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Journal of Dairy Science Feb 2021The objective of this experiment was to determine the effects of altering the dietary cation-anion difference (DCAD) fed for the last 21 or 42 d of gestation on glucose...
The objective of this experiment was to determine the effects of altering the dietary cation-anion difference (DCAD) fed for the last 21 or 42 d of gestation on glucose metabolism and tissue insulin responsiveness. Ninety parous Holstein cows at 232 d of gestation were assigned randomly to dietary treatments with 2 levels of DCAD (-70 or -180 mEq/kg) fed for 2 durations (short: the last 21 d of gestation; long: the last 42 d of gestation). For the short treatments, a diet with +110 mEq/kg was fed from 232 to 254 d of gestation. Intravenous glucose tolerance tests (IVGTT) were performed at either 250 or 270 d of gestation by infusing 0.25 g of dextrose/kg of body weight within 1 min. The following day, cows underwent an insulin challenge (IC) and received 0.1 IU of insulin/kg of body weight intravenously. Blood was sampled at min -15, -5, and 0 to establish a baseline and from 5 to 180 min relative to infusions; plasma concentrations of glucose, insulin, and fatty acids were determined, and the respective areas under the curves (AUC) were calculated. Liver was sampled after the IVGTT, and adipose tissue was sampled after the IVGTT and IC for quantification of mRNA expression and protein abundance. Reducing the DCAD altered acid-base balance compatible with a compensated metabolic acidosis. At 250 d, reducing the DCAD increased the AUC for glucose and reduced that of insulin following the IVGTT, whereas during the IC, clearance rate decreased and time to half-life of insulin increased with reducing DCAD, resulting in a tendency to a larger AUC for fatty acids. At 270 d, quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index were smaller in cows fed the acidogenic diets for the last 42 d of gestation compared with the last 21 d of gestation, thereby suggesting reduced insulin sensitivity. In addition, cows fed for the long duration tended to have greater AUC for glucose but smaller AUC for insulin following an IVGTT than those fed for the short duration, thereby suggesting reduced insulin release and glucose disposal. Treatments did not affect hepatic mRNA expression of G6PC, PCK1, PCK2, and PC or adipose tissue mRNA expression of ATGL, ACC, B2AR, HSL, and PLIN1. On the other hand, for proteins, reducing the DCAD linearly reduced abundance of rabbit anti-mouse protein kinase B (AKT) and tended to reduce rabbit anti-human phosphorylated (Ser-9) glycogen synthase kinase-3 β (pGSK) and the pGSK:rabbit anti-human glycogen synthase kinase-3 β (GSK) ratio in hepatic tissue, whereas a linear increase in rabbit anti-human hormone-sensitive lipase (HSL) and rabbit anti-mouse phosphorylated (Ser-660) hormone-sensitive lipase (pHSL) in adipose tissue was observed after the IVGTT at 250 d. Moreover, reducing the DCAD resulted in a linear reduction of AKT and tended to reduce rabbit anti-human acetyl-CoA carboxylase (ACC) but increased pHSL linearly in adipose tissue after an IC at 250 d. Cows fed acidogenic diets for a short duration tended to have less pHSL in adipose tissue than those fed for a long duration after an IVGTT at 270 d. Associations were observed between blood pH and mRNA and protein abundance in hepatic and adipose tissues. Diet-induced metabolic acidosis altered insulin release and insulin signaling, resulting in a shift in adipose tissue metabolism that would favor lipolysis over lipogenesis.
Topics: Acidosis; Adipose Tissue; Animal Feed; Animals; Blood Glucose; Cattle; Cattle Diseases; Dairying; Diet; Energy Metabolism; Female; Gestational Age; Glucose Tolerance Test; Insulin; Lipogenesis; Lipolysis; Liver; Pregnancy; Pregnancy Complications
PubMed: 33309345
DOI: 10.3168/jds.2020-18787 -
BMC Nephrology May 2021Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of... (Observational Study)
Observational Study
Metabolic acidosis is associated with increased risk of adverse kidney outcomes and mortality in patients with non-dialysis dependent chronic kidney disease: an observational cohort study.
BACKGROUND
Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort.
METHODS
In this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum's de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years.
RESULTS
A total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922-0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866-0.879; P < 0.001).
CONCLUSIONS
In this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).
