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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 -
PLoS Pathogens Jan 2021Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can... (Review)
Review
Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.
Topics: Acidosis, Lactic; Humans; Malaria; Plasmodium
PubMed: 33411818
DOI: 10.1371/journal.ppat.1009122 -
Journal of the American Society of... Jun 2017
Topics: Acidosis; Allografts; Humans; Kidney; Kidney Transplantation; Transplantation, Homologous
PubMed: 28348064
DOI: 10.1681/ASN.2017020133 -
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 -
Journal of the American Society of... Feb 2018Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical... (Review)
Review
Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.
Topics: Acidosis; Acids; Alkalies; Asymptomatic Diseases; Bone Demineralization, Pathologic; Carbon Dioxide; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Risk Factors; Sodium Bicarbonate
PubMed: 29030467
DOI: 10.1681/ASN.2017040422 -
Clinical Journal of the American... Oct 2018
Topics: Acidosis; Cardiovascular Diseases; Cross-Over Studies; Humans; Pilot Projects; Renal Insufficiency, Chronic
PubMed: 30237218
DOI: 10.2215/CJN.10120818 -
Seminars in Nephrology Mar 2023Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be... (Review)
Review
Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be excreted fully by the kidney. A reduction in urine net acid excretion coupled with a high nonvolatile acid load may play a role in its pathogenesis. Diet is important in generation of the nonvolatile acid load. Acids are produced from metabolism of dietary protein and from the endogenous production of organic anions from neutral precursors. Acids can be balanced by alkali precursors ingested in the diet in the form of combustible organic anions. These typically are reflected indirectly by the excess of mineral cations to mineral anions in a food or diet. These principles underscore widely used methods to estimate the nonvolatile acid load from dietary intake using formulas such as the net endogenous acid production equation and the potential renal acid load equation. Empiric data largely validate these paradigms with high net endogenous acid production and potential renal acid load contributed by foods such as protein, grains, and dairy, and low net endogenous acid production and potential renal acid load contributed by fruits and vegetables along with corresponding dietary patterns. Although further studies are needed to understand the health benefits of altering nonvolatile acid load via diet, this review provides a detailed assessment on our current understanding of the role of diet in chronic kidney disease-related acidosis, providing an updated resource for researchers and clinicians.
Topics: Humans; Diet; Renal Insufficiency, Chronic; Acidosis; Acid-Base Equilibrium; Anions; Minerals
PubMed: 37898028
DOI: 10.1016/j.semnephrol.2023.151425 -
Cellular and Molecular Life Sciences :... Mar 2020Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with... (Review)
Review
Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with enzyme activity. ζ-crystallin is a moonlighting protein endowed with two main different functions: (1) mRNA binding with stabilizing activity; (2) NADPH:quinone oxidoreductase. ζ-crystallin has been clearly demonstrated to stabilize mRNAs encoding proteins involved in renal glutamine catabolism during metabolic acidosis resulting in ammoniagenesis and bicarbonate ion production that concur to compensate such condition. ζ-crystallin binds also mRNAs encoding for antiapoptotic proteins, such as Bcl-2 in leukemia cells. On the other hand, the physiological role of its enzymatic activity is still elusive. Gathering research evidences and data mined from public databases, we provide a framework where all the known ζ-crystallin properties are called into question, making it a hypothetical pivotal player in cancer, allowing cells to hijack or subjugate the acidity response mechanism to increase their ability to resist oxidative stress and apoptosis, while fueling their glutamine addicted metabolism.
Topics: Acidosis; Ammonia; Animals; Apoptosis; Glutamine; Humans; Neoplasms; Oxidative Stress; Protein Binding; RNA, Messenger; zeta-Crystallins
PubMed: 31563996
DOI: 10.1007/s00018-019-03301-3 -
European Journal of Medical Research May 2024The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several... (Review)
Review
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
Topics: Humans; Acidosis; Acid-Base Imbalance; Acid-Base Equilibrium; Alkalosis
PubMed: 38735983
DOI: 10.1186/s40001-024-01796-6 -
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