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Journal of Renal Nutrition : the... May 2023Studies have shown that low or high serum bicarbonate levels (reflecting metabolic acidosis or alkalosis) are associated with increased all-cause mortality rates in...
OBJECTIVE
Studies have shown that low or high serum bicarbonate levels (reflecting metabolic acidosis or alkalosis) are associated with increased all-cause mortality rates in moderate and advanced chronic kidney disease (CKD) cases. Correction of presumed acidosis using sodium bicarbonate, targeting serum levels around 22 mmol/L, has proven to be beneficial in delaying the progression of the disease and provided mortality benefit. A similar prognostic association may exist between uncorrected metabolic acidosis in chronic liver disease. Correcting it with sodium-containing salts may require more interventions due to increased sodium/fluid load. In patients with liver failure, a naturally alkalotic state, where sodium load is a concern, the impact of this intervention is unclear.
DESIGN
This study aims to generate proof of concept through a retrospective chart review in individuals with CKD-related metabolic acidosis and liver cirrhosis.
RESULT
Our analysis revealed a statistically significant association between the need for paracentesis and bicarbonate therapy. Our study has multiple drawbacks, including a retrospective chart review and limitation of data due to single-center patients.
CONCLUSION
We extrapolate that lowering bicarbonate targets in other clinical scenarios like liver failure, pregnancy, and cardiac failure may be prudent and will lead to a lower sodium load.
Topics: Humans; Bicarbonates; Retrospective Studies; Acidosis; Chronic Disease; Renal Insufficiency, Chronic; Sodium; Liver Diseases; Kidney; Liver Failure
PubMed: 36736470
DOI: 10.1053/j.jrn.2022.12.008 -
Iranian Journal of Kidney Diseases Jul 2018Chronic kidney disease is defined as a glomerular filtration rate lower than 60 mL/min/1.73 m2, which is regarded as a public health priority and part of the growing... (Review)
Review
Chronic kidney disease is defined as a glomerular filtration rate lower than 60 mL/min/1.73 m2, which is regarded as a public health priority and part of the growing burden of noncommunicable diseases. Reduced kidney function is concomitant with high levels of inflammatory factors, abnormal lipid profile, and anemia, as well as bone abnormalities, calcium deposition outside the bones, endothelial dysfunction, and cardiomyopathy. Furthermore, metabolic acidosis is a common complication in chronic kidney disease that is associated with secondary hyperparathyroidism and faster kidney disease progression. Effective preventive approaches may slow progression of chronic kidney disease and reduce the risk of subsequent morbidity and mortality. It seems that correction of metabolic acidosis slows down the decline in glomerular filtration rate and is one of the noble approaches. A diet rich in fruits and vegetables instead of bicarbonate therapy is feasible and economical and appears to have a positive effect on kidney hemodynamic function.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Diet, Healthy; Disease Progression; Fruit; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Kidney; Renal Insufficiency, Chronic; Treatment Outcome; Vegetables
PubMed: 30087214
DOI: No ID Found -
Nutrients Apr 2018Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic... (Review)
Review
Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8⁻1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.
Topics: Acid-Base Equilibrium; Acidosis; Diet, Protein-Restricted; Dietary Supplements; Fruit; Glomerular Filtration Rate; Humans; Kidney; Nutritive Value; Recommended Dietary Allowances; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Vegetables
PubMed: 29677110
DOI: 10.3390/nu10040512 -
Clinical Nutrition (Edinburgh, Scotland) Nov 2023This review summarises some of my work on fluid and electrolyte balance over the past 25 years and shows how the studies have influenced clinical practice. Missing... (Review)
Review
This review summarises some of my work on fluid and electrolyte balance over the past 25 years and shows how the studies have influenced clinical practice. Missing pieces in the jigsaw are filled in by summarising the work of others. The main theme is the biochemical, physiological and clinical problems caused by inappropriate use of saline solutions including the hyperchloraemic acidosis caused by 0.9% saline. The importance of accurate and near-zero fluid balance in clinical practice is also emphasised. Perioperative fluid and electrolyte therapy has important effects on clinical outcome in a U-shaped dose response fashion, in which excess or deficit progressively increases complications and worsens outcome. Salt and water overload, with weight gain in excess of 2.5 kg worsens surgical outcome, impairs gastrointestinal function and increases the risk of anastomotic dehiscence. Hyperchloraemic acidosis caused by overenthusiastic infusion of 0.9% saline leads to adverse outcomes and dysfunction of many organ systems, especially the kidney. Salt and water deficit causes similar adverse effects as fluid overload at the cellular level and also leads to worse outcomes. Serum albumin is shown to be affected mainly by dilution and inflammation and is not a good nutritional marker. These findings have been incorporated in the British consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients (GIFTASUP) and National Institute for Health and Care Excellence (NICE) guidelines on intravenous fluid therapy in adults in hospital and are helping change clinical practice and improve outcomes.
