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Journal of Cachexia, Sarcopenia and... Dec 2023Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass... (Meta-Analysis)
Meta-Analysis Review
Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m , and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P < 0.001) and functionality assessed with the sit-to-stand test (SMD -0.31 [95% CI -0.52 to 0.11], P = 0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.
Topics: Humans; Male; Middle Aged; Aged; Female; Dietary Proteins; Hand Strength; Renal Insufficiency, Chronic; Acidosis; Muscles
PubMed: 37728018
DOI: 10.1002/jcsm.13330 -
American Journal of Physiology. Renal... Oct 2021Chronic metabolic acidosis stimulates cell-mediated net Ca efflux from bone mediated by increased osteoblastic cyclooxygenase 2, leading to prostaglandin E-induced...
Chronic metabolic acidosis stimulates cell-mediated net Ca efflux from bone mediated by increased osteoblastic cyclooxygenase 2, leading to prostaglandin E-induced stimulation of receptor activator of NF-κB ligand-induced osteoclastic bone resorption. Ovarian cancer G protein-coupled receptor-1 (OGR1), an osteoblastic H-sensing G protein-coupled receptor, is activated by acidosis and leads to increased bone resorption. As regulator of G protein signaling (RGS) proteins limit GPCR signaling, we tested whether RGS proteins themselves are regulated by metabolic acidosis. Primary osteoblasts were isolated from neonatal mouse calvariae and incubated in physiological neutral or acidic (MET) medium. Cells were collected, and RNA was extracted for real-time PCR analysis with mRNA levels normalized to ribosomal protein L13a. , , , , , , and mRNA did not differ between MET and neutral medium; however, by 30 min, MET decreased , which persisted for 60 min and 3 h. Incubation of osteoblasts with the OGR1 inhibitor CuCl inhibited the MET-induced increase in mRNA. Gallein, a specific inhibitor of Gβγ signaling, was used to determine if downstream signaling by the βγ-subunit was critical for the response to acidosis. Gallein decreased net Ca efflux from calvariae and cyclooxygenase 2 and receptor activator of NF-κB ligand gene expression from isolated osteoblasts. These results indicate that regulation of RGS16 plays an important role in modulating the response of the osteoblastic GPCR OGR1 to metabolic acidosis and subsequent stimulation of osteoclastic bone resorption. The results presented in this study indicate that regulation of regulator of G protein signaling 16 and G protein signaling in the osteoblast plays an important role in modulating the response of osteoblastic ovarian cancer G protein-coupled receptor 1 (OGR1) to metabolic acidosis and the subsequent stimulation of osteoclastic bone resorption. Further characterization of the regulation of OGR1 in metabolic acidosis-induced bone resorption will help in understanding bone loss in acidotic patients with chronic kidney disease.
Topics: Acidosis; Animals; Bicarbonates; Carbon Dioxide; Cells, Cultured; GTP-Binding Proteins; Gene Expression Regulation; Hydrogen-Ion Concentration; Mice; Osteoblasts; RGS Proteins; RNA; Xanthenes
PubMed: 34396788
DOI: 10.1152/ajprenal.00166.2021 -
Nephron 2018The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance.... (Review)
Review
The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease.
Topics: Acid-Base Imbalance; Acidosis; Ammonium Compounds; Disease Progression; Humans; Renal Insufficiency, Chronic
PubMed: 29050011
DOI: 10.1159/000481892 -
Cancer Metastasis Reviews Jun 2019While cancer is commonly described as "a disease of the genes," it is also associated with massive metabolic reprogramming that is now accepted as a disease "Hallmark."... (Review)
Review
While cancer is commonly described as "a disease of the genes," it is also associated with massive metabolic reprogramming that is now accepted as a disease "Hallmark." This programming is complex and often involves metabolic cooperativity between cancer cells and their surrounding stroma. Indeed, there is emerging clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. The most commonly observed and well-studied metabolic adaptation in cancers is the fermentation of glucose to lactic acid, even in the presence of oxygen, also known as "aerobic glycolysis" or the "Warburg Effect." Much has been written about the mechanisms of the Warburg effect, and this remains a topic of great debate. However, herein, we will focus on an important sequela of this metabolic program: the acidification of the tumor microenvironment. Rather than being an epiphenomenon, it is now appreciated that this acidosis is a key player in cancer somatic evolution and progression to malignancy. Adaptation to acidosis induces and selects for malignant behaviors, such as increased invasion and metastasis, chemoresistance, and inhibition of immune surveillance. However, the metabolic reprogramming that occurs during adaptation to acidosis also introduces therapeutic vulnerabilities. Thus, tumor acidosis is a relevant therapeutic target, and we describe herein four approaches to accomplish this: (1) neutralizing acid directly with buffers, (2) targeting metabolic vulnerabilities revealed by acidosis, (3) developing acid-activatable drugs and nanomedicines, and (4) inhibiting metabolic processes responsible for generating acids in the first place.
