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.
cardiovascular; chronic kidney disease; mortality; non-cardiovascular; vitamin D
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.
Community-based Participatory Research; Community-partnered Participatory Research; African American; Family
Hypovitaminosis D is an important public health problem. Serum 25-hydroxyvitamin D (25-OHD) is now recognized as an independent predictor for cardiovascular and related diseases (CVD) as well as other chronic medical conditions. However, the biologic pathways through which these effects are mediated remain poorly understood. We hypothesized that exposing mesenchymal multipotent cells (MMCs) to the active form of vitamin D would increase the expression of selected antifibrotic factors that in turn would ameliorate the progression of chronic diseases. MMCs were primed with 5′-azacytidine to induce a fibrotic phenotype and then treated with active vitamin D (1,25D) or ethanol <0·1% as vehicle in a time course manner (30 min, 1, 5, and 24 h, and for 4 and 7 days). The addition of 1,25D to MMCs promotes: a) increased expression and nuclear translocation of the vitamin D receptor; b) decreased expression of TGFB1 and plasminogen activator inhibitor (SERPINE1), two well-known profibrotic factors; c) decreased expression of collagen I, III and other collagens isoforms; and d) increased expression of several antifibrotic factors such as BMP7 a TGFB1 antagonist, MMP8 a collagen breakdown inducer and follistatin, an inhibitor of the profibrotic factor myostatin. In conclusion, the addition of 1,25D to differentiated MMCs displays a decreased profibrotic signaling pathway and gene expression, leading to decrease in collagen deposition. This study highlights key mechanistic pathways through which vitamin D decreases fibrosis, and provides a rationale for studies to test vitamin D supplementation as a preventive and/or early treatment strategy for CVD and related fibrotic disorders.
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.
VDR; CVD; PAI; Wrch-1; Rho; Fst
Chronic kidney disease (CKD) is a public health problem, mediated by hemodynamic and non-hemodynamic events including oxidative stress. We investigated the effect of two glutathione (GSH) precursors, N-acetyl-cysteine (NAC) and cystine as the physiologic carrier of cysteine in GSH with added selenomethionine (F1) in preventing spermine (uremic toxin) induced apoptosis in cultured human aortic vascular smooth muscle cells (VSMC). VSMCs exposed to spermine (15 μM) with or without antioxidants (dose 50, 100, 200 and 500 μg/ml) were assessed for apoptosis, c-Jun-NH2-terminal kinase (JNK) activation and inducible nitric oxide synthase (iNOS) induction, and activation of intrinsic pathway signaling. Spermine exposure resulted in activation of JNK and iNOS induction, and apoptosis. NAC and F1 (dose range 50–500 μg/ml) attenuated spermine-induced acceleration of VSMC apoptosis, but only F1 (at 200 and 500 μg/ml) maintained spermine-induced apoptosis at control levels. Spermine-induced JNK activation was prevented by 200 μg/ml of both NAC and F1, while iNOS induction was blocked only by F1. Notably, the adverse effects of spermine on BAX/BCL-2 ratio, cytochrome c release, and caspase activation was fully attenuated by F1. In conclusion, F1 was more effective than NAC in preventing spermine-induced apoptosis and downstream changes in related signal transduction pathways in VSMCs. Further studies are needed to examine the effect of these compounds in preventing CKD-associated vascular disease.
Spermine; Apoptosis; vascular smooth muscle cells; antioxidants; chronic kidney disease
Uninsured adults in the United States have poor access to health care services and worse health outcomes than insured adults. Little is known about the association between lack of insurance and chronic kidney disease (CKD) progression to end-stage renal disease (ESRD) or death in patients at high risk of kidney disease. We used 2000–2011 data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) to examine this association.
The study population included KEEP participants younger than 65 years. Outcomes were time to ESRD (chronic kidney failure treated by renal replacement therapy) and time to death. Incident ESRD was ascertained by linkage to the US Renal Data System, and vital status, by linkage to the Social Security Administration Death Master File. We used Cox proportional hazard regression to examine the association between insurance and risk of death or ESRD after adjusting for demographic variables.
