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Physiological Reports Sep 2022Acute pyelonephritis caused by uropathogenic E. coli (UPEC) can cause renal scarring and lead to development of chronic kidney disease. Prevention of kidney injury...
Acute pyelonephritis caused by uropathogenic E. coli (UPEC) can cause renal scarring and lead to development of chronic kidney disease. Prevention of kidney injury requires an understanding of host factors and/or UPEC adaptive responses that are permissive for UPEC colonization of the urinary tract. Although some studies have suggested urine acidification limits UPEC growth in culture, other studies have described acid-resistance mechanisms (AR) in E. coli such as the CadC/CadBA module that promotes adaptation to acid and nitrosative stress. Herein we confirm and extend our previous study by demonstrating that despite urine acidification, metabolic acidosis induced by dietary ammonium chloride (NH Cl-A) exacerbates cystitis and pyelonephritis in innate immune competent (C3H-HeN) mice characterized by: (1) markedly elevated UPEC burden and increased chemokine/cytokine and NOS2 mRNA expression, (2) accumulation of intravesicular debris noninvasively detected by Power Doppler Ultrasound (PDUS), and (3) collecting duct (CD) dysfunction that manifests as a urine concentration defect. Bladder debris and CD dysfunction were due to the inflammatory response, as neither was observed in Tlr4-deficient (C3H-HeJ) mice. The effect of NH Cl-A was unrelated to acidosis as dietary administration of hydrochloric acid (HCl-A) yielded a comparable acid-base status yet did not increase UPEC burden. NH Cl-A increased polyamines and decreased nitric oxide (NO) metabolites in urine indicating that excess dietary ammonium shifts arginine metabolism toward polyamines at the expense of NO synthesis. Furthermore, despite increased expression of NOS2, NO production post UPEC infection was attenuated in NH Cl-A mice compared to controls. Thus, in addition to induction of metabolic acidosis and urine acidification, excess dietary ammonium alters the polyamine:NO balance and thereby compromises NOS2-mediated innate immune defense.
Topics: Acidosis; Ammonium Chloride; Animals; Arginine; Chemokines; Cystitis; Cytokines; Escherichia coli Infections; Hydrochloric Acid; Mice; Mice, Inbred C3H; Nitric Oxide; Polyamines; Pyelonephritis; RNA, Messenger; Toll-Like Receptor 4; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 36151614
DOI: 10.14814/phy2.15471 -
Chronic Sub-Clinical Systemic Metabolic Acidosis - A Review with Implications for Clinical Practice.Journal of Evidence-based Integrative... 2022When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this... (Review)
Review
When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this review as chronic, sub-clinical, systemic metabolic acidosis (CSSMA). This narrative review explores the scientific basis for CSSMA, its consequences for health, and potential therapeutic interventions. The major etiology of CSSMA is the shift away from the ancestral, alkaline diet which was rich in fruit and vegetables, toward the contemporary, acidogenic 'Westernized' diet characterized by higher animal protein consumption and lack of base forming minerals. Urine pH is reduced with high dietary acid load and may be a convenient marker of CSSMA. Evidence suggests further that CSSMA negatively influences cortisol levels potentially contributing significantly to the pathophysiology thereof. Both CSSMA and high dietary acid load are associated with the risk and prognosis of various chronic diseases. Clinical trials show that CSSMA can be addressed successfully through alkalizing the diet by increasing fruit and vegetable intake and/or supplementing with alkaline minerals. This review confirms the existence of a significant body of evidence regarding this low-grade form of acidosis as well as evidence to support its diverse negative implications for health, and concludes that CSSMA is a condition warranting further research.
Topics: Animals; Acidosis; Water-Electrolyte Imbalance; Graft vs Host Disease; Immunotherapy; Vegetables
PubMed: 36448194
DOI: 10.1177/2515690X221142352 -
Animal : An International Journal of... Jul 2019The increasing lactational performance of dairy cows over the last few decades is closely related to higher nutritional requirements. The decrease in dry matter intake... (Review)
Review
The increasing lactational performance of dairy cows over the last few decades is closely related to higher nutritional requirements. The decrease in dry matter intake during the peripartal period results in a considerable mobilisation of body tissues (mainly fat reserves and muscle mass) to compensate for the prevailing lack of energy and nutrients. Despite the activation of adaptive mechanisms to mobilise nutrients from body tissues for maintenance and milk production, the increased metabolic load is still a risk factor for animal health. The prevalence of production diseases, particularly subclinical ketosis is high in the early lactation period. Increased β-hydroxybutyrate (BHB) concentrations further depress gluconeogenesis, feed intake and the immune system. Despite a variety of adaptation responses to nutrient and energy deficit that exists among dairy cows, an early and non-invasive detection of developing metabolic disorders in milk samples would be useful. The frequent and regular milking process of dairy cows creates the ability to obtain samples at any stage of lactation. Routine identification of biomarkers accurately characterising the physiological status of an animal is crucial for decisive strategies. The present overview recapitulates established markers measured in milk that are associated with metabolic health of dairy cows. Specifically, measurements of milk fat, protein, lactose and urea concentrations are evaluated. Changes in the ratio of milk fat to protein may indicate an increased risk for rumen acidosis and ketosis. The costly determination of individual fatty acids in milk creates barriers for grouping of fatty acids into saturated, mono- and polyunsaturated fatty acids. Novel approaches include the potential of mid-IR (MIR) based predictions of BHB and acetone in milk, although the latter are not directly measured, but only estimated via indirect associations of concomitantly altered milk composition during (sub)clinical ketosis. Although MIR-based ketone body concentrations in milk are not suitable to monitor the metabolic status of the individual cow, they provide an estimate of the overall herd or specific groups of animals earlier in a particular stage of lactation. Management decisions can be made earlier and animal health status improved by adjusting diet composition.
