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International Journal of Molecular... Feb 2024Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and... (Review)
Review
Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and plant-sourced food, particularly fruits and vegetables, generally yield bases when metabolized. Modern diets proportionately contain more animal-sourced than plant-sourced foods, are, thereby, generally net acid-producing, and so constitute an ongoing acid challenge. Acid accumulation severe enough to reduce serum bicarbonate concentration, i.e., manifesting as chronic metabolic acidosis, the most extreme end of the continuum of "acid stress", harms bones and muscles and appears to enhance the progression of chronic kidney disease (CKD). Progressive acid accumulation that does not achieve the threshold amount necessary to cause chronic metabolic acidosis also appears to have deleterious effects. Specifically, identifiable acid retention without reduced serum bicarbonate concentration, which, in this review, we will call "covert acidosis", appears to cause kidney injury and exacerbate CKD progression. Furthermore, the chronic engagement of mechanisms to mitigate the ongoing acid challenge of modern diets also appears to threaten health, including kidney health. This review describes the full continuum of "acid stress" to which modern diets contribute and the mechanisms by which acid stress challenges health. Ongoing research will develop clinically useful tools to identify stages of acid stress earlier than metabolic acidosis and determine if dietary acid reduction lowers or eliminates the threats to health that these diets appear to cause.
Topics: Animals; Bicarbonates; Acid-Base Equilibrium; Diet; Acidosis; Renal Insufficiency, Chronic
PubMed: 38397012
DOI: 10.3390/ijms25042336 -
Clinical Journal of the American... Sep 2021
Topics: Acidosis; Fruit; Humans; Renal Dialysis
PubMed: 34497106
DOI: 10.2215/CJN.09610721 -
Immunology Jul 2018Due to imbalances between vascularity and cellular growth patterns, the tumour microenvironment harbours multiple metabolic stressors including hypoxia and acidosis,... (Review)
Review
Due to imbalances between vascularity and cellular growth patterns, the tumour microenvironment harbours multiple metabolic stressors including hypoxia and acidosis, which have significant influences on remodelling both tumour and peritumoral tissues. These stressors are also immunosuppressive and can contribute to escape from immune surveillance. Understanding these effects and characterizing the pathways involved can identify new targets for therapy and may redefine our understanding of traditional anti-tumour therapies. In this review, the effects of hypoxia and acidosis on tumour immunity will be summarized, and how modulating these parameters and their sequelae can be a useful tool for future therapeutic interventions is discussed.
Topics: Acidosis; Animals; Humans; Hypoxia; Immune System; Immune Tolerance; Immunologic Surveillance; Immunotherapy; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 29485185
DOI: 10.1111/imm.12917 -
Biochimica Et Biophysica Acta. Reviews... Apr 2019While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with... (Review)
Review
While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with metabolic re-programming, and there is clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. Notably, many of the metabolic adaptations observed in cancer are similar to the same perturbations observed in diabetic patients. For example, metformin is commonly used to reduce hyperglycemia in diabetic patients, and has been demonstrated to reduce cancer incidence. Treatment with PI3K inhibitors can induce hyperinsulinemia, which can blunt therapeutic efficacy if unchecked. While commonalities between metabolism in cancer and diabetes have been extensively reviewed, here we examine a less explored and emergent convergence between diabetic and cancer metabolism: the generation of lactic acid and subsequent acidification of the surrounding microenvironment. Extracellular lactic acidosis is integral in disease manifestation and is a negative prognostic in both disease states. In tumors, this results in important sequela for cancer progression including increased invasion and metastasis, as well as inhibition of immune surveillance. In diabetes, acidosis impacts the ability of insulin to bind to its receptor, leading to peripheral resistance and an exacerbation of symptoms. Thus, acidosis may be a relevant therapeutic target, and we describe three approaches for targeting: buffers, nanomedicine, and proton pump inhibitors.
Topics: Acidosis, Lactic; Animals; Buffers; Diabetes Mellitus; Humans; Nanomedicine; Neoplasms; Proton Pump Inhibitors
PubMed: 30708040
DOI: 10.1016/j.bbcan.2019.01.003 -
Jornal Brasileiro de Nefrologia 2017Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is associated with increased mortality and its deleterious effects are already present in... (Review)
Review
Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is associated with increased mortality and its deleterious effects are already present in the predialysis phase of chronic kidney disease. Metabolic acidosis has been linked to progression of chronic kidney disease, changes in protein and glucose metabolism, bone and muscle disorders and cardiovascular disease. At present, the control of metabolic acidosis in hemodialysis is mainly focused on the supply of bicarbonate during dialysis session, but further studies are needed to set the optimum target serum bicarbonate and the best concentration of the bicarbonate dialysate. The present study reviews pathophysiological and epidemiological aspects of metabolic acidosis in hemodialysis patients and also addresses its adverse effects and treatment.
