 23459206
Antioxidant; Mice; Muscle cell apoptosis; Oxidative stress; Sarcopenia.
12.  Racial and Ethnic Differences in Mortality of Hemodialysis Patients: Role of Dietary and Nutritional Status and Inflammation 
American Journal of Nephrology  2011;33(2):157-167.
Racial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities.
In a 6-year (2001–2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines.
In age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (−2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3–3.8) and 4.1-fold (2.2–7.2) higher death risk in Blacks and Whites, respectively.
Significant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.
PMCID: PMC3202917  PMID: 21293117
Black race; Hispanic ethnicity; African Americans; Non-Hispanic White; Nutritional status; Inflammatory markers; Dietary intake; Survival
15.  Follistatin promotes adipocyte differentiation, browning, and energy metabolism[S] 
Journal of Lipid Research  2014;55(3):375-384.
Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.
PMCID: PMC3934723  PMID: 24443561
mouse embryonic fibroblast; myostatin; brown fat; energy expenditure; uncoupling protein 1; mitochondria
16.  Reasons for the lack of salutary effects of cholesterol lowering interventions in ESRD populations 
Blood purification  2013;35(1-3):31-36.
Cardiovascular disease (CVD) is the main cause of premature death in patients with chronic kidney disease (CKD). The underlying mechanisms of CVD in patients with mild to moderate CKD are different from those with end-stage renal disease (ESRD). While serum cholesterol is frequently elevated and contributes to atherosclerosis in many CKD patients particularly those with nephrotic proteinuria, it is usually normal, even subnormal in most ESRD patients receiving hemodialysis. CVD in the ESRD population is primarily driven by oxidative stress, inflammation, accumulation of the oxidation-prone intermediate density lipoproteins (IDL), chylomicron remnants and small dense LDL particles as well as HDL deficiency and dysfunction, hypertension, vascular calcification, and arrhythmias. Only a minority of hemodialysis patients have hypercholesterolemia which is most likely due to genetic or unrelated factors. In addition due to peritoneal losses of proteins which simulate nephrotic syndrome, peritoneal dialysis patients often exhibit hypercholesterolemia. Clearly when present, hypercholesterolemia contributes to CVD in CKD and ESRD population and justifies cholesterol lowering therapy. However the majority of ESRD patients and a subpopulation of CKD patients with minimal proteinuria have normal or subnormal serum cholesterol levels and do not benefit from and can be potentially harmed by statin therapy. In fact the lack of efficacy of statins in hemodialysis patients has been demonstrated in several randomized clinical trials. This review is intended to provide an overview of the mechanisms responsible for the failure of statins to reduce cardiovascular morbidity and mortality in most ESRD patients and to advocate the adoption of individualized care principal in the management of dyslipidemia in this population.
PMCID: PMC3595172  PMID: 23343544
Statins; lipid disorders; cardiovascular disease; progression of kidney disease; hemodialysis; nephrotic syndrome
17.  1,25(OH)2vitamin D3 Enhances Myogenic Differentiation by Modulating the Expression of Key Angiogenic Growth factors and Angiogenic Inhibitors in C2C12 Skeletal Muscle Cells 
Vitamin D is mostly recognized for its regulation of calcium homeostasis in relation to the intestine, kidney, and bone. Although clinical studies have linked vitamin D with increased muscle function and strength, little is known of its underlying molecular mechanism. We recently demonstrated that 1,25-D3 exerts a direct pro-myogenic effect on skeletal muscle cells; this has provoked our investigation of 1,25-D’s effect on angiogenesis, a vital process for new capillary development and tissue repair. In this study, we examined the mechanism by which 1,25-D3 modulates key angiogenic growth factors and angiogenic inhibitors. C2C12 myoblasts were incubated with 100 nM 1,25-D3 or placebo for 1, 4 and 10 days. At the end of the respective incubation time, total RNA was isolated for PCR arrays and for qRT-PCR. Total proteins were isolated for western blots and proteome profiler arrays. The addition of 1,25-D3 to C2C12 myoblasts increased VEGFa and FGF-1: two pro-angiogenic growth factors that promote neo-vascularization and tissue regeneration, and decreased FGF-2 and TIMP-3: two myogenic and/or angiogenic inhibitors. Our previous study demonstrated that 1,25-D3 altered IGF-I/II expression, consistent with the observed changes in VEGFa and FGF-2 expression. These results extend our previous findings and demonstrate the modulation of angiogenesis which may be an additional mechanism by which 1,25-D3 promotes myogenesis. This study supports the mechanistic rationale for assessing the administration of vitamin D and/or vitamin D analogues to treat select muscle disorders and may also provide an alternative solution for therapies that directly manipulate VEGF and FGF’s to promote angiogenesis.
PMCID: PMC3513642  PMID: 22982629
19.  Donor Race and Outcomes in Kidney Transplant Recipients 
Clinical transplantation  2012;27(1):37-51.
African Americans are at greater risk to reach end stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.
Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13,692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR] and 95% CI) and logistic regression, respectively.