Topics: Acidosis; Aged; Bicarbonates; Disease Progression; Female; Glomerular Filtration Rate; Humans; Incidence; Longitudinal Studies; Male; Renal Insufficiency, Chronic; Renal Replacement Therapy; Retrospective Studies; Risk Factors
PubMed: 34011303
DOI: 10.1186/s12882-021-02385-z -
Pflugers Archiv : European Journal of... Apr 2024Maintaining an appropriate acid-base equilibrium is crucial for human health. A primary influencer of this equilibrium is diet, as foods are metabolized into... (Review)
Review
Maintaining an appropriate acid-base equilibrium is crucial for human health. A primary influencer of this equilibrium is diet, as foods are metabolized into non-volatile acids or bases. Dietary acid load (DAL) is a measure of the acid load derived from diet, taking into account both the potential renal acid load (PRAL) from food components like protein, potassium, phosphorus, calcium, and magnesium, and the organic acids from foods, which are metabolized to bicarbonate and thus have an alkalinizing effect. Current Western diets are characterized by a high DAL, due to large amounts of animal protein and processed foods. A chronic low-grade metabolic acidosis can occur following a Western diet and is associated with increased morbidity and mortality. Nutritional advice focusing on DAL, rather than macronutrients, is gaining rapid attention as it provides a more holistic approach to managing health. However, current evidence for the role of DAL is mainly associative, and underlying mechanisms are poorly understood. This review focusses on the role of DAL in multiple conditions such as obesity, cardiovascular health, impaired kidney function, and cancer.
Topics: Animals; Humans; Diet; Acid-Base Equilibrium; Kidney; Acidosis; Obesity
PubMed: 38282081
DOI: 10.1007/s00424-024-02910-7 -
Journal of the American Society of... Mar 2020Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In...
Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.
Topics: Acid-Base Equilibrium; Acidosis; Adaptation, Physiological; Aldosterone; Angiotensin II; Biomarkers; Disease Progression; Endothelin-1; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 31988269
DOI: 10.1681/ASN.2019070677 -
Bioscience Reports Mar 2023Severe coronavirus disease 2019 (COVID-19) infection can lead to extensive lung infiltrate, a significant increase in the respiratory rate, and respiratory failure,...
Severe coronavirus disease 2019 (COVID-19) infection can lead to extensive lung infiltrate, a significant increase in the respiratory rate, and respiratory failure, which can affect the acid-base balance. No research in the Middle East has previously examined acid-base imbalance in COVID-19 patients. The present study aimed to describe the acid-base imbalance in hospitalized COVID-19 patients, determine its causes, and assess its impact on mortality in a Jordanian hospital. The study divided patients into 11 groups based on arterial blood gas data. Patients in normal group were defined as having a pH of 7.35-7.45, PaCO2 of 35-45 mmHg, and HCO3- of 21-27 mEq/L. Other patients were divided into 10 additional groups: mixed acidosis and alkalosis, respiratory and metabolic acidosis with or without compensation, and respiratory and metabolic alkalosis with or without compensation. This is the first study to categorize patients in this way. The results showed that acid-base imbalance was a significant risk factor for mortality (P<0.0001). Mixed acidosis nearly quadruples the risk of death when compared with those with normal levels (OR = 3.61, P=0.05). Furthermore, the risk of death was twice as high (OR = 2) for metabolic acidosis with respiratory compensation (P=0.002), respiratory alkalosis with metabolic compensation (P=0.002), or respiratory acidosis with no compensation (P=0.002). In conclusion, acid-base abnormalities, particularly mixed metabolic and respiratory acidosis, were associated with increased mortality in hospitalized COVID-19 patients. Clinicians should be aware of the significance of these abnormalities and address their underlying causes.
Topics: Humans; Acidosis, Respiratory; COVID-19; Acid-Base Imbalance; Alkalosis; Acidosis; Risk Factors
PubMed: 36876487
DOI: 10.1042/BSR20222362 -
Clinical Journal of the American... Jul 2019Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to evaluate the benefits and risks of metabolic acidosis treatment with oral alkali supplementation or a reduction of dietary acid intake in those with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
MEDLINE, Embase, and Cochrane CENTRAL were searched for relevant trials in patients with stage 3-5 CKD and metabolic acidosis (<22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L). Data were pooled in a meta-analysis with results expressed as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs), using a random effects model. Study quality and strength of evidence were assessed using Cochrane risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria.