Topics: Acidosis; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 29044339
DOI: 10.5935/0101-2800.20170053 -
Journal of the American Society of... Mar 2015Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of... (Review)
Review
Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications.
Topics: Acidosis; Alkalies; Animals; Bicarbonates; Cardiovascular Diseases; Dietary Supplements; Humans; Renal Insufficiency, Chronic
PubMed: 25150154
DOI: 10.1681/ASN.2014020205 -
Nutrients May 2017Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors... (Review)
Review
Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors that may influence the occurrence of such a condition. The excessive consumption of acid precursor foods (sources of phosphorus and proteins), to the detriment of those precursors of bases (sources of potassium, calcium, and magnesium), leads to acid-base balance volubility. If this condition occurs in a prolonged, chronic way, low-grade metabolic acidosis can become significant and predispose to metabolic imbalances such as kidney stone formation, increased bone resorption, reduced bone mineral density, and the loss of muscle mass, as well as the increased risk of chronic diseases such as type 2 diabetes mellitus, hypertension, and non-alcoholic hepatic steatosis. Considering the increase in the number of studies investigating the influence of diet-induced metabolic acidosis on clinical outcomes, this review gathers the available evidence evaluating the association of this disturbance and metabolic imbalances, as well as related mechanisms. It is necessary to look at the western dietary pattern of most countries and the increasing incidence of non-comunicable diseases for the balance between fruit and vegetable intake and the appropriate supply of protein, mainly from animal sources, so that it does not exceed the daily recommendations.
Topics: Acidosis; Diet; Humans; Noncommunicable Diseases
PubMed: 28587067
DOI: 10.3390/nu9060538 -
Journal of the American Society of... Apr 2023Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of...
SIGNIFICANCE STATEMENT
Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted.
BACKGROUND
Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry.
METHODS
The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants.
RESULTS
The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants.
CONCLUSIONS
MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.
Topics: Male; Female; Humans; Chronic Kidney Disease-Mineral and Bone Disorder; Cross-Sectional Studies; Retrospective Studies; Bicarbonates; Bone Density; Radius; Renal Insufficiency, Chronic; Acidosis
PubMed: 36749125
DOI: 10.1681/ASN.0000000000000085 -
Journal of the American Society of... Aug 2017
Topics: Acidosis; Ammonium Compounds; Humans; Hypertension, Renal; Nephritis; Renal Insufficiency, Chronic
PubMed: 28630230
DOI: 10.1681/ASN.2017040470 -
Kidney & Blood Pressure Research 2020Metabolic acidosis may be diagnosed as chronic (cMA) if it persists for at least 5 days, although an exact definition has not been provided by any guidelines yet. The... (Review)
Review
BACKGROUND
Metabolic acidosis may be diagnosed as chronic (cMA) if it persists for at least 5 days, although an exact definition has not been provided by any guidelines yet. The most common cause is CKD; numerous less-known diseases can also account for cMA.
SUMMARY
In recent years, CKD-associated cMA has been proposed to induce several clinical complications. The aim of the article was to assess the current clinical evidence for complications and the respective management of CKD-associated cMA. In summary, cMA in CKD most likely promotes protein degradation and loss of bone mineral density. It aggravates CKD progression as indicated by experimental and (partly) clinical data. Therefore, cMA control must be recommended. Besides oral bicarbonate, dietary interventions potentially offer an alternative. Veverimer is a future option for cMA control; further systematic data are needed.
CONCLUSIONS
The most common cause of cMA is CKD. CKD-associated cMA most likely induces a negative protein balance; the exact role on bone metabolism remains uncertain. It presumably aggravates CKD progression. cMA control is recommendable; the serum bicarbonate target level should range around 24 mEq/L. Veverimer may be established as future option for cMA control; further systematic data are needed.
Topics: Acidosis; Animals; Bicarbonates; Bone Density; Chronic Disease; Diet Therapy; Disease Management; Humans; Polymers; Proteolysis; Renal Insufficiency, Chronic
PubMed: 33264780
DOI: 10.1159/000510829