Patients were 48±14 years old and included 39% women and 26% diabetics. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with hazard ratios of 1.39 (1.09–1.78) for all-cause mortality, 1.80 (1.17–2.76) for cardiovascular mortality, 1.30 (1.03–1.64) for death-censored graft loss and 1.31 (1.10–1.57) for combined outcome over the 6-year observation period. In the non-African American recipient sub-cohort, but not in the African American recipient sub-cohort, African American donor race was associated with higher risk of death-censored graft loss (2.24(1.44–3.49)) in our fully adjusted model.
African American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.
PMCID: PMC3593049  PMID: 22830989
Donor race/ethnicity; kidney transplantation; malnutrition-inflammation complex; mortality; cardiovascular death; graft failure; delayed graft function
20.  Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans 
Archives of internal medicine  2008;168(8):10.1001/archinte.168.8.832.
Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD.
Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death.
During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2).
Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term.
PMCID: PMC3870204  PMID: 18443258
21.  Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients (AIONID) study: results of the pilot-feasibility, double-blind, randomized, placebo-controlled trial 
Low serum albumin is common and associated with protein-energy wasting, inflammation, and poor outcomes in maintenance hemodialysis (MHD) patients. We hypothesized that in-center (in dialysis clinic) provision of high-protein oral nutrition supplements (ONS) tailored for MHD patients combined with anti-oxidants and anti-inflammatory ingredients with or without an anti-inflammatory appetite stimulator (pentoxifylline, PTX) is well tolerated and can improve serum albumin concentration.
Between January 2008 and June 2010, 84 adult hypoalbuminemic (albumin <4.0 g/dL) MHD outpatients were double-blindly randomized to receive 16 weeks of interventions including ONS, PTX, ONS with PTX, or placebos. Nutritional and inflammatory markers were compared between the four groups.
Out of 84 subjects (mean ± SD; age, 59 ± 12 years; vintage, 34 ± 34 months), 32 % were Blacks, 54 % females, and 68 % diabetics. ONS, PTX, ONS plus PTX, and placebo were associated with an average change in serum albumin of +0.21 (P = 0.004), +0.14 (P = 0.008), +0.18 (P = 0.001), and +0.03 g/dL (P = 0.59), respectively. No related serious adverse events were observed. In a predetermined intention-to-treat regression analysis modeling post-trial serum albumin as a function of pre-trial albumin and the three different interventions (ref = placebo), only ONS without PTX was associated with a significant albumin rise (+0.17 ± 0.07 g/dL, P = 0.018).
In this pilot-feasibility, 2 × 2 factorial, placebo-controlled trial, daily intake of a CKD-specific high-protein ONS with anti-inflammatory and anti-oxidative ingredients for up to 16 weeks was well tolerated and associated with slight but significant increase in serum albumin levels. Larger long-term controlled trials to examine hard outcomes are indicated.
Electronic supplementary material
The online version of this article (doi:10.1007/s13539-013-0115-9) contains supplementary material.
PMCID: PMC3830006  PMID: 24052226
Albumin; Hypoalbuminemia; Inflammation; Protein intake; Hemodialysis; Oral nutrition supplements; Anti-oxidant ingredients; Anti-inflammatory ingredients
22.  Patient Care Staffing Levels and Facility Characteristics in U.S. Hemodialysis Facilities 
Higher numbers of registered nurses per patient have been associated with improved patient outcomes in acute care facilities. Variation and associations of patient-care staffing levels and hemodialysis facility characteristics have not been previously examined.
Study Design
Cross-sectional study using Poisson regression to examine associations betwee patient-care staffing levels and hemodialysis facility characteristics.
Setting & Participants
4,800 U.S. hemodialysis facilities in the 2009 CMS ESRD Annual Facility Survey (CMS-2744), USRDS.
Facility characteristics, including profit status, freestanding status, chain affiliatio and geographic region, adjusted for facility size, capacity, functional type, and urbanicity.
Patient care staffing levels, including ratios of Registered Nurses (RN), Licensed Practical Nurses (LPN), Patient Care Technicians (PCT), composite staff (RN+LPN+PCT), Social Workers, and Dietitians to in-center hemodialysis patients.
After adjusting for background facility characteristics, the ratios of RNs and LPNs to patients were 35% (p<0.001) and 42% (p<0.001) lower, but the PCT-to-patient ratio was 16% (p<0.001) higher in for-profit facilities than those in nonprofit facilities (Rate ratio, 0.65, 95%CI, 0.63–0.68; 0.58, 0.51–0.65; 1.16, 1.12–1.19; respectively). Regionally, compared to the Northeast, the adjusted RN-to-patient ratio was 14% (p< 0.001) lower in the Midwest, 25% (p< 0.001) lower in the South, and 18% (p< 0.001) lower in the West. Even after additional adjustments, the large for-profit chains had significantly lower RN and LPN ratios than the largest nonprofit chain, but a significantly higher PCT-to-patient ratio. The overall composite staffing levels were also lower in for-profit and chain-affiliated facilities. The patterns hold when the hospital-based units were excluded.