Topics: Adult; Humans; Saline Solution; Fluid Therapy; Water-Electrolyte Balance; Sodium Chloride; Acidosis; Water
PubMed: 37820519
DOI: 10.1016/j.clnu.2023.09.029 -
Journal of Biomedical Science Jan 2024During sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in...
BACKGROUND
During sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In addition, septic patients have an altered cell metabolism that leads to lactic acidosis. Septic patients suffering from lactic acidosis have a high risk of mortality. In addition, septic survivors are at risk of secondary vascular disease. The underlying mechanisms of whether and how lactic acidosis leads to the changes in VSMCs is not well understood. The aim of this study was to comprehensively investigate the effect of lactic acidosis on VSMCs and additionally compare the effects with those induced by pure acidosis and sodium lactate.
METHODS
Primary human aortic smooth muscle cells (HAoSMCs) were treated for 48 h with lactic acidosis (LA_pH 6.8), hydrochloric acid (HCl_pH 6.8), sodium lactate (Na-lactate_pH 7.4) and the respective controls (ctrl._pH 7.4; hyperosmolarity control: mannitol_pH 7.4) and comparatively analyzed for changes in (i) transcriptome, (ii) energy metabolism, and (iii) phenotype.
RESULTS
Both types of acidosis led to comparable and sustained intracellular acidification without affecting cell viability. RNA sequencing and detailed transcriptome analysis revealed more significant changes for lactic acidosis than for hydrochloric acidosis, with lactate being almost ineffective, suggesting qualitative and quantitative synergism of acidosis and lactate. Bioinformatic predictions in energy metabolism and phenotype were confirmed experimentally. Lactic acidosis resulted in strong inhibition of glycolysis, glutaminolysis, and altered mitochondrial respiration which reduced cellular ATP content, likely due to increased TXNIP expression and altered NAD/NADH ratio. Hydrochloric acidosis induced significantly smaller effects without changing the NAD/NADH ratio, with the ATP content remaining constant. These metabolic changes led to osteo-/chondrogenic/senescent transdifferentiation of VSMCs, with the effect being more pronounced in lactic acidosis than in pure acidosis.
CONCLUSIONS
Overall, lactic acidosis exerted a much stronger effect on energy metabolism than pure acidosis, whereas lactate had almost no effect, reflecting the qualitative and quantitative synergism of acidosis and lactate. As a consequence, lactic acidosis may lead to acute functional impairments of VSMC, sustained perturbations of the transcriptome and cellular dedifferentiation. Moreover, these effects may contribute to the acute and prolonged vascular pathomechanisms in septic patients.
Topics: Humans; Acidosis, Lactic; Muscle, Smooth, Vascular; NAD; Sodium Lactate; Acidosis; Lactic Acid; Sepsis; Adenosine Triphosphate
PubMed: 38195466
DOI: 10.1186/s12929-023-00992-6 -
Current Eye Research Jul 2018Changes in retinal pH may contribute to a variety of eye diseases. To study the effect of acidosis alone, we induced systemic metabolic acidosis and hypothesized that...
PURPOSE
Changes in retinal pH may contribute to a variety of eye diseases. To study the effect of acidosis alone, we induced systemic metabolic acidosis and hypothesized that the retina would respond with altered expression of genes involved in acid/base regulation.