RESULTS
Fourteen clinical trials were included (=1394 participants). Treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake increased serum bicarbonate levels (14 studies, 1378 patients, mean difference 3.33 mEq/L, 95% CI, 2.37 to 4.29) and resulted in a slower decline in eGFR (13 studies, 1329 patients, mean difference -3.28 ml/min per 1.73 m, 95% CI, -4.42 to -2.14; moderate certainty) and a reduction in urinary albumin excretion (very-low certainty), along with a reduction in the risk of progression to ESKD (relative risk, 0.32; 95% CI, 0.18 to 0.56; low certainty). Oral alkali supplementation was associated with worsening hypertension or the requirement for increased antihypertensive therapy (very-low certainty).
CONCLUSIONS
Low-to-moderate certainty evidence suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of ESKD in patients with CKD and metabolic acidosis.
Topics: Acidosis; Alkalies; Bicarbonates; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic
PubMed: 31196951
DOI: 10.2215/CJN.13091118 -
Jornal Brasileiro de Nefrologia 2020Metabolic acidosis is associated with the high mortality seen in hemodialysis patients. The panorama of metabolic acidosis in hemodialysis in Brazil is unclear since...
INTRODUCTION
Metabolic acidosis is associated with the high mortality seen in hemodialysis patients. The panorama of metabolic acidosis in hemodialysis in Brazil is unclear since 1996 when the analysis of bicarbonate levels was no longer a compulsory exam. We aimed to establish the prevalence of metabolic acidosis in a hemodialysis population and analyze the factors associated with low bicarbonate levels.
METHODS
A cross-sectional study was carried out to assess the prevalence of metabolic acidosis in adults undergoing regular hemodialysis from January to April 2017, in four dialysis centers from Niteroi, Rio de Janeiro, Brazil, and surroundings. For blood gas analysis, samples of 2 mL were collected in heparinized syringes before a midweek dialysis session.
RESULTS
384 patients with a mean age of 58.1 ± 15.8 years (54.5% men and 63.0%, non-white) were included. Approximately 30% had diabetes and 48%, hypertension. Nearly 88% used primary arteriovenous fistula as vascular access. The pre-dialysis mean serum tCO2 in the midweek session was 22.7 ± 3.0 mEq/L. The prevalence rate of serum bicarbonate below DOQI recommendation (22 mEq/L or higher) was 40.3%, and 6.5% had serum bicarbonate < 18 mEq/L. The dialyzer use count and the use of low-flux dialyzers were negatively associated whereas age and the standard Kt/V values were positively associated with the serum bicarbonate levels.
CONCLUSION
The findings were in agreement with global data reported in previous studies. However, because the sample was relatively small and non-representative of the Brazilian population, a more comprehensive study, addressing national data is necessary to substantiate our findings.
Topics: Acidosis; Adult; Aged; Brazil; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis
PubMed: 32353104
DOI: 10.1590/2175-8239-JBN-2019-0210 -
American Journal of Physiology. Renal... Mar 2021Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop...
Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NHCl, 7.2 mmol/220 g body wt/day to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence microscopy, and quantitative PCR (qPCR) analysis of claudins and the calcium-sensing receptor. As expected, NHCl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NHCl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19, were decreased compared with controls. However, claudin-14 protein and mRNA increased in NHCl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were up-regulated in NHCl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NHCl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are down-regulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor. This study found that the thick ascending limb of Henle's loop is involved in the mechanisms of hypercalciuria and hypermagnesiuria in metabolic acidosis. Specifically, expression of claudin-16/19 and claudin-14 was altered via up-regulation of calcium-sensing receptor in NHCl-induced metabolic acidosis. Our novel findings contribute to understanding the regulatory role of paracellular tight junction proteins in the thick ascending limb.
Topics: Acidosis; Animals; Calcium; Calcium, Dietary; Claudins; Hypercalciuria; Loop of Henle; Magnesium; Male; Rats, Sprague-Dawley; Receptors, Calcium-Sensing; Rats
PubMed: 33522409
DOI: 10.1152/ajprenal.00282.2020 -
Kidney360 Jun 2024
Randomized Controlled Trial
Topics: Humans; Hyperkalemia; Renal Insufficiency, Chronic; Acidosis; Silicates; Male
PubMed: 38622759
DOI: 10.34067/KID.0000000000000446 -
Pediatric Nephrology (Berlin, Germany) Apr 2024The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1.... (Review)
Review
The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of β-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and β-hydroxybutyrate.
Topics: Infant, Newborn; Child; Female; Humans; Hypoglycemic Agents; Diabetic Ketoacidosis; 3-Hydroxybutyric Acid; Lactation; Ketosis; Ketone Bodies
PubMed: 37584686
DOI: 10.1007/s00467-023-06115-5