Nursing hours were not available.
The significant variation in patient-care staffing levels and its associations with facility characteristics warrants inclusion in future large-scale hemodialysis outcomes studies. ESRD networks and hemodialysis facilities should attend to quality assurance and performance improvement initiatives that maximize licensed nurse-staffing levels in hemodialysis facilities.
PMCID: PMC3840051  PMID: 23810689
USRDS; in-center hemodialysis; CMS ESRD Facility survey; staffing ratios; profit; region
23.  Baseline Predictors of Renal Disease Progression in the African American Study of Hypertension and Kidney Disease 
Journal of the American Society of Nephrology : JASN  2006;17(10):10.1681/ASN.2005101101.
Patients with chronic kidney disease have an increased risk for progression to ESRD. The purpose of this study was to examine factors that predict increased risk for adverse renal outcomes. Cox regression was performed to assess the potential of 38 baseline risk factors to predict the clinical renal composite outcome of 50% or 25-ml/min per 1.73 m2 GFR decline or ESRD among 1094 black patients with hypertensive nephrosclerosis (GFR 20 to 65 ml/min per 1.73 m2). Patients were trial participants who had been randomly assigned to one of two BP goals and to one of three antihypertensive regimens and followed for a range of 3 to 6.4 yr. In unadjusted and adjusted analyses, baseline proteinuria was consistently associated with an increased risk for adverse renal outcomes, even at low levels of proteinuria. The relationship of proteinuria with adverse renal outcomes also was evident in analyses that were stratified by level of GFR, which itself was associated with adverse renal outcomes but only at levels <40 ml/min. Other factors that were significantly associated with increased renal events after adjustment for baseline GFR, age, and gender, both with and without adjustment for baseline proteinuria, included serum creatinine, urea nitrogen, and phosphorus. In black patients with hypertensive nephrosclerosis, increased proteinuria, reduced GFR, and elevated levels of serum creatinine, urea nitrogen and phosphorus were directly associated with adverse clinical renal events. These findings identify a subset of this high-risk population that might benefit from even more aggressive treatment.
PMCID: PMC3833081  PMID: 16959828
24.  Chronic kidney disease, hypovitaminosis D, and mortality in the United States 
Kidney international  2009;76(9):977-983.
Low serum 25-hydroxy vitamin D (25OHD) predicts a higher cardiovascular risk in the general population. Because patients with chronic kidney disease are more likely to have low serum 25OHD, we determined the relationship between hypovitaminosis D and death in this group. Analysis was done using a cohort composed of 3011 patients from the Third National Health and Nutrition Examination Survey who had chronic kidney disease but were not on dialysis and who had a mean follow-up of 9 years. In analyses adjusted for demographics, cardiovascular risk factors, serum phosphorus, albumin, hemoglobin, stage of chronic kidney disease, albuminuria, and socioeconomic status, individuals with serum 25OHD levels less than 15 ng/ml had an increased risk for all-cause mortality when compared to those with levels over 30 ng/ml. This significantly higher risk for death with low serum 25OHD was evident in 15 of the 23 subgroups. The higher risk for cardiovascular and non-cardiovascular mortality became statistically nonsignificant on multivariable adjustment. The trend for higher mortality in patients with 25OHD levels 15–30 ng/ml was not statistically significant. Our results indicate there is a graded relationship between serum 25OHD and the risk for death among subjects with chronic kidney disease who are not undergoing dialysis. Randomized, controlled trials are needed to conclusively determine whether vitamin D supplementation reduces mortality.
PMCID: PMC3791220  PMID: 19657329
cardiovascular; chronic kidney disease; mortality; non-cardiovascular; vitamin D
25.  The Healthy African American Families (HAAF) Project: From Community-Based Participatory Research To Community-Partnered Participatory Research 
Ethnicity & disease  2010;20(1 0 2):S2-1-8.
During the past two decades, there has been an increased use of community-based participatory research in public health activities, especially as part of efforts to understand health disparities affecting communities of color. This article describes the history and lessons learned of a long-standing community participatory project, Healthy African American Families (HAAF), in Los Angeles, California. HAAF evolved from a partnership formed by a community advisory board, university, and federal health agency to an independent, incorporated community organization that facilitates and brokers research and health promotion activities within its community. HAAF created mechanisms for community education and networks of community relationships and reciprocity through which mutual support, research, and interventions are integrated. These sustained, institutionalized relationships unite resources and both community and scientific expertise in a community-partnered participatory research model to address multiple health problems in the community, including preterm birth, HIV, asthma, depression, and diabetes. The HAAF participatory process builds on existing community resiliency and resources and on centuries of self-help, problem-solving, cooperative action, and community activism within the African American community. HAAF demonstrates how community-partnered participatory research can be a mechanism for directing power, collective action, system change, and social justice in the process of addressing health disparities at the community level.
PMCID: PMC3791221  PMID: 20629240
Community-based Participatory Research; Community-partnered Participatory Research; African American; Family

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