METHODS
Systemic metabolic acidosis was induced in Long-Evans rats for up to 2 weeks by adding NHCl to the drinking water. After 2 weeks, venous pH was 7.25 ± 0.08 (SD) and [HCO] was 21.4 ± 4.6 mM in acidotic animals; pH was 7.41 ± 0.03 and [HCO] was 30.5 ± 1.0 mM in controls. Retinal mRNAs were quantified by quantitative reverse transcription polymerase chain reaction. Protein was quantified with Western blots and localized by confocal microscopy. Retinal [H] was measured in vivo with pH microelectrodes in animals subjected to metabolic acidosis and in controls.
RESULTS
NHCl in drinking water or given intravenous was effective in acidifying the retina. Cariporide, a blocker of Na/H exchange, further acidified the retina. Metabolic acidosis for 2 weeks led to increases of 40-100% in mRNA for carbonic anhydrase isoforms II (CA-II) and XIV (CA-XIV) and acid-sensing ion channels 1 and 4 (ASIC1 and ASIC4) (all p < 0.005). Expression of anion exchange protein 3 (AEP-3) and Na/H exchanger (NHE)-1 also increased by ≥50% (both p < 0.0001). Changes were similar after 1 week of acidosis. Protein for AEP-3 doubled. NHE-1 co-localized with vascular markers, particularly in the outer plexiform layer. CA-II was located in the neural parenchyma of the ganglion cell layer and diffusely in the rest of the inner retina.
CONCLUSIONS
The retina responds to systemic acidosis with increased expression of proton and bicarbonate exchangers, carbonic anhydrase, and ASICs. While responses to acidosis are usually associated with renal regulation, these studies suggest that the retina responds to changes in local pH presumably to control its acid/base environment in response to systemic acidosis.
Topics: Acidosis; Animals; Blotting, Western; Disease Models, Animal; Electroretinography; Eye Proteins; Gene Expression Regulation; Hydrogen-Ion Concentration; Immunohistochemistry; Male; RNA; Rats; Rats, Long-Evans; Retina; Reverse Transcriptase Polymerase Chain Reaction; Sodium-Hydrogen Exchangers
PubMed: 29641914
DOI: 10.1080/02713683.2018.1458882 -
Clinical Journal of the American... Jan 2018
Topics: Acidosis; Bicarbonates; Humans; Renal Insufficiency, Chronic; Uremia
PubMed: 29102960
DOI: 10.2215/CJN.11771017 -
Cancer Metastasis Reviews Jun 2019Cancer development is a complex process that follows an intricate scenario with a dynamic interplay of selective and adaptive steps and an extensive cast of molecules... (Review)
Review
Cancer development is a complex process that follows an intricate scenario with a dynamic interplay of selective and adaptive steps and an extensive cast of molecules and signaling pathways. Solid tumor initially grows as an avascular bulk of cells carrying oncogenic mutations until diffusion distances from the nearest functional blood vessels limit delivery of nutrients and oxygen on the one hand and removal of metabolic waste on the other one. These restrictions result in regional hypoxia and acidosis that select for adaptable tumor cells able to promote aberrant angiogenesis, remodel metabolism, acquire invasiveness and metastatic propensity, and gain therapeutic resistance. Tumor cells are thereby endowed with capability to survive and proliferate in hostile microenvironment, communicate with stroma, enter circulation, colonize secondary sites, and generate metastases. While the role of oncogenic mutations initializing and driving these processes is well established, a key contribution of non-genomic, landscaping molecular players is still less appreciated despite they can equally serve as viable targets of anticancer therapies. Carbonic anhydrase IX (CA IX) is one of these players: it is induced by hypoxia, functionally linked to acidosis, implicated in invasiveness, and correlated with therapeutic resistance. Here, we summarize the available experimental evidence supported by accumulating preclinical and clinical data that CA IX can contribute virtually to each step of cancer progression path via its enzyme activity and/or non-catalytic mechanisms. We also propose that targeting tumor cells that express CA IX may provide therapeutic benefits in various settings and combinations with both conventional and newly developed treatments.
