Longitudinal Pilot Evaluation of the Gut Microbiota Comparing Patients With and Without Chronic Kidney Disease.

OBJECTIVE: The gut microbiota contributes to metabolic diseases, such as diabetes and hypertension, but is poorly characterized in chronic kidney disease (CKD). DESIGN AND METHODS: We enrolled 24 adults within household pairs, in which at least one member had self-reported kidney disease, diabetes, or hypertension. CKD was classified based on estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine-albumin-to-creatinine ratio of ≥ 30 mg/g. Participants collected stool and dietary recalls seasonally over a year. Gut microbiota was characterized using 16s rRNA and metagenomic sequencing. RESULTS: Ten participants had CKD (42%) with a median (interquartile range) estimated glomerular filtration rate of 49 (44, 54) mL/min/1.73 m2. By 16s rRNA sequencing, there was moderate to high intraclass correlation (ICC = 0.63) for seasonal alpha diversity (Shannon index) within individuals and modest differences by season (P < .01). ICC was lower with metagenomics, which has resolution at the species level (ICC = 0.26). There were no differences in alpha or beta diversity by CKD with either method. Among 79 genera, Frisingicoccus, Tuzzerella, Faecalitalea, and Lachnoclostridium had lower abundance in CKD, while Collinsella, Lachnospiraceae_ND3007, Veillonella, and Erysipelotrichaceae_UCG_003 were more abundant in CKD (each nominal P < .05) using 16s rRNA sequencing. Higher Collinsella and Veillonella and lower Lachnoclostridium in CKD were also identified by metagenomics. By metagenomics, Coprococcus catus and Bacteroides stercoris were more and less abundant in CKD, respectively, at false discovery rate corrected P = .02. CONCLUSIONS: We identified candidate taxa in the gut microbiota associated with CKD. High ICC in individuals with modest seasonal impacts implies that follow-up studies may use less frequent sampling.

Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension: SECONDARY OUTCOMES FROM THE TRIUMPH RANDOMIZED CLINICAL TRIAL.

PURPOSE: In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator. METHODS: One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale. RESULTS: Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA: 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss ( B =-0.17, P = .004) and improved oxygen uptake ( B =-0.12, P = .044) were associated with improved psychological functioning. CONCLUSION: Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.

Self-Perceived Barriers and Facilitators to Dietary Approaches to Stop Hypertension Diet Adherence Among Black Americans With Chronic Kidney Disease: A Qualitative Study.

OBJECTIVE: The Dietary Approaches to Stop Hypertension (DASH) eating plan improves hypertension in Black individuals and is associated with favorable chronic kidney disease (CKD) outcomes. Yet, adherence to DASH is low among US adults in general, particularly among Black Americans. We assessed perceptions about DASH, its cultural compatibility, and barriers and facilitators to DASH adherence in Black adults with CKD. DESIGN AND METHODS: We conducted focus groups and semistructured individual interviews involving 22 Black men and women with CKD Stages 3-4 from outpatient clinics at a US academic medical center. Transcripts of audio-recorded interviews were analyzed using thematic analysis. RESULTS: Among participants (2 focus groups [N = 8 and 5] and 9 individual interviews), 13 (59%) had CKD Stage 3, 13 (59%) were female, the median age was 61 years, and 19 (90%) had hypertension. After receiving information about DASH, participants perceived it as culturally compatible based on 3 emergent themes: (1) Black individuals already eat DASH-recommended foods ("Blacks eat pretty much like this"), (2) traditional recipes (e.g., southern or soul food) can be modified into healthy versions ("you can come up with decent substitutes to make it just as good"), and ( 3) diet is not uniform among Black individuals ("I can't say that I eat traditional"). Perceived barriers to DASH adherence included unfamiliarity with serving sizes, poor cooking skills, unsupportive household members, and high cost of healthy food. Eleven (52%) reported after paying monthly bills that they "rarely" or "never" had leftover money to purchase healthy food. Perceived facilitators included having local access to healthy food, living alone or with supportive household members, and having willpower and internal/external motivation for change. CONCLUSIONS: Black adults with CKD viewed DASH as a healthy, culturally compatible diet. Recognizing that diet in Black adults is not uniform, interventions should emphasize person-centered, rather than stereotypically culture-centered, approaches to DASH adherence.