Topics: Acidosis; Animals; Buffers; Humans; Hydrogen-Ion Concentration; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms
PubMed: 30911978
DOI: 10.1007/s10555-019-09792-7 -
Advances in Chronic Kidney Disease Jul 2022Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more... (Review)
Review
Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more advanced stages of CKD, these homeostatic processes are no longer adequate, resulting in metabolic acidosis. Potential deleterious effects of chronic metabolic acidosis in CKD, including muscle wasting, bone demineralization, hyperkalemia, and more rapid progression of CKD, have been well cataloged. Based primarily upon concerns related to nutrition and bone disease, early Kidney Disease Outcomes Quality Initiative guidelines recommended treating metabolic acidosis with alkali therapy targeting a serum bicarbonate ≥22 mEq/L. More recent guidelines have suggested similar targets based upon potential slowing of CKD progression. However, appropriately powered, long-term, randomized controlled trials to study efficacy and safety of alkali therapy for these outcomes are largely lacking. As a result, practice among physicians varies, underscoring the complexity of treatment of chronic metabolic acidosis in real-world CKD practice. Novel treatment approaches and rigorous phase 3 trials may resolve some of this controversy in the coming years. Metabolic acidosis is an important complication of CKD, and where it "falls" in the priority schema of CKD care will depend upon the generation of strong clinical evidence.
Topics: Acidosis; Alkalies; Bicarbonates; Humans; Kidney; Renal Insufficiency, Chronic
PubMed: 36175070
DOI: 10.1053/j.ackd.2022.05.002 -
Journal of Zhejiang University.... Mar 2016The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of... (Review)
Review
The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Chlorides; Hemodynamics; Humans; Kidney; Sodium Chloride
PubMed: 26984838
DOI: 10.1631/jzus.B1500201 -
Journal of Nutritional Science 2022Contemporary diets in Western countries are largely acid-inducing and deficient in potassium alkali salts, resulting in low-grade metabolic acidosis. The chronic... (Review)
Review
Contemporary diets in Western countries are largely acid-inducing and deficient in potassium alkali salts, resulting in low-grade metabolic acidosis. The chronic consumption of acidogenic diets abundant in animal-based foods (meats, dairy, cheese and eggs) poses a substantial challenge to the human body's buffering capacities and chronic retention of acid wherein the progressive loss of bicarbonate stores can cause cellular and tissue damage. An elevated dietary acid load (DAL) has been associated with systemic inflammation and other adverse metabolic conditions. In this narrative review, we examine DAL quantification methods and index observational and clinical evidence on the role of plant-based diets, chiefly vegetarian and vegan, in reducing DAL. Quantitation of protein and amino acid composition and of intake of alkalising organic potassium salts and magnesium show that plant-based diets are most effective at reducing DAL. Results from clinical studies and recommendations in the form of expert committee opinions suggest that for a number of common illnesses, wherein metabolic acidosis is a contributing factor, the regular inclusion of plant-based foods offers measurable benefits for disease prevention and management. Based on available evidence, dietary shifts toward plant-based nutrition effectively reduces dietary-induced, low-grade metabolic acidosis.
Topics: Humans; Diet, Vegetarian; Salts; Diet; Acidosis; Potassium
PubMed: 36405093
DOI: 10.1017/jns.2022.93 -
Archivos Espanoles de Urologia Jan 2021Renal tubular acidosis (RTA) is a set of raredis orders in which the renal tubule is unable to excreteacid normally and there by maintain normal acid-basebalance,...