Of 86,588 participants, 27.8% had no form of insurance, 10.3% had public insurance, and 61.9% had private insurance; 15.0% had CKD (defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urine albumin-creatinine ratio ≥30 mg/g), 63.3% had hypertension, and 27.7% had diabetes. Of participants with CKD, 29.3% had no health insurance. Participants without insurance were younger, more likely to be Hispanic and to have 12 or fewer years of education, and less likely to have seen a physician in the past year. After adjustment for demographic characteristics, uninsured KEEP participants were 82% more likely than privately insured participants to die (HR, 1.82; 95% CI, 1.56–2.12; P < 0.001) and 72% more likely to develop ESRD (HR, 1.72; 95% CI, 1.33–2.22; P < 0.001). The association between insurance and outcomes varied by CKD stage.
Lack of insurance is an independent risk factor for early death and ESRD in this population at high risk of kidney disease. Considering the high morbidity and mortality and increasing cost associated with ESRD, access to appropriate health insurance coverage is warranted.
Chronic kidney disease; end-stage renal disease; health insurance; mortality; public health
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.
historically black colleges and universities; minority; health disparities
Just as scientific articles are used as a way of sharing knowledge in scientific communities, stories are used as a way of transferring knowledge within African American communities. This article uses the story and metaphor of Stone Soup to illustrate the Healthy African American Families' (HAAF) Community Partnered Participatory Research (CPPR) method of engaging diverse partners to address health issues, such as preterm birth, depression, diabetes, and kidney disease, and to create community-wide change through education, capacity building, resource sharing, and intervention development.
African American; Family; Community Partnered Participatory Research
Both anemia and secondary hyperparathyroidism are reflections of hormonal failure in chronic kidney disease (CKD). While the association of elevated levels of parathyroid hormone (PTH) and anemia has been studied among those with advanced CKD, less is known about this association in mild-to-moderate CKD.
In a cross-sectional analysis, the relationship between PTH and hemoglobin levels was investigated in 10,750 participants in the National Kidney Foundation's Kidney Early Evaluation Program with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.
In the unadjusted analysis, higher PTH levels were associated with lower hemoglobin levels. However, after multivariable adjustment for age, race, gender, smoking status, education, cardiovascular disease, diabetes, hypertension, cancer, albuminuria, BMI, baseline eGFR, calcium, and phosphorus, the direction of association changed. As compared to the first PTH quintile, hemoglobin levels were 0.09 g/dl (95% CI: 0.01-0.18), 0.15 g/dl (95% CI: 0.07-0.24), 0.18 g/dl (95% CI: 0.09-0.26), and 0.13 g/dl (95% CI: 0.07-0.25) higher for the second, third, fourth, and fifth quintiles, respectively. Similarly, each standard deviation increase in natural log transformed PTH was associated with a 0.06 g/dl (95% CI: 0.03-0.09, p = 0.0003) increase in hemoglobin. However, a significant effect modification was seen for diabetes (p = 0.0003). Each standard deviation increase in natural log transformed PTH was associated with a 0.10 g/dl (95% CI: 0.054-0.138, p < 0.0001) increase in hemoglobin, while no association was seen among those without diabetes mellitus.
After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.
Chronic kidney disease; Anemia; Secondary hyperparathyroidism
Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular mortality, but little is known about the association between physician utilization and cardiovascular disease risk-factor control in patients with CKD. We used 2005–2010 data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) to examine this association at first and subsequent screenings.
Control of risk factors was defined as control of blood pressure, glycemia, and cholesterol levels. We used multinomial logistic regression to examine the association between participant characteristics and seeing a nephrologist after adjusting for kidney function and paired t tests or McNemar tests to compare characteristics at first and second screenings.
