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Nature Reviews. Disease Primers May 2020
Topics: Acidosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Management; Fluid Therapy; Humans; Hypoglycemic Agents; Insulin; Risk Factors
PubMed: 32409653
DOI: 10.1038/s41572-020-0180-2 -
Lancet (London, England) Feb 2023Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients.
METHODS
The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m and 89 mL/min per 1·73 m, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996.
FINDINGS
Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death.
INTERPRETATION
In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis.
FUNDING
Swiss National Science Foundation.
Topics: Adult; Humans; Male; Female; Adolescent; Sodium Bicarbonate; Bicarbonates; Switzerland; Kidney Transplantation; Single-Blind Method; Double-Blind Method; SARS-CoV-2; COVID-19; Acidosis; Treatment Outcome
PubMed: 36708734
DOI: 10.1016/S0140-6736(22)02606-X -
Archives of Iranian Medicine Nov 2019Methanol is a clear liquid with high toxicity. Methanol intoxication may result from accidental exposure, overconsumption of compounds containing methanol with suicidal...
Methanol is a clear liquid with high toxicity. Methanol intoxication may result from accidental exposure, overconsumption of compounds containing methanol with suicidal intent, or following consumption of distilled and contaminated alcoholic beverages. This report describes a case of transdermal methanol intoxication, which is a rare condition. A 58-year-old woman presented with nausea, vomiting, weakness, diplopia and dizziness. On neurological examination, she only had diplopia. On physical examination, a hyperemic lesion with clear borders was found over the right knee. The patient's recent medical history revealed that four days prior to the onset of symptoms, she had covered her knee with a methanol-soaked bandage in an attempt to alleviate her knee pain. She had a high osmolar gap as well as high anion-gap metabolic acidosis (HAGMA). Methanol intoxication was suspected due to HAGMA and high osmolar gap. Serum methanol levels were subsequently measured and found to be 37.9 mg/ dL. The patient was treated with intravenous (IV) bicarbonate, IV ethyl alcohol and hemodialysis. She was discharged with no central nervous system or ophthalmologic sequelae. Methanol poisoning should be kept in mind in patients with diplopia and unexplained metabolic acidosis. Although most methanol intoxication cases occur after oral ingestion, it should be considered that methanol poisoning may occur transdermally.
Topics: Acidosis; Bandages; Bicarbonates; Ethanol; Female; Humans; Methanol; Middle Aged; Renal Dialysis; Skin Absorption
PubMed: 31823634
DOI: No ID Found -
British Journal of Anaesthesia Oct 2023Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic...
BACKGROUND
Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic diabetic ketoacidosis, particularly during times of physiologic stress, including fasting and surgery. Beyond case reports and series, a systematic description of perioperative metabolic effects of SGLT2 inhibitors is lacking.
METHODS
We examined the degree of anion gap acidosis, controlling for non-ketone anions, in patients undergoing surgery at Massachusetts General Hospital in 2016-22. We constructed a multivariable regression model incorporating known non-ketone contributors to the postoperative anion gap (albumin, lactate, estimated glomerular filtration rate, and preoperative anion gap), hold time, and interaction terms between hold time and three previously suggested risk factors for euglycaemic diabetic ketoacidosis: emergency surgery, cardiac surgery, and insulin use.
RESULTS
In 463 patients on SGLT2 inhibitors, we observed a strong association between decreased hold time and postoperative anion gap (P<0.001 in a univariable analysis; -0.43, 95% confidence interval [-0.76 to -0.11] change in anion gap per day held, P=0.01 in a multivariable analysis). A significant interaction between hold time and emergency surgery was observed, whereas there was no apparent interaction with insulin use or cardiac surgery.
CONCLUSIONS
These findings provide the first evidence that an anion gap acidosis, likely from ketoacids, develops in all patients who do not hold SGLT2 inhibitors before surgery rather than in an idiosyncratic few. If an SGLT2 inhibitor is unable to be stopped, postoperative monitoring of anion gap and serum ketones can help detect clinically significant euglycaemic diabetic ketoacidosis, particularly in those undergoing emergency surgery.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Acid-Base Equilibrium; Retrospective Studies; Acidosis; Insulins; Diabetes Mellitus, Type 2
PubMed: 37541949
DOI: 10.1016/j.bja.2023.06.063 -
Journal of the American Society of... May 2021Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH) in patients with... (Review)
Review
Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (, UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.
Topics: Acid-Base Equilibrium; Acidosis; Ammonia; Humans
PubMed: 33769949
DOI: 10.1681/ASN.2020101509 -
International Journal of Molecular... Feb 2024Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and... (Review)
Review
Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and plant-sourced food, particularly fruits and vegetables, generally yield bases when metabolized. Modern diets proportionately contain more animal-sourced than plant-sourced foods, are, thereby, generally net acid-producing, and so constitute an ongoing acid challenge. Acid accumulation severe enough to reduce serum bicarbonate concentration, i.e., manifesting as chronic metabolic acidosis, the most extreme end of the continuum of "acid stress", harms bones and muscles and appears to enhance the progression of chronic kidney disease (CKD). Progressive acid accumulation that does not achieve the threshold amount necessary to cause chronic metabolic acidosis also appears to have deleterious effects. Specifically, identifiable acid retention without reduced serum bicarbonate concentration, which, in this review, we will call "covert acidosis", appears to cause kidney injury and exacerbate CKD progression. Furthermore, the chronic engagement of mechanisms to mitigate the ongoing acid challenge of modern diets also appears to threaten health, including kidney health. This review describes the full continuum of "acid stress" to which modern diets contribute and the mechanisms by which acid stress challenges health. Ongoing research will develop clinically useful tools to identify stages of acid stress earlier than metabolic acidosis and determine if dietary acid reduction lowers or eliminates the threats to health that these diets appear to cause.