Renal tubular acidosis (RTA) is a set of raredis orders in which the renal tubule is unable to excreteacid normally and there by maintain normal acid-basebalance, resulting in a complete or incomplete metabolicacidosis. In distal RTA (dRTA, also known as classicalor type 1 RTA), there is a defect in excreting H+ ionsalong the distal nephron (distal tubule and collectingduct), leading to an alkaline urinary pH with calcium phosphate precipitation and stones. Causes of dRTAinclude genetic mutations, autoimmune disease, and some drugs.Clinical manifestations of the genetic forms of dRTA typically occur during childhood and may vary from mildclinical symptoms, such as a mild metabolic acidosis, hypokalaemia,and incidental detection of kidney stones, to more serious manifestations such as failure to thrive,severe metabolic acidosis, rickets and nephrocalcinosis.Progressive hearing loss may develop in patients withrecessive dRTA, which, depending the causative genemutation, can be present at birth or develop later in adolescence or early adulthood. Diagnosis of dRTA can be challenging, since it requires a high index of suspicion and/or measurement of urinary pH after an acid load, usually in the form of oral ammonium chloride; this should normally acidify the urine to pH below 5.3. In dRTA, urinary citrate levels a real so low and patients are at increased risk of for mingkidney stones from a combination of alkaline urine and low citrate. Ideally, affected patients need regular outpatient follow-up by a urologist and nephrologist. Thus, any patient found to have a calcium phosphate kidney stone, low urinary citrate, and raised urinary pH, especially with an early morning pH >5.5, should be evaluated for underlying dRTA. Patients with complete dRTA will have a low (<20 mmol/L) plasma or serum bicarbonate concentration, whereas in those with incomplete dRTA, bicarbonate levels are usually normal. Oral alkali as potassiumcitrate is still the mainstay of treatment in dRTA.
Topics: Acidosis, Renal Tubular; Adolescent; Adult; Ammonium Chloride; Child; Citric Acid; Humans; Hydrogen-Ion Concentration; Kidney Calculi
PubMed: 33459628
DOI: No ID Found -
Nephrology, Dialysis, Transplantation :... Dec 2021Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of... (Review)
Review
Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.
Topics: Acidosis; Bicarbonates; Cognitive Dysfunction; Humans; Motor Disorders; Renal Insufficiency, Chronic
PubMed: 34718761
DOI: 10.1093/ndt/gfab216 -
The Canadian Veterinary Journal = La... Nov 2023Metabolic acidosis (MA) is the most common acid-base disorder reported in horses with colitis but its association with survival is yet to be determined.
BACKGROUND
Metabolic acidosis (MA) is the most common acid-base disorder reported in horses with colitis but its association with survival is yet to be determined.
OBJECTIVE
Investigate the types of MA in horses with colitis to determine effects of various anions on fatality rates.
ANIMALS AND PROCEDURES
We studied 158 horses with colitis. Horses were classified into 4 groups depending on the anion contributing to MA: i) no MA, ii) lactic acidosis (LA), iii) unmeasured strong ion (USI) acidosis, and iv) hyperchloremic acidosis (HA).
RESULTS
Sixty percent (95/158) of horses had no MA, 22% (34/158) had LA, 12% (19/158) had HA, and 6% (10/158) had USI acidosis. The fatality rate of horses without MA was 20% (20/95), whereas the rates for those with LA, USI, and HA were 53% (18/34), 30% (3/10), and 16% (3/19), respectively. Horses with LA were more likely to die or be euthanized than horses without MA (OR: 4.2, 95% CI: 1.83 to 9.72, < 0.001) and HA (OR: 5.9, 95% CI: 1.47 to 24.4, < 0.01).
CONCLUSION AND CLINICAL RELEVANCE
Lactic acidosis was the most common type of MA in horses with colitis, and it was associated with non-survival.
Topics: Animals; Horses; Acidosis, Lactic; Acidosis; Colitis; Horse Diseases
PubMed: 37915775
DOI: No ID Found