Topics: 3-Hydroxybutyric Acid; Acidosis; Animals; Biomarkers; Cattle; Cattle Diseases; Diet; Fatty Acids; Female; Ketosis; Lactation; Metabolic Diseases; Milk; Nutritional Requirements; Rumen
PubMed: 31280745
DOI: 10.1017/S175173111800349X -
PloS One 2017It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be... (Observational Study)
Observational Study
BACKGROUND
It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN) on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN.
METHODS
This observational study described the acid-base profile of very preterm infants (≤29 week's gestation) receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3) nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate). The outcome measure to assess metabolic acidosis was the base excess (BE).
RESULTS
161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d) and lipids (2.8 ± 1.4 g/kg/d) during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3); -6.4 ± 3.4 (group 2); -5.1 ± 3.0 (group 1)]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes.
DISCUSSION
Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation) displayed greater acidotic disequilibrium and a higher need of bicarbonate.
Topics: Acid-Base Equilibrium; Acidosis; Amino Acids; Gestational Age; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Premature; Lipids; Multivariate Analysis; Parenteral Nutrition
PubMed: 29176758
DOI: 10.1371/journal.pone.0186936 -
PloS One 2023Bone disease is highly prevalent in patients with chronic kidney disease (CKD), leading to an increased risk of bone fractures. This is due in part to metabolic...
Bone disease is highly prevalent in patients with chronic kidney disease (CKD), leading to an increased risk of bone fractures. This is due in part to metabolic acid-induced bone dissolution. Bisphosphonates (BPPs) are a potential treatment for inhibiting bone dissolution; however, there are limited studies observing the use of BPPs on acidotic patients. We aimed to determine efficacy of BPPs on maintaining bone health and pH regulation in acid-exposed mice. Using a diet-induced murine model of metabolic acidosis, we examined bone structure, composition, and mechanics as well as blood gases for three groups: control, acidosis, and acidosis + bisphosphonates (acidosis+BPP). Acidosis was induced for 14 days and alendronate was administered every 3 days for the acidosis+BPP group. The administration of BPP had little to no effect on bone structure, mechanics, and composition of the acidosis bones. However, administration of BPP did cause the mice to develop more severe acidosis than the acidosis only group. Overall, we discovered that BPPs may exacerbate acidosis symptoms by inhibiting the release of buffering ions from bone. Therefore, we propose that BPP administration should be carefully considered for those with CKD and that alkali supplementation could help minimize acidifying effects.
Topics: Animals; Mice; Alendronate; Ammonium Chloride; Diphosphonates; Acidosis; Osteolysis; Renal Insufficiency, Chronic
PubMed: 37713420
DOI: 10.1371/journal.pone.0291649 -
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 -
Polish Archives of Internal Medicine Oct 2018Introduction Metabolic acidosis (MA) may accelerate the progression of chronic kidney disease (CKD) and is an important risk factor for increased mortality in CKD...
Introduction Metabolic acidosis (MA) may accelerate the progression of chronic kidney disease (CKD) and is an important risk factor for increased mortality in CKD patients. The clinical value of MA in kidney transplant (KTx) recipients has not been extensively studied so far. Objectives The aim of this clinical single‑‑center case‑‑control study was to assess the prevalence of MA in KTx recipients in comparison with CKD patients and to identify pathogenic factors for MA in KTx recipients. Patients and methods Venous blood concentrations of bicarbonate (HCO3-) and blood hemoglobin concentrations were measured in 500 KTx recipients and 500 CKD patients matched for sex, age, and estimated glomerular filtration rate (eGFR). None of these patients received alkali treatment before the study. MA was diagnosed in KTx recipients with HCO3- levels lower than 22 mmol/l. Results The prevalence of MA was lower in KTx recipients than in CKD patients (12.0% vs 19.6%; P = 0.001). In both groups, the prevalence increased with progression of CKD stages (P <0.001 for trend) and was higher in patients with anemia. In a multivariable analysis, hemoglobin concentrations correlated independently with eGFR and HCO3- in KTx recipients (β = 0.314, P <0.001 and β = 0.274, P <0.001, respectively). Similar correlations were observed in CKD patients (β = 0.273, P <0.001 and β = 0.123, P = 0.006, respectively). Conclusions Our study revealed that the prevalence of MA is lower in KTx recipients than in CKD patients. Moreover, in KTx recipients, blood bicarbonate concentrations are related to kidney function and blood hemoglobin concentrations.