Of 90,009 participants, 61.3% had a primary care physician only, 2.9% had seen a nephrologist, and 15.3% had seen another specialist. The presence of 3 risk factors (hypertension, diabetes, and hypercholesterolemia) increased from 26.8% in participants with CKD stages 1–2 to 31.9% in those with stages 4–5. Target levels of all risk factors were achieved in 7.2% of participants without a physician, 8.3% of those with a primary care physician only, 9.9% of those with a nephrologist, and 10.3% of those with another specialist. Of up to 7,025 participants who met at least one criterion for nephrology consultation at first screening, only 12.3% reported seeing a nephrologist. Insurance coverage was associated strongly with seeing a nephrologist. Of participants who met criteria for nephrology consultation, 406 (5.8%) returned for a second screening, of whom 19.7% saw a nephrologist. The percentage of participants with all risk factors controlled was higher at the second screening (20.9% vs 13.3%).
Control of cardiovascular risk factors is poor in the KEEP population. The percentage of participants seeing a nephrologist is low, although better after the first screening. Identifying communication barriers between nephrologists and primary care physicians may be a new focus for KEEP.
Cardiovascular disease risk factors; chronic kidney disease; nephrologist care; primary care
There are counterintuitive but consistent observations that African American maintenance dialysis patients have greater survival despite their less favorable socioeconomic status, high burden of cardiovascular risks including hypertension and diabetes, and excessively high chronic kidney disease prevalence. The fact that such individuals have a number of risk factors for lower survival and yet live longer when undergoing dialysis treatment is puzzling. Similar findings have been made among Israeli maintenance dialysis patients, in that those who are ethnically Arab have higher end-stage renal disease but exhibit greater survival than Jewish Israelis. The juxtaposition of these two situations may provide valuable insights into racial/ethnic-based mechanisms of survival in chronic diseases. Survival advantages of African American dialysis patients may be explained by differences in nutritional status, inflammatory profile, dietary intake habits, body composition, bone and mineral disorders, mental health and coping status, dialysis treatment differences, and genetic differences among other factors. Prospective studies are needed to examine similar models in other countries and to investigate the potential causes of these paradoxes in these societies. Better understanding the roots of racial/ethnic survival differences may help improve outcomes in both patients with chronic kidney disease and other individuals with chronic disease states.
African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy.
Obesity is a known cardiometabolic risk factor in children. In adults, pulse pressure (PP) is a known predictor and a risk factor of cardiovascular (CV) diseases. In this study, we examined the association between measures of obesity and PP in children.
A retrospective analysis of 4667 children ages 6–17 years from the National Health and Nutrition Survey (1988–1994) was performed. We defined wide PP as 4th quartile PP and high waist circumference (WC) as >75th percentile based on age and gender.
There were 51% boys, 74% whites, 16% blacks, 10% Hispanics, 12% obese, 26% with high WC, 26% with wide PP, and 9% with high blood pressure (BP). Prevalence of wide PP was high among obese children. A significantly higher mean PP was observed in boys, Blacks, obese, those with high WC and high BP. The adjusted odds ratio (OR) for wide PP was higher in boys, Blacks, and those with high WC.
There was a statistically significant independent association observed between wide PP and high WC, but not with obesity based on BMI. Further exploration of wide PP as a CV risk factor in childhood and its relationship to CV outcomes appears warranted.