Psychosocial determinants of cardiovascular events among black Americans with chronic kidney disease or associated risk factors in the Jackson heart study.

BACKGROUND: Individuals with chronic kidney disease (CKD), hypertension (HTN), or diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD). The extent to which psychosocial factors are associated with increased CVD risk within these individuals is unclear. Black individuals experience a high degree of psychosocial stressors due to socioeconomic factors, environment, racism, and discrimination. We examined the association between psychosocial factors and risk of CVD events among Black men and women with CKD and CKD risk factors in the Jackson Heart Study. METHODS AND RESULTS: We identified 1919 participants with prevalent CKD or CKD risk factors at baseline. We used rotated principal component analysis - a form of unsupervised machine learning that may identify constructs not intuitively identified by a person - to describe five groups of psychosocial components (including negative moods, religiosity, discrimination, negative outlooks, and negative coping resources) based on a battery of questionnaires. Multiple imputation by chained equation (MICE) was used to impute missing covariate data. Cox models were used to quantify the association between psychosocial components and incident CVD, defined as a fatal coronary heart disease event, myocardial infarction, cardiac procedure (angiography or revascularization procedure), or stroke. Of the 929 participants in the analysis, 67% were female, 28% were current/former smokers with mean age of 56 years and mean BMI of 33 kg/m2. Over a median follow-up of 8 years, 6% had an incident CVD event. In multivariable models, each standard deviation (SD) increase in the religiosity component was associated with an increased hazard for CVD event (hazard ratio [HR] = 1.52, 95% CI: 1.09-2.13). CONCLUSIONS: Religiosity was associated with CVD among participants with prevalent CKD or CKD risk factors. Studies to better understand the mechanisms of this relationship are needed.

Retrospective cohort study of changes in estimated glomerular filtration rate for patients prescribed a low carb diet.

PURPOSE OF REVIEW: Obesity and diabetes contribute to chronic kidney disease (CKD) and accelerate the loss of kidney function. Low carbohydrate diets (LCDs) are associated with weight loss and improved diabetes control. Compared to the typical Western diet, LCDs contain more protein, so individuals with CKD are not included in studies of LCDs. Therefore, there are no studies of LCDs for weight loss and their effects on kidney function. RECENT FINDINGS: Obesity, hyperglycemia, and hyperinsulinemia can be detrimental to kidney function. LCDs may improve kidney function in patients with obesity and diabetes because they are associated with weight loss, improve blood sugar control, and decrease endogenous insulin production and exogenous insulin requirements. SUMMARY: In this study, for patients with mildly reduced and moderately to severely reduced kidney function who were prescribed an LCD, their estimated glomerular filtration rate (eGFR) was either unchanged or improved. For those with normal or elevated eGFR, their kidney function was slightly decreased. For those without diabetes, greater weight loss was associated with improved eGFR. Future studies should prospectively measure low carbohydrate dietary adherence and physical activity and directly measure changes in GFR and albuminuria for participants with CKD before and during that diet.

The Nourish Protocol: A digital health randomized controlled trial to promote the DASH eating pattern among adults with hypertension.

INTRODUCTION: Over 100 million adults in the United States have hypertension. The DASH (Dietary Approaches to Stop Hypertension) eating pattern is an evidence-based first-line treatment option for hypertension; however, adherence to the DASH eating pattern at a population level remains low. To address this gap, we will implement Nourish, a randomized controlled efficacy trial that will leverage a commercially-available smartphone application and evidence-based behavior change principles to improve adherence to the DASH eating pattern among adults with hypertension. METHODS: The Nourish trial is a two-arm, 12-month randomized control trial that will enroll adults (N = 300) with hypertension, defined as a systolic blood pressure of 120-159 mmHg; a diastolic blood pressure of 80-99 mmHg; and/or adults on blood pressure-lowering medication. Nourish will test the efficacy of a digital health intervention, as compared to the attention control arm, on DASH eating pattern adherence and blood pressure. Intervention components will include skills training, self-monitoring, personalized feedback, and responsive coaching. The primary outcome of the trial is 6-month changes in adherence to the DASH eating pattern, as measured by 24-h dietary recalls. DISCUSSION: Millions of Americans remain in need of effective behavioral interventions to manage and improve their hypertension and its adverse consequences. The ubiquity of smartphones offers a promising approach to disseminate the DASH eating pattern. By leveraging these widely used smartphone applications, combined with evidence-based behavior change principles and the DASH eating plan, Nourish will demonstrate the effectiveness of a digital health intervention to improve DASH adherence, and ultimately, to reduce blood pressure. Trial Number: NCT03875.

Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study.

We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.

Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study.

RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. STUDY DESIGN: Randomized order, cross-over study with controlled feeding. SETTING & PARTICIPANTS: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. INTERVENTION: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. OUTCOMES: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. RESULTS: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. LIMITATIONS: Small sample size and short feeding duration. CONCLUSIONS: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02427594.

Association of functional and structural social support with chronic kidney disease among African Americans: the Jackson Heart Study.

BACKGROUND: There is limited evidence on the relationship between social support and renal outcomes in African Americans. We sought to determine the association of social support with prevalent chronic kidney disease (CKD) and kidney function decline in an African American cohort. We also examined whether age modifies the association between social support and kidney function decline. METHODS: We identified Jackson Heart Study (JHS) participants with baseline (Exam in 2000-2004) functional and structural social support data via the Interpersonal Support Evaluation List (ISEL) and social network size questions, respectively. With ISEL as our primary exposure variable, we performed multivariable regression models to evaluate the association between social support and prevalent CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin-creatinine ratio (ACR) ≥30 mg/g], eGFR decline, and rapid renal function decline (RRFD) (> 30% decrease in eGFR over approximately 10 years). All models were adjusted for baseline sociodemographics, diabetes, hypertension, smoking status, and body mass index; models for eGFR decline and RRFD were additionally adjusted for eGFR and ACR. In models for eGFR decline, we assessed for interaction between age and social support. For secondary analyses, we replaced ISEL with its individual domains (appraisal, belonging, self-esteem, and tangible) and social network size in separate models as exposure variables. RESULTS: Of 5301 JHS participants, 4015 (76%) completed the ISEL at baseline. 843 (21%) had low functional social support (ISEL score < 32). Participants with low (vs. higher) functional social support were more likely to have lower income (47% vs. 28%), be current or former tobacco users (39% vs. 30%), have diabetes (25% vs. 21%) or CKD (14% vs. 12%). After multivariable adjustment, neither ISEL or social network size were independently associated with prevalent CKD, eGFR decline, or RRFD. Of the ISEL domains, only higher self-esteem was associated with lower odds of prevalent CKD [OR 0.94 (95% CI 0.89-0.99)]. The associations between social support measures and eGFR decline were not modified by age. CONCLUSIONS: In this African-American cohort, social support was not associated with prevalent CKD or kidney function decline. Further inquiry of self-esteem's role in CKD self-management and renal outcomes is warranted.

DASH Diet and Blood Pressure Among Black Americans With and Without CKD: The Jackson Heart Study.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) more effectively in blacks compared to other US racial subgroups. Considering chronic kidney disease (CKD) raises BP through complex mechanisms, DASH may affect BP differently among blacks with and without CKD. We compared the association of DASH accordance to BP and prevalent hypertension among blacks with and without CKD. METHODS: Our study involved 3,135 black Americans enrolled in the Jackson Heart Study (2000-2004) with diet and office BP data. Using linear models adjusted for demographics, health behaviors, and clinical factors, we determined the association of a modified DASH score (excluding sodium intake, ranging from 0 to 8 with increasing DASH accordance) with BP. We performed tests for interaction between DASH score and CKD status. RESULTS: Among participants (mean age: 55 years; hypertension: 60%; CKD: 19%), the median DASH score was similar among participants with and without CKD (1.0 [interquartile range (IQR): 0.5-2] and 1.0 [IQR: 0.5-1.5]). CKD status modified the association of the DASH score with systolic BP (SBP) and diastolic BP (DBP; P interactions were 0.06 and <0.01). Among participants without CKD, SBP and DBP were not associated with the DASH score (-0.4 [95% confidence interval: -1.0, 0.1] mm Hg and -0.1 [-0.4, 0.2] mm Hg per one unit higher DASH score). Among participants with CKD, one unit higher DASH score was associated with lower SBP by 1.6 (0.5, 2.6) mm Hg and lower DBP by 0.9 (0.3, 1.5) mm Hg. CONCLUSIONS: Despite low DASH scores overall, better DASH accordance was associated with lower BP among Black Americans with CKD.

Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial.

AIMS: The randomized sham-controlled SPYRAL HTN-OFF MED trial demonstrated that renal denervation (RDN) using a multi-electrode catheter lowers ambulatory blood pressure (BP) in non-medicated hypertensive patients. The current report describes the effects of RDN on heart rate (HR) in this population. METHODS AND RESULTS: Patients were enrolled with an office systolic BP (SBP) of ≥150 mmHg and <180 mmHg, office diastolic BP (DBP) of ≥90 mmHg, and a mean ambulatory SBP of ≥140 mmHg and <170 mmHg. Patients were drug naïve or removed from their anti-hypertensive medications. Eighty patients were randomized 1:1 to RDN or sham procedure. This post hoc analysis examines the effect at 3 months of RDN on HR and of high baseline 24-h HR on BP and HR changes. There was a significant reduction in 24-h HR at 3 months for the RDN group (-2.5 b.p.m.) compared with sham (-0.2 b.p.m.), P = 0.003 (analysis of covariance). Mean baseline-adjusted treatment differences were significantly different between groups at 3 months for average morning HR (-4.4 b.p.m., P = 0.046) and minimum morning HR (-3.0 b.p.m., P = 0.026). RDN patients with baseline 24-h HR above the median (73.5 b.p.m.) had significant reductions in average ambulatory SBP (-10.7 mmHg difference, P = 0.001) and DBP (-7.5 mmHg, P < 0.001), whereas BP changes in RDN patients with below-median HRs were not significant. CONCLUSION: Average and minimum morning HR were significantly reduced at 3 months for RDN compared with sham patients. A baseline 24-h HR above the median predicted greater BP reductions and may allow physicians to select patients likely to respond to the procedure.

Dietary Phosphorus and Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

BACKGROUND: Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns. METHODS: Our study included 973 African American adults enrolled in the Jackson Heart Study (2000-2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension. RESULTS: There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping. CONCLUSIONS: These data do not support a role for higher phosphorus intake and higher BP in African Americans.

Ambulatory blood pressure in the dash diet trial: Effects of race and albuminuria.

We evaluated whether low-grade albuminuria or black race modulates ambulatory blood pressure (BP) or nocturnal BP response to the DASH diet. Among 202 adults enrolled in the DASH multicenter trial who were fed the DASH or control diet for 8 weeks, reductions in 24-hour daytime and nighttime SBP and DBP were significantly larger for DASH compared to control. Median changes in nocturnal BP dipping were not significant. Compared to urine albumin excretion of <7 mg/d, ≥7 mg/d was associated with larger significant median reductions in 24-hour SBP (-7.3 vs -3.1 mm Hg), all measures of DBP (24-hour: -5.9 vs -1.8 mm Hg; daytime: -9.9 vs -4.0 mm Hg; nighttime -9.0 vs -2.0 mm Hg), and with increased nocturnal SBP dipping (2.3% vs -0.5%). Black race was associated with larger median reduction in 24-hour SBP only (-5.5 vs -2.4 mm Hg). This analysis suggests greater effect of DASH on ambulatory BP in the presence of low-grade albuminuria.

Nondepressive Psychosocial Factors and CKD Outcomes in Black Americans.

