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Kidney International Jun 2022The homeostatic regulation of a stable systemic pH is of critical importance for mammalian survival. During metabolic acidosis (a reduction in systemic pH caused by a... (Review)
Review
The homeostatic regulation of a stable systemic pH is of critical importance for mammalian survival. During metabolic acidosis (a reduction in systemic pH caused by a primary decrease in serum bicarbonate concentration), as seen in clinical disorders such as the later stages of chronic kidney disease, renal tubular acidosis, or chronic diarrhea, bone buffers the accumulated acid; however, this homeostatic function of the skeleton occurs at the expense of the bone mineral content and leads to decreased bone quality. During short-term studies to model acute metabolic acidosis, there is initial physiochemical bone mineral dissolution, releasing carbonate and phosphate proton buffers into the extracellular fluid. In addition, there is net proton influx into the mineral with release of bone sodium and potassium. During long-term studies to model chronic metabolic acidosis, there is also inhibition of osteoblast activity, resulting in reduced bone formation, and an increase in osteoclast activity, resulting in increased bone resorption and release of calcium and anionic proton buffers. These physicochemical and cell-mediated bone responses to metabolic acidosis, in addition to an acidosis-induced increased urine calcium excretion, without a corresponding increase in intestinal calcium absorption, induce a net loss of body calcium that is almost certainly derived from the mineral stores of bone.
Topics: Acidosis; Animals; Bone and Bones; Calcium; Hydrogen-Ion Concentration; Mammals; Phosphates; Protons
PubMed: 35351460
DOI: 10.1016/j.kint.2022.02.032 -
Advances in Chronic Kidney Disease Jul 2022Metabolic acidosis is common in people with chronic kidney disease and can contribute to functional decline, morbidity, and mortality. One avenue through which metabolic... (Review)
Review
Metabolic acidosis is common in people with chronic kidney disease and can contribute to functional decline, morbidity, and mortality. One avenue through which metabolic acidosis can result in these adverse clinical outcomes is by negatively impacting skeletal muscle; this can occur through several pathways. First, metabolic acidosis promotes protein degradation and impairs protein synthesis, which lead to muscle breakdown. Second, metabolic acidosis hinders mitochondrial function, which decreases oxidative phosphorylation and reduces energy production. Third, metabolic acidosis directly limits muscle contraction. The purpose of this review is to examine the specific mechanisms of each pathway through which metabolic acidosis affects muscle, the impact of metabolic acidosis on physical function, and the effect of treating metabolic acidosis on functional outcomes.
Topics: Acidosis; Humans; Muscles; Renal Insufficiency, Chronic
PubMed: 36175077
DOI: 10.1053/j.ackd.2022.04.010 -
Biomedicine & Pharmacotherapy =... Feb 2023Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and... (Review)
Review
Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.
Topics: Humans; Hyperkalemia; Bicarbonates; Acidosis; Potassium; Renal Insufficiency, Chronic
PubMed: 36916426
DOI: 10.1016/j.biopha.2022.114197 -
Heart & Lung : the Journal of Critical... 2022Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited.
OBJECTIVES
To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS.
METHODS
The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model.
RESULTS
The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78-0.74; p = 0.12) with heterogeneity of 85%.
CONCLUSION
Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS.
Topics: Acidosis; Adult; Diabetes Mellitus; Diabetic Ketoacidosis; Electrolytes; Fluid Therapy; Humans; Resuscitation
PubMed: 35358905
DOI: 10.1016/j.hrtlng.2022.03.014 -
Advances in Chronic Kidney Disease Jul 2022The various mechanisms responsible for the development of metabolic acidosis are briefly reviewed, and the metabolic acidoses are categorized both by mechanism and by... (Review)
Review
The various mechanisms responsible for the development of metabolic acidosis are briefly reviewed, and the metabolic acidoses are categorized both by mechanism and by the presence or absence of an increased anion gap. When a diagnosis of metabolic acidosis is established, it becomes imperative to identify the primary causative etiology as quickly as possible. This is often readily apparent from the history and physical exam (ie, diabetic ketoacidosis when the glucose is very high in a patient with diabetes mellitus; lactic acidosis in a patient with sepsis and hypotension, etc.). However, when the etiology is not obvious, it is very helpful to determine if the metabolic acidosis is of the hyperchloremic or high-anion-gap type (or a combination of both). Once this categorization has been established, a stepwise consideration of each of the potential causative etiologies will usually direct the clinician to order the appropriate diagnostic studies.
Topics: Acid-Base Imbalance; Acidosis; Anions; Glucose; Humans; Physical Examination
PubMed: 36175073
DOI: 10.1053/j.ackd.2022.07.004 -
Clinical Journal of the American... Feb 2021
Topics: Acidosis; Ammonium Compounds; Animals; Bicarbonates; Citric Acid; Disease Progression; Humans; Hydrogen-Ion Concentration; Renal Insufficiency, Chronic
PubMed: 32769096
DOI: 10.2215/CJN.07990520 -
International Journal of Molecular... May 2024Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor... (Review)
Review
Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.
Topics: Humans; Acidosis; Renal Insufficiency, Chronic; Sodium Bicarbonate; Animals; Treatment Outcome
PubMed: 38791238
DOI: 10.3390/ijms25105187 -
Annals of Hepatology 2022In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the... (Review)
Review
In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.
Topics: Acidosis; Alkalosis; Humans; Liver Cirrhosis; Liver Diseases; Urea
PubMed: 35074477
DOI: 10.1016/j.aohep.2022.100675 -
BMJ Case Reports Feb 2024Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged...
Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged administration of linezolid, lactic acidosis is a rare adverse drug reaction. We present the case of a patient on linezolid for disseminated multidrug-resistant tuberculosis who presented with vomiting, dyspnoea, hypotension and high anion gap metabolic acidosis. The initial presentation mimicked sepsis syndrome. Ketoacidosis and renal dysfunction were ruled out. There was no history of ingestion of toxins/toxic alcohols. Sepsis was unlikely because extensive radiological and microbiological testing could not identify an infection. Given the possibility of linezolid-induced lactic acidosis (LILA), linezolid was discontinued on admission. The patient's lactic acidosis resolved, and his overall condition improved. A retrospective diagnosis of LILA was thus established. LILA should be considered when patients on linezolid present with lactic acidosis and other causes for the lactic acidosis have been ruled out.
Topics: Humans; Linezolid; Acidosis, Lactic; Retrospective Studies; Anti-Bacterial Agents; Acidosis
PubMed: 38331448
DOI: 10.1136/bcr-2023-259335 -
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