Body mass index; waist circumference; blood pressure; cardiovascular risk factors
Background: Cell-cell communication occurs via a variety of mechanisms, including long distances (hormonal), short distances (paracrine and synaptic) or direct coupling via gap junctions, antigen presentation, or ligand-receptor interactions. We evaluated the possibility of neuro-hormonal independent, non-diffusible, physically disconnected pathways for cell-cell communication using dorsal root ganglion (DRG) neurons. Methods: We assessed intracellular calcium ([Ca2+]) in primary culture DRG neurons that express ATP-sensitive P2X3, capsaicinsensitive TRPV1 receptors modulated by estradiol. Physically disconnected (dish-in-dish system; inner chamber enclosed) mouse DRG were cultured for 12 hours near: a) media alone (control 1), b) mouse DRG (control 2), c) human neuroblastoma SHSY-5Y cells (cancer intervention), or d) mouse DRG treated with KCl (apoptosis intervention). Results: Chemosensitive receptors [Ca2+]i signaling did not differ between control 1 and 2. ATP (10 μM) and capsaicin (100nM) increased [Ca2+]i transients to 425.86 + 49.5 nM, and 399.21 ± 44.5 nM, respectively. 17β-estradiol (100 nM) exposure reduced ATP (171.17 ± 48.9 nM) and capsaicin (175.01±34.8 nM) [Ca2+]i transients. The presence of cancer cells reduced ATP- and capsaicin-induced [Ca2+]i by >50% (p<0.05) and abolished the 17β-estradiol effect. By contrast, apoptotic DRG cells increased initial ATP-induced [Ca2+]i, flux four fold and abolished subsequent [Ca2+]i, responses to ATP stimulation (p<0.001). Capsaicin (100nM) induced [Ca2+]i responses were totally abolished. Conclusion: The local presence of apoptotic DRG or human neuroblastoma cells induced differing abnormal ATP and capsaicin-mediated [Ca2+]i fluxes in normal DRG. These findings support physically disconnected, non-diffusible cell-to-cell signaling. Further studies are needed to delineate the mechanism(s) of and model(s) of communication.
Cell-cell communication; TRPV1; P2X3; DRG; SH-SY5Y
Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors.
This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000–2008, with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, not on regular dialysis, and without previous kidney transplant. Albuminuria (urine albumin-creatinine ratio [ACR] ≥ 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region.
Albuminuria prevalence was 8% (n = 2303) in whites, 11% (n = 2310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted odds ratio 1.93, 95% confidence interval 1.70–2.20), then Asians (1.42, 1.26–1.61), African Americans (1.38, 1.29–1.47), and Hispanics (1.19, 1.08–1.31).
In the KEEP study population, albuminuria prevalence was higher among African Americans, Hispanics, Asians, and American Indians/Alaska Natives than among non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially among people at increased risk, in the community primary care setting.
In maintenance hemodialysis (HD) patients, overweight and obesity are associated with survival advantages. Given greater survival of minority maintenance HD patients, we hypothesized that elevated body mass index (BMI) is more strongly associated with lower mortality among Blacks and Hispanics relative to non-Hispanic whites.
Retrospective, cohort study.
Setting and participants
We examined a 6 year (2001–2007) cohort of 109,605 maintenance HD patients including 39,090 Blacks, 17,417 Hispanics and 53,098 non-Hispanic white maintenance HD outpatients from DaVita dialysis clinics. Cox proportional hazards models examined the association between BMI and survival.
Race and BMI.
All cause mortality.
Patients were (mean±SD) 62±15 years old and included 45% women and 45% diabetics. Across 10 a priori selected BMI categories (<18 to ≥40 kg/m2) higher BMI was associated with greater survival in all 3 racial/ethnic groups. Hispanic and Black patients, however, experienced consistently higher survival gains compared to non-Hispanic Whites across almost all BMI categories. Hispanics in the ≥40 kg/m2 category had the lowest death hazard ratio (HR, 0.57; 95% confidence interval [CI], 0.49–0.68) compared to non-Hispanic Whites in the 21.5-<23 kg/m2 group (reference category). While the inverse association was observed for all subgroups, Black maintenance HD patients exhibited the largest decline in death HR with increasing BMI.
Race and ethnicity categories were based on self-identified data.
Whereas survival advantage of high BMI is consistent across all racial/ethnic groups, Black maintenance HD patients had the strongest association of high BMI with improved survival.
obesity; survival; hemodialysis; race; non-Hispanic white; Black; Hispanic
Black-white disparities in mortality persist after adjustment for socioeconomic status and health behaviors. We examined whether allostatic load, the physiological profile influenced by repeated or chronic life stressors, is associated with black-white mortality disparities independent of traditional sociobehavioral risk factors.
