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

Tyson, Crystal C.; Luciano, Alison; Modliszewski, Jennifer L.; Corcoran, David L.; Bain, James R.; Muehlbauer, Michael J.; Pourafshar, Shirin; Allen, Jenifer; Bowman, Cassandra; Gung, Joseph; Asplin, John R.; Pendergast, Jane; Svetkey, Laura P.; Lin, Pao‐Hwa; Scialla, Julia J.

doi:10.1053/j.ajkd.2020.10.015

Cited by 16 publications

(7 citation statements)

References 27 publications

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“…To characterize the metabolic impacts of the DASH diet, we performed untargeted gas chromatography/mass spectrometry (GC/MS) on stored non-missing fasting plasma (n = 56 out of 60 time points were available) and 24-h urine, diluted in pure water to achieve constant creatinine concentration across samples (n = 40 out of 60 time points were available). Detailed GC/MS methods are published elsewhere [ 8 ]. All metabolites are quantified as the log 2 peak areas.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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“…, a daily fruit offering, salad bar, or off-menu eating that occurred away from the center). To specifically evaluate how features of the Weight Loss diet record may have affected per-taxon detection accuracy, we examined a stricter intervention cohort consuming a Western-style diet that was provisioned food from four recurring daily menus, with uneaten items returned and detailed daily food logs captured additional items consumed (“Controlled Feeding,” Table 1 , n = 28 samples from 14 individuals) ( 23 ). Across foods in common between the Weight Loss and Controlled Feeding cohorts ( n = 42), detection errors were significantly correlated for false negative rate (Spearman ρ = 0.63, P = 0.0003; SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

Diversity of plant DNA in stool is linked to dietary quality, age, and household income

Petrone

Aqeel

Jiang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast trnL -P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.40 to 0.63). In adolescents unable to collect validated dietary survey data, trnL metabarcoding detected 111 plant taxa, with 86 consumed by more than one individual and four (wheat, chocolate, corn, and potato family) consumed by >70% of individuals. Adolescent pMR was associated with age and household income, replicating prior epidemiologic findings. Overall, trnL metabarcoding promises an objective and accurate measure of the number and types of plants consumed that is applicable to diverse human populations.

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“…Alternative explanations such as a long-term improvement in the kidney's ability to excrete acid with 4–8 weeks of veverimer treatment during the run-in period are unlikely, given that veverimer is not absorbed and the short offset of effect observed in earlier studies. 13–15 Similarly, a long-term change in diet due to dietary counseling in the placebo group is also an unlikely explanation given that dietary counseling alone, without the provision of food, has been shown to be ineffective for the treatment of metabolic acidosis. 16 As with earlier trials, the mean achieved serum bicarbonate in the veverimer group was approximately 22 mEq/L, but the placebo subtracted treatment effect in earlier trials of 3–5 mEq/L was not achieved in this trial due to a larger than expected sustained increase in the serum bicarbonate levels in the placebo group.…”

Section: Discussionmentioning

confidence: 99%

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis

Tangri,

Mathur,

Bushinsky

et al. 2024

JASN

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Background: Metabolic acidosis is common in chronic kidney disease (CKD), but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. Methods: In a Phase 3, double-blind, placebo-controlled trial, patients with CKD (estimated glomerular filtration rate [eGFR] of 20-40 mL/min/1.73 m2) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite endpoint of CKD progression, defined as the development of end-stage kidney disease (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of >40% from baseline, or death due to kidney failure. Results: The mean (±SD) baseline eGFR was 29.2 ± 6.3 mL/min/1.73 m2 and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4 ± 2.0 mEq/L after the active-treatment run-in. Following randomized withdrawal, the mean serum bicarbonate was 22.0 ± 3.0 mEq/L and 20.9 ± 3.3 mEq/L in the veverimer and placebo groups at Month 3 and this ∼ 1mEq/L difference remained stable for the first 24 months. A primary endpoint event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95 % CI, 0.8 to 1.2; P=0.90). Serious and overall adverse event incidence did not differ between the groups. Conclusions: Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. (Funded by Tricida, Inc.; VALOR-CKD ClinicalTrials.gov number, NCT037102).

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

Cited by 16 publications

References 27 publications

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

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

Diversity of plant DNA in stool is linked to dietary quality, age, and household income

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis

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