Topics: Animals; Bicarbonates; Acid-Base Equilibrium; Diet; Acidosis; Renal Insufficiency, Chronic
PubMed: 38397012
DOI: 10.3390/ijms25042336 -
Journal of Animal Science Aug 2020Acute and subacute ruminal acidosis (SARA) are common nutritional problems in both beef and dairy cattle. Therefore, the objective of this review is to describe how... (Review)
Review
Acute and subacute ruminal acidosis (SARA) are common nutritional problems in both beef and dairy cattle. Therefore, the objective of this review is to describe how ruminal Gram-negative bacteria could contribute to the pathogenesis of ruminal acidoses, by releasing lipopolysaccharides (LPS; a component of their cell wall) in the ruminal fluid. When cattle consume excessive amounts of highly fermentable carbohydrates without prior adaptation, normal fermentation become disrupted. The fermentation of these carbohydrates quickly decreases ruminal pH due to the accumulation of short-chain fatty acids and lactate in the rumen. As a consequence, ruminal epithelium may be damaged and tissue function could be impaired, leading to a possible translocation of pathogenic substances from the rumen into the bloodstream. Such changes in fermentation are followed by an increase in Gram-positive bacteria while Gram-negative bacteria decrease. The lyses of Gram-negative bacteria during ruminal acidosis increase LPS concentration in the ruminal fluid. Because LPS is a highly proinflammatory endotoxin in the circulatory system, past studies have raised concerns regarding ruminal LPS contribution to the pathogenesis of ruminal acidosis. Although animals that undergo these disorders do not always have an immune response, recent studies showed that different Gram-negative bacteria have different LPS composition and toxicity, which may explain the differences in immune response. Given the diversity of Gram-negative bacteria in the rumen, evaluating the changes in the bacterial community during ruminal acidosis could be used as a way to identify which Gram-negative bacteria are associated with LPS release in the rumen. By identifying and targeting ruminal bacteria with possible pathogenic LPS, nutritional strategies could be created to overcome, or at least minimize, ruminal acidosis.
Topics: Acidosis; Animals; Cattle; Cattle Diseases; Diet; Epithelium; Fatty Acids, Volatile; Fermentation; Gram-Negative Bacteria; Hydrogen-Ion Concentration; Lipopolysaccharides; Rumen
PubMed: 32761212
DOI: 10.1093/jas/skaa248 -
Seminars in Respiratory and Critical... Oct 2023Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer...
Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer system plays a pivotal role in maintaining acid-base homeostasis, and measurements of pH, PCO, and HCO are routinely used in the estimation of metabolic and respiratory disturbance severity. Hypoventilation and hyperventilation cause primary respiratory acidosis and primary respiratory alkalosis, respectively. Metabolic acidosis and metabolic alkalosis have numerous origins, that include alterations in acid or base intake, body fluid losses, abnormalities of intermediary metabolism, and renal, hepatic, and gastrointestinal dysfunction. The concept of the anion gap is used to categorize metabolic acidoses, and urine chloride excretion helps define metabolic alkaloses. Both the lungs and kidneys employ compensatory mechanisms to minimize changes in pH caused by various physiologic and disease disturbances. Treatment of acid-base disorders should focus primarily on correcting the underlying cause and the hemodynamic and electrolyte derangements that ensue. Specific therapies under certain conditions include renal replacement therapy, mechanical ventilation, respiratory stimulants or depressants, and inhibition of specific enzymes in intermediary metabolism disorders.
Topics: Humans; Acid-Base Imbalance; Hydrogen-Ion Concentration; Acid-Base Equilibrium; Acidosis; Alkalosis; Carbon Dioxide
PubMed: 37369215
DOI: 10.1055/s-0043-1770341 -
Scandinavian Journal of Clinical and... May 2023It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to...
It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to sulfate, and therefore the mEq sulfate excreted in the urine is counted as acid retained in the body. In this study we show that pH in fluids with constant [Na] and [HEPES] declines as sulfate ions are added, and we show that titratable acidity increases exactly with the equivalents of sulfate. Therefore, sulfate excretion in urine is also acid excretion . This is in accordance with the down-regulation of proximal sulfate reabsorption under acidosis and the observation that children with distal renal tubular acidosis may be sulfate depleted. These results are well explained using charge-balance modeling, which is based only on the three fundamental principles of electroneutrality, conservation of mass, and rules of dissociation as devised from physical chemistry. In contrast, the findings are in contrast to expectations from conventional narratives. These are unable to understand the decreasing pH as sulfate is added since no conventional acid is present. The results may undermine the traditional notion of endogenous acid production since in the case of sulfur balance, S oxidation and its excretion as sulfate exactly balance each other. Possible clinical correlates with these findings are discussed.
Topics: Child; Humans; Acid-Base Equilibrium; Sulfates; Acidosis; Sodium; Sulfur; Hydrogen-Ion Concentration
PubMed: 36988149
DOI: 10.1080/00365513.2023.2188607 -
QJM : Monthly Journal of the... Aug 2019
Topics: Acetaminophen; Acidosis; Aged; Analgesics, Non-Narcotic; Humans; Male; Pain Management; Pyrrolidonecarboxylic Acid
PubMed: 31086977
DOI: 10.1093/qjmed/hcz107