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.

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.

A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2).

PURPOSE: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer. EXPERIMENTAL DESIGN: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m2 and PSADT 3 to 36 months. The LCD arm was instructed to eat [Formula: see text]20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet. RESULTS: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-seven LCD and 18 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (-117 vs. 8 g, P < 0.001) and lost weight (-12.1 vs. -0.50 kg, P < 0.001). The LCD arm reduced HDL, triglycerides, and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (21 months) and control (15 months, P = 0.316) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, P = 0.021) arms. Adverse events were few, usually mild, and returned to baseline by 6 months. CONCLUSIONS: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.

A lifestyle intervention of weight loss via a low-carbohydrate diet plus walking to reduce metabolic disturbances caused by androgen deprivation therapy among prostate cancer patients: carbohydrate and prostate study 1 (CAPS1) randomized controlled trial.

PURPOSE: The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances. MATERIALS AND METHODS: This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests. RESULTS: At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control (p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p<0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p<0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count (p = 0.025), reduced fat mass (p = 0.002), lean mass (p = 0.036), and percent body fat (p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size. CONCLUSIONS: In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.

The Association Between Engagement and Weight Loss Through Personal Coaching and Cell Phone Interventions in Young Adults: Randomized Controlled Trial.

BACKGROUND: Understanding how engagement in mobile health (mHealth) weight loss interventions relates to weight change may help develop effective intervention strategies. OBJECTIVE: This study aims to examine the (1) patterns of participant engagement overall and with key intervention components within each intervention arm in the Cell Phone Intervention For You (CITY) trial; (2) associations of engagement with weight change; and (3) participant characteristics related to engagement. METHODS: The CITY trial tested two 24-month weight loss interventions. One was delivered with a smartphone app (cell phone) containing 24 components (weight tracking, etc) and included prompting by the app in predetermined frequency and forms. The other was delivered by a coach via monthly calls (personal coaching) supplemented with limited app components (18 overall) and without any prompting by the app. Engagement was assessed by calculating the percentage of days each app component was used and the frequency of use. Engagement was also examined across 4 weight change categories: gained (≥2%), stable (±2%), mild loss (≥2% to <5%), and greater loss (≥5%). RESULTS: Data from 122 cell phone and 120 personal coaching participants were analyzed. Use of the app was the highest during month 1 for both arms; thereafter, use dropped substantially and continuously until the study end. During the first 6 months, the mean percentage of days that any app component was used was higher for the cell phone arm (74.2%, SD 20.1) than for the personal coaching arm (48.9%, SD 22.4). The cell phone arm used the apps an average of 5.3 times/day (SD 3.1), whereas the personal coaching participants used them 1.7 times/day (SD 1.2). Similarly, the former self-weighed more than the latter (57.1% days, SD 23.7 vs 32.9% days, SD 23.3). Furthermore, the percentage of days any app component was used, number of app uses per day, and percentage of days self-weighed all showed significant differences across the 4 weight categories for both arms. Pearson correlation showed a negative association between weight change and the percentage of days any app component was used (cell phone: r=-.213; personal coaching: r=-.319), number of apps use per day (cell phone: r=-.264; personal coaching: r=-.308), and percentage of days self-weighed (cell phone: r=-.297; personal coaching: r=-.354). None of the characteristics examined, including age, gender, race, education, income, energy expenditure, diet quality, and hypertension status, appeared to be related to engagement. CONCLUSIONS: Engagement in CITY intervention was associated with weight loss during the first 6 months. Nevertheless, engagement dropped substantially early on for most intervention components. Prompting may be helpful initially. More flexible and less intrusive prompting strategies may be needed during different stages of an intervention to increase or sustain engagement. Future studies should explore the motivations for engagement and nonengagement to determine meaningful levels of engagement required for effective intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01092364; https://clinicaltrials.gov/ct2/show/NCT01092364 (Archived by WebCite at http://www.webcitation.org/72V8A4e5X).

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.