BACKGROUND AND OBJECTIVES: Established risk factors for CKD do not fully account for risk of CKD in black Americans. We studied the association of nondepressive psychosocial factors with risk of CKD in the Jackson Heart Study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used principal component analysis to identify underlying constructs from 12 psychosocial baseline variables (perceived daily, lifetime, and burden of lifetime discrimination; stress; anger in; anger out; hostility; pessimism; John Henryism; spirituality; perceived social status; and social support). Using multivariable models adjusted for demographics and comorbidity, we examined the association of psychosocial variables with baseline CKD prevalence, eGFR decline, and incident CKD during follow-up. RESULTS: Of 3390 (64%) Jackson Heart Study participants with the required data, 656 (19%) had prevalent CKD. Those with CKD (versus no CKD) had lower perceived daily (mean [SD] score =7.6 [8.5] versus 9.7 [9.0]) and lifetime discrimination (2.5 [2.0] versus 3.1 [2.2]), lower perceived stress (4.2 [4.0] versus 5.2 [4.4]), higher hostility (12.1 [5.2] versus 11.5 [4.8]), higher John Henryism (30.0 [4.8] versus 29.7 [4.4]), and higher pessimism (2.3 [2.2] versus 2.0 [2.1]; all P<0.05). Principal component analysis identified three factors from the 12 psychosocial variables: factor 1, life stressors (perceived discrimination, stress); factor 2, moods (anger, hostility); and, factor 3, coping strategies (John Henryism, spirituality, social status, social support). After adjustments, factor 1 (life stressors) was negatively associated with prevalent CKD at baseline among women only: odds ratio, 0.76 (95% confidence interval, 0.65 to 0.89). After a median follow-up of 8 years, identified psychosocial factors were not significantly associated with eGFR decline (life stressors: ß=0.08; 95% confidence interval, -0.02 to 0.17; moods: ß=0.03; 95% confidence interval, -0.06 to 0.13; coping: ß=-0.02; 95% confidence interval, -0.12 to 0.08) or incident CKD (life stressors: odds ratio, 1.07; 95% confidence interval, 0.88 to 1.29; moods: odds ratio, 1.02; 95% confidence interval, 0.84 to 1.24; coping: odds ratio, 0.91; 95% confidence interval, 0.75 to 1.11). CONCLUSIONS: Greater life stressors were associated with lower prevalence of CKD at baseline in the Jackson Heart Study. However, psychosocial factors were not associated with risk of CKD over a median follow-up of 8 years. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_01_03_CJASNPodcast_18_2_L.mp3.

Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

Background: African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods: We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study. We quantified obesity as body mass index (BMI), sex-normalized waist circumference and visceral adipose volume measured by abdominal computed tomography at an interim study visit. Interactions were hypothesized with (i) metabolic risk factors (dietary quality and physical activity, both quantified by concordance with American Heart Association guidelines) and (ii) factors exacerbating or mitigating hyperfiltration (dietary protein intake, APOL1 risk status and use of renin-angiotensin system blocking medications). Using multivariable regression, we evaluated associations between obesity measures and incident CKD over the follow-up period, as well as interactions with metabolic and hyperfiltration factors. Results: Assessed after a median of 8 years (range 6-11 years), baseline BMI and waist circumference were not associated with incident CKD. Higher visceral adipose volume was independently associated with incident CKD (P = 0.008) in a nonlinear fashion, but this effect was limited to those with lower dietary quality (P = 0.001; P-interaction = 0.04). In additional interaction models, higher waist circumference was associated with greater risk of incident CKD among those with the low-risk APOL1 genotype (P = 0.04) but not those with a high-risk genotype (P-interaction = 0.02). Other proposed factors did not modify obesity-CKD associations. Conclusions. Higher risks associated with metabolically active visceral adipose volume and interactions with dietary quality suggest that metabolic factors may be key determinants of obesity-associated CKD risk. Interactions between obesity and APOL1 genotype should be considered in studies of African Americans.

Association between normal or mildly reduced kidney function, cardiovascular risk and biomarkers for atherosclerosis: results from the ENCORE trial.

