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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 -
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 -
Ugeskrift For Laeger Aug 2021It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and... (Review)
Review
It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and functions to dampen reductions in intracellular pH through lactate-H+ cotransport to the extracellular space. Though this may give rise to elevated blood lactate, increased lactate production is not the cause of metabolic acidosis in such instances. "Lactic acidosis" is thus an inappropriate term as it indicates causality and in this review, we suggest that in the future, the term "hyperlactataemia-associated metabolic acidosis" should be used instead.
Topics: Acidosis; Acidosis, Lactic; Humans; Lactic Acid
PubMed: 34477100
DOI: No ID Found -
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 -
The Veterinary Clinics of North... Jul 2023Beef cattle are less prone to metabolic diseases as compared with dairy cattle; however, there are disease entities of concern in feedlot and cow-calf beef cattle... (Review)
Review
Beef cattle are less prone to metabolic diseases as compared with dairy cattle; however, there are disease entities of concern in feedlot and cow-calf beef cattle operations. In one study, a prevalence of 2% was found for ruminant acidosis in a feedlot; however, there is little prevalence information published with regard to metabolic diseases in beef cattle.1 Metabolic diseases covered in this article are hypomagnesemia, ruminal acidosis, and all of the common sequelae, polioencephalomalacia, manganese deficiency, and protein-energy malnutrition (PEM).
Topics: Female; Cattle; Animals; Cattle Diseases; Metabolic Diseases; Acidosis
PubMed: 37032297
DOI: 10.1016/j.cvfa.2023.02.011 -
Journal of the American Society of... Mar 2024Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing... (Randomized Controlled Trial)
Randomized Controlled Trial
SIGNIFICANCE STATEMENT
Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated.
BACKGROUND
Metabolic acidosis is common in 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 (eGFR of 20-40 ml/min per 1.73 m 2 ) 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 end point of CKD progression, defined as the development of ESKD (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 per 1.73 m 2 , 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. After 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 approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 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.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
VALOR-CKD, NCT03710291 .
Topics: Humans; Bicarbonates; Hydrochloric Acid; Acidosis; Renal Insufficiency, Chronic; Polymers
PubMed: 38261535
DOI: 10.1681/ASN.0000000000000292 -
Deutsche Medizinische Wochenschrift... Nov 2020Acid-base disorders due to different etiologies are frequently encountered in daily clinical practice and may result in life-threatening situations. Basic knowledge of...
Acid-base disorders due to different etiologies are frequently encountered in daily clinical practice and may result in life-threatening situations. Basic knowledge of the diagnostic and therapeutic approach of acid-base disorders is therefore essential for every clinician. Acid-base disorders should be treated according to their underlying etiology. Therefore, diagnosis of the underlying etiology is the critical step in the process of care for patients with acid-base disorders. Undirected buffering with HCO should be avoided, since the application of HCO might lead to severe side effects. A strict diagnostic pathway for the diagnosis of acid-base disorders is required, which should be vigorously applied:- analysis of the pH to classify acidemia or alkalemia- analysis of pCO and HCO to classify the primary acid base disorder- analysis of the adequate regulation in order to detect additional acid-base disorders- analysis of the anion gap and the relationship of the anion gap vs. the change in HCO to detect further metabolic disordersMetabolic acidosis can be divided into two main etiologies:- acidosis with addition of acid with increased anion gap,- acidosis with loss of HCO with normal anion gap.
Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Humans
PubMed: 33142331
DOI: 10.1055/a-0670-6038 -
Clinical Journal of the American... Aug 2021Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury.... (Review)
Review
Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.
Topics: Acid-Base Equilibrium; Acidosis; Acids; Bicarbonates; Chronic Disease; Diet; Glomerular Filtration Rate; Humans; Kidney Diseases; Stress, Physiological
PubMed: 33741720
DOI: 10.2215/CJN.17541120 -
Cells May 2021Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the... (Review)
Review
Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities.
Topics: Acidosis; Animals; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Ductal, Breast; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Lysosomes; Molecular Targeted Therapy; Tumor Microenvironment; Warburg Effect, Oncologic
PubMed: 34067971
DOI: 10.3390/cells10051188 -
Emergency Medicine Clinics of North... Nov 2023Metabolic acid-base disturbances are frequently encountered in the emergency department, and many of these patients are critically ill. In the evaluation of patients... (Review)
Review
Metabolic acid-base disturbances are frequently encountered in the emergency department, and many of these patients are critically ill. In the evaluation of patients with these maladies, it is important for the emergency clinician to determine the cause, which can usually be elicited from a thorough history and physical examination. There are several mnemonics that can be used to form an appropriate list of potential causes. Most of the time, the management of these patients requires no specific treatment of the acid-base status but, rather, requires treatment of the underlying disorder that is causing the acid-base disturbance.
Topics: Humans; Acid-Base Imbalance; Acidosis; Alkalosis
PubMed: 37758428
DOI: 10.1016/j.emc.2023.06.008