We studied 4515 blacks and whites aged 35 to 64 years from the third National Health and Nutrition Examination Survey (1988–1994), using the linked mortality file, to ascertain participant deaths through 2006. We estimated unadjusted sex-specific black-white disparities in cardiovascular/diabetes-related mortality and noninjury mortality. We constructed baseline allostatic load scores based on 10 biomarkers and examined attenuation of mortality disparities in 4 sets of sex-stratified multivariate models, sequentially adding risk factors: (1) age/clinical conditions, (2) socioeconomic status (SES) variables, (3) health behaviors, and (4) allostatic load.
Blacks had higher allostatic load scores than whites; for men, 2.5 vs 2.1, p < .01; and women, 2.6 vs 1.9, p < .01. For cardiovascular/diabetes-related mortality among women, the magnitude of the disparity after adjustment for other risk factors (hazard ratio [HR], 1.63; 95% confidence interval [CI], 0.96–2.75) decreased after adjustment for allostatic load (HR, 1.15; 95% CI, 0.70–1.88). For noninjury mortality among women, the magnitude of the disparity after adjustment for other risk factors (HR, 1.43; 95% CI, 1.00–2.04) also decreased after adjustment for allostatic load (HR, 1.26; 95% CI, 0.90–1.78). For men, disparities were attenuated but persisted after adjustment for allostatic load.
Allostatic load burden partially explains higher mortality among blacks, independent of SES and health behaviors. These findings underscore the importance of chronic physiologic stressors as a negative influence on the health and lifespan of blacks in the United States.
stress; mortality; African Americans
Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.
We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16 129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP≥150 or DBP≥90 mm Hg).
The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74–1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21–2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51–4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88–1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02–1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33–2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00–2.07] for PP≥80 mm Hg compared with PP<50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP≥150 mm Hg or DBP≥90 mm Hg), mostly due to isolated systolic hypertension (54%).
In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.
Recent reports have suggested a close relationship between education and health, including mortality, in the United States.
Setting and Participants
We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP).
Self-reported educational attainment
Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality
We evaluated the cross-sectional associations between self-reported educational attainment with the chronic diseases listed above using logistic regression models adjusted for demographics, access to care, behaviors, and co-morbidities. The association of educational attainment with survival was determined by multivariable Cox proportional hazards regression.
Higher educational attainment was associated with lower prevalence of each of the chronic conditions listed above. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of reduced kidney function to 37% lower odds of cardiovascular disease. Over a mean follow-up time of 3.9 years (median, 3.7 years), 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had a 24% lower mortality, compared to participants who had completed at least some high school.
A lack of income data does not allow us to disentangle the independent effects of education from income.
In this diverse, contemporary cohort, higher educational attainment was independently associated with lower prevalence of chronic diseases and short-term mortality among all age and race/ethnicity groups.
education; mortality; chronic kidney disease
Oxidative stress and inflammation promote the development and progression of chronic kidney disease. Oxidative stress is associated with depletion of tissue glutathione (GSH), the most abundant endogenous intracellular antioxidant, but degradation of oral GSH by digestive enzymes limits its therapeutic use. We hypothesized that GSH repletion with F1, a novel oral GSH precursor containing cystine as a cysteine carrier, would restore tissue GSH and attenuate oxidative stress and inflammation, and thereby reduce the severity of interstitial nephropathy in chronic renal failure (CRF).
Male Sprague-Dawley rats (n=5-8) were assigned to 3 groups: Control (regular rat chow), CRF (rat chow containing 0.7% adenine), and F1-treated CRF (rat chow containing 0.7% adenine and F1, 0.5g/kg/day) for 2-weeks. Animals were switched to regular chow and euthanized after 2 additional weeks.
Consumption of 0.7% adenine-containing diet caused azotemia; severe kidney swelling; heavy tubular and glomerular damage; massive tubulointerstitial nephropathy; impaired urinary concentrating capacity; severe anemia; increased markers of oxidative stress, plasma oxidized glutathione disulfide (GSSG); reduced GSH/GSSG ratio and manganese superoxide dismutase; increased expression of inflammatory mediators (cyclooxygenase-2, cytoplasmic NF-κB, p-IκBα, nuclear NF-κB p65), and 3-nitrotyrosine, p<0.05. Co-treatment with F1 significantly attenuated tubulointerstitial inflammation and edema, improved urinary concentrating capacity, azotemia and anemia, and normalized markers of tissue oxidative and nitrosative stress, p<0.05.