BACKGROUND: Moderate-to-severe kidney dysfunction is associated with atherosclerotic cardiovascular disease (ASCVD). Gradations of normal or mildly reduced kidney function may also associate with ASCVD risk. METHODS: We conducted a secondary analysis using baseline data from the Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE) trial. Participants were sedentary, overweight and obese adults with unmedicated pre-hypertension or Stage I hypertension and an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. The Pooled Cohorts Equations were used to estimate a 10-year risk for first ASCVD event. Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured to assess subclinical atherosclerosis and vascular endothelial function, respectively. Using linear regression, we examined the association between eGFR and ASCVD risk, IMT and FMD. RESULTS: Participants (N = 139) were predominantly women (65%), white (60%), with a mean age of 52.0 ± 9.6 years and mean eGFR of 89.1 ± 15.0 mL/min/1.73 m2. Lower eGFR of 15 mL/min/1.73 m2 was associated with higher ASCVD risk [b = -2.7% (95% confidence interval: -3.7, -1.8%), P < 0.001], higher IMT [b = 0.05 mm (0.03, 0.08 mm), P < 0.001] and lower FMD [b = -0.87% (-1.64, -0.11%), P = 0.026]. Compared with eGFR ≥90 mL/min/1.73 m2, those with eGFR 60-89 mL/min/1.73 m2 had higher mean ASCVD risk (7.6% versus 2.7%; P < 0.001), greater mean IMT (0.74 mm versus 0.66 mm; P < 0.001) and lower mean FMD (2.0% versus 3.7%; P = 0.026). After controlling for CVD risk factors, the association between eGFR and IMT remained significant (P < 0.001), and eGFR and FMD trended toward significance (P = 0.08). CONCLUSIONS: Among overweight and obese adults with unmedicated high blood pressure and eGFR ≥60 mL/min/1.73 m2, lower eGFR is associated with a greater 10-year risk for first ASCVD event, higher IMT and relatively impaired FMD.

In the Wake of Systolic Blood Pressure Intervention Trial: New Targets for Improving Hypertension Management in Chronic Kidney Disease?

Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter randomized controlled trial showing the significant benefit of intensive reduction of blood pressure to a target of 120 mm Hg in individuals with hypertension and elevated cardiovascular risk. Because SPRINT includes the largest cohort of adults with chronic kidney disease (CKD) to be prospectively studied in a hypertension intervention trial, it has particular relevance to the field of nephrology. Here, we review the findings of SPRINT and assess their potential impact on guidelines for treatment of hypertension in patients with CKD. We believe that the data from SPRINT will support a recommendation for lowering blood pressure targets to 120 mm Hg in a substantial segment of adults with CKD.

Short-term effects of the DASH diet in adults with moderate chronic kidney disease: a pilot feeding study.

BACKGROUND: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) for adults with normal kidney function, evidence is lacking regarding its safety and efficacy in chronic kidney disease (CKD). We aimed to test the effects of the DASH diet on serum electrolytes and BP in adults with moderate CKD. METHODS: In a prospective before-after feeding study, 11 adults with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m(2) and medication-treated hypertension were provided a reduced-sodium, run-in diet for 1 week followed by a reduced-sodium, DASH diet for 2 weeks. Changes in serum electrolytes and BP were compared pre-post DASH. RESULTS: Eleven participants underwent feeding; 1 completed 1 week and 10 completed 2 weeks of DASH. Compared with baseline, DASH modestly increased serum potassium at 1 week (mean ± standard deviation, +0.28 ± 0.4 mg/dL; P = 0.043) but had no significant effect on potassium at 2 weeks (+0.15 ± 0.28 mg/dL; P = 0.13). Serum bicarbonate was reduced (-2.5 ± 3.0 mg/dL; P = 0.03) at 2 weeks. Neither incident hyperkalemia nor new onset metabolic acidosis was observed. Clinic BP and mean 24-h ambulatory BP was unchanged. DASH significantly reduced mean nighttime BP (-5.3 ± 5.8 mmHg; P = 0.018), and enhanced percent declines in both nocturnal systolic BP (-2.1% to -5.1%; P = 0.004) and diastolic BP (-3.7% to -10.0%; P = 0.008). CONCLUSIONS: These pilot data suggest that a reduced-sodium DASH dietary pattern does not cause acute metabolic events in adults with moderate CKD and may improve nocturnal BP. Definitive studies are needed to determine long-term effects of DASH in CKD.