Topics: Acidosis; Adult; Bicarbonates; Case-Control Studies; Female; Humans; Kidney Transplantation; Male; Middle Aged; Prevalence; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 30207550
DOI: 10.20452/pamw.4329 -
Nutrients Feb 2022Increased dietary acid load has a negative impact on health, particularly when renal function is compromised. Fibroblast growth factor 23 (FGF23) is a bone-derived...
Increased dietary acid load has a negative impact on health, particularly when renal function is compromised. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that is elevated during renal failure. The relationship between metabolic acidosis and FGF23 remains unclear. To investigate the effect of dietary acid load on circulating levels of FGF23, rats with normal renal function and with a graded reduction in renal mass (1/2 Nx and 5/6 Nx) received oral NH4Cl for 1 month. Acid intake resulted in a consistent decrease of plasma FGF23 concentrations in all study groups when compared with their non-acidotic control: 239.3 ± 13.5 vs. 295.0 ± 15.8 pg/mL (intact), 346.4 ± 19.7 vs. 522.6 ± 29.3 pg/mL (1/2 Nx) and 988.0 ± 125.5 vs. 2549.4 ± 469.7 pg/mL (5/6 Nx). Acidosis also decreased plasma PTH in all groups, 96.5 ± 22.3 vs. 107.3 ± 19.1 pg/mL, 113.1 ± 17.3 vs. 185.8 ± 22.2 pg/mL and 504.9 ± 75.7 vs. 1255.4 ± 181.1 pg/mL. FGF23 showed a strong positive correlation with PTH (r = 0.877, p < 0.0001) and further studies demonstrated that acidosis did not influence plasma FGF23 concentrations in parathyroidectomized rats, 190.0 ± 31.6 vs. 215 ± 25.6 pg/mL. In conclusion, plasma concentrations of FGF23 are consistently decreased in rats with metabolic acidosis secondary to increased acid intake, both in animals with intact renal function and with decreased renal function. The in vivo effect of metabolic acidosis on FGF23 appears to be related to the simultaneous decrease in PTH.
Topics: Acidosis; Animals; Bone and Bones; Calcium; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Rats
PubMed: 35268016
DOI: 10.3390/nu14051041 -
The Turkish Journal of Gastroenterology... Oct 2019Metabolic acidosis is a common complication in patients with cirrhosis at the intensive care units (ICUs) and associated with increased mortality. The aim of our...
BACKGROUND/AIMS
Metabolic acidosis is a common complication in patients with cirrhosis at the intensive care units (ICUs) and associated with increased mortality. The aim of our research was to explore the epidemiology and risk factors of metabolic acidosis in critically ill patients with cirrhosis.
MATERIALS AND METHODS
A total of 975 patients with cirrhosis were selected into our study, and all participants were followed up for at least 28 days. Cox regression model and machine-learning algorithm were used to identify the importance of different risk factors, respectively. Finally, an improved prognostic model as Model for End-stage Liver Disease and metabolic acidosis (MELD-MA) was developed.
RESULTS
Among the 975 patients with liver cirrhosis, 506 had metabolic acidosis, including 257 patients who had decompensated metabolic acidosis at ICU admission. The 28-day mortality was 41% (206/506) in patients with metabolic acidosis. Bilirubin (hazard ratio (HR): 1.023, 95% confidence interval (CI): 1.011-1.036), international normalized ratio (HR: 1.527, 95% CI: 1.332-1.750), pH (HR: 0.173, 95% CI: 0.047-0.640), BE-Lac (HR: 0.907, 95% CI: 0.868-0.948), and BE-Na (HR: 0.923, 95% CI: 0.859-0.991) were considered as independent prognostic parameters for 28-day mortality. MELD-NA had significantly higher discrimination (area under the receiver operating characteristic curve 0.79) than MELD and Child-Pugh score.
CONCLUSION
Critically ill patients with cirrhosis have a high mortality rate and poor prognosis because of the high prevalence of metabolic acidosis. Lactic acidosis is the worst prognosis of all types of metabolic acidosis. MELD-MA performs well on the short-term mortality assessment in critically ill patients with cirrhosis and metabolic acidosis.
Topics: Acidosis; Aged; Critical Illness; Female; Humans; Intensive Care Units; Liver Cirrhosis; Male; Middle Aged; Prognosis; Proportional Hazards Models; Risk Factors; Severity of Illness Index
PubMed: 31633484
DOI: 10.5152/tjg.2019.18813 -
Experimental Physiology Sep 2018What is the topic of this review? The aim of this review is to discuss the potential involvement of exercise-induced acidosis in the commonly reported complications in... (Review)
Review
NEW FINDINGS
What is the topic of this review? The aim of this review is to discuss the potential involvement of exercise-induced acidosis in the commonly reported complications in