The novel oxidative stress modulator, F1, markedly attenuated oxidative stress indicators, inflammation, renal injury and dysfunction in the rat model of CRF. Studies to determine the effects of F1 in other models of acute and CRF are warranted.
Glutathione precursor; oxidative stress modulator; inflammation; glutathione disulfide; p-IκBα; NF-κB; NF-κB p65; hematocrit
Observational studies indicate greater survival in African American and Hispanic maintenance hemodialysis (HD) patients compared to their Non-Hispanic White counterparts, even though Blacks have shorter life expectancy than Whites in the general population. We hypothesized that this apparent survival advantage is due to a more favorable nutritional/inflammatory profile in minority HD patients.
We examined the association between race/ethnicity and 5-year survival before and after adjustment for case-mix and surrogates of the malnutrition-inflammation complex syndrome (MICS), using Cox regression with or without matched sampling in a large cohort of adult HD patients.
Setting and Participants
124,029 adult HD patients including 16% Hispanics, 49% non-Hispanic whites, and 35% African Americans.
Race/ethnicity before and after adjustment for MICS including BMI, serum albumin, TIBC, ferritin; creatinine, phosphorus, calcium, bicarbonate, white blood cell count, lymphocyte percentage, hemoglobin and protein intake.
5-year (7/2001–6/2006) survival
Among dialysis patients, Blacks and Hispanics had lower mortality overall than Non-Hispanic Whites after traditional case-mix adjustment. However, after additional control for MICS, Hispanics had mortality similar to non-Hispanic whites and African American had ever higher mortality. The unadjusted, case-mix and MICS adjusted hazard ratios (and 95% confidence intervals) of African American vs. Whites in the unmatched cohort were 0.68 (0.66–0.69), 0.89 (0.86–0.91) and 1.06 (1.03–1.09), and in the matched cohort 0.95 (0.90–0.99), 0.89 (0.84–0.94) and 1.16 (1.07–1.26), respectively; and for Hispanics vs. Whites in the unmatched cohort were 0.66 (0.64–0.69), 0.84 (0.81–0.87) and 0.97 (0.94–1.00), and in the matched cohort 0.89 (0.84–0.95), 0.88 (0.83–0.95) and 0.98 (0.91–1.06), respectively.
Unmeasured confounders cannot be adjusted for.
Survival advantages of African American and Hispanic HD patients may be related to differences in nutritional and inflammatory status. Further studies are required to explore these differences.
Race; Hispanic paradox-within-paradox; malnutrition-inflammation-complex syndrome; racial disparities
The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.
Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m2. Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.
The prevalence of eGFRCKD-EPI <60 mL/min/1.73 m2 was 14.3% compared with 16.8% using eGFRMDRD. Using eGFRCKD-EPI, 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m2 using both equations, those with eGFRCKD-EPI of 60-89 mL/min/1.73 m2 had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).
The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.
Chronic kidney disease; glomerular filtration rate estimation; mortality; risk factors
Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low-risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.
In this cross-sectional study, we used data collected from 2000 to 2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.
Of 26,213 participants with CKD based on eGFRMDRD, 23,572 (90%) were also classified with CKD based on eGFRCKD-EPI. Based on eGFRMDRD, 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with Stages 1-5, respectively. Based on eGFRCKD-EPI, 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with Stages 1-5, respectively. Reclassification to a less advanced CKD stage with eGFRCKD-EPI was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFRCKD-EPI.
Using eGFRCKD-EPI led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.
awareness; chronic kidney disease; CKD-EPI; estimated glomerular filtration rate
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.
Black race; Hispanic ethnicity; African Americans; Non-Hispanic White; Nutritional status; Inflammatory markers; Dietary intake; Survival