Topics: Acidosis; Animals; Carbonic Anhydrase IX; Cell Hypoxia; Humans; Neoplasms
PubMed: 31076951
DOI: 10.1007/s10555-019-09799-0 -
Kidney International May 2016Metabolic acidosis is a common complication of chronic kidney disease; it is typically caused by the accumulation of sulfate, phosphorus, and organic anions. Metabolic... (Review)
Review
Metabolic acidosis is a common complication of chronic kidney disease; it is typically caused by the accumulation of sulfate, phosphorus, and organic anions. Metabolic acidosis is correlated with several adverse outcomes, such as morbidity, hospitalization, and mortality. Thus, correction of metabolic acidosis is fundamental for the adequate management of many systemic complications of chronic kidney disease. In patients undergoing hemodialysis, acid-base homeostasis depends on many factors including the following: net acid production, amount of alkali given by the dialysate bath, duration of the interdialytic period, and residual diuresis, if any. Recent literature data suggest that the development of metabolic alkalosis after dialysis may contribute to adverse clinical outcomes. Our review is focused on the potential effects of different dialysate bicarbonate concentrations on hard outcomes such as mortality. Unfortunately, no randomized studies exist about this issue. Acid-base equilibrium is a complex and vital system whose regulation is impaired in chronic kidney disease. We await further studies to assess the extent to which acid-base status is a major determinant of overall survival in patients undergoing hemodialysis. For the present, the clinician should understand that target values for predialysis serum bicarbonate concentration have been established primarily based on observational studies and expert opinion. Based on this, we should keep the predialysis serum bicarbonate level at least at 22 mmol/l. Furthermore, a specific focus should be addressed by the attending nephrologist to the clinical and nutritional status of the major outliers on both the acid and alkaline sides of the curve.
Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Hemodialysis Solutions; Humans; Hydrogen-Ion Concentration; Male; Models, Biological; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 26924048
DOI: 10.1016/j.kint.2016.01.010 -
Animal : An International Journal of... Mar 2020Rumen sensors provide specific information to help understand rumen functioning in relation to health disorders and to assist in decision-making for farm management.... (Review)
Review
Rumen sensors provide specific information to help understand rumen functioning in relation to health disorders and to assist in decision-making for farm management. This review focuses on the use of rumen sensors to measure ruminal pH and discusses variation in pH in both time and location, pH-associated disorders and data analysis methods to summarize and interpret rumen pH data. Discussion on the use of rumen sensors to measure redox potential as an indication of the fermentation processes is also included. Acids may accumulate and reduce ruminal pH if acid removal from the rumen and rumen buffering cannot keep pace with their production. The complexity of the factors involved, combined with the interactions between the rumen and the host that ultimately determine ruminal pH, results in large variation among animals in their pH response to dietary or other changes. Although ruminal pH and pH dynamics only partially explain the typical symptoms of acidosis, it remains a main indicator and may assist to optimize rumen function. Rumen pH sensors allow continuous monitoring of pH and of diurnal variation in pH in individual animals. Substantial drift of non-retrievable rumen pH sensors, and the difficulty to calibrate these sensors, limits their application. Significant within-day variation in ruminal pH is frequently observed, and large distinct differences in pH between locations in the rumen occur. The magnitude of pH differences between locations appears to be diet dependent. Universal application of fixed conversion factors to correct for absolute pH differences between locations should be avoided. Rumen sensors provide high-resolution kinetics of pH and a vast amount of data. Commonly reported pH characteristics include mean and minimum pH, but these do not properly reflect severity of pH depression. The area under the pH × time curve integrates both duration and extent of pH depression. The use of this characteristic, as well as summarizing parameters obtained from fitting equations to cumulative pH data, is recommended to identify pH variation in relation to acidosis. Some rumen sensors can also measure the redox potential. This measurement helps to understand rumen functioning, as the redox potential of rumen fluid directly reflects the microbial intracellular redox balance status and impacts fermentative activity of rumen microorganisms. Taken together, proper assessment and interpretation of data generated by rumen sensors requires consideration of their limitations under various conditions.
Topics: Acidosis; Animals; Cattle; Cattle Diseases; Diet; Female; Fermentation; Hydrogen-Ion Concentration; Oxidation-Reduction; Rumen
PubMed: 32024561
DOI: 10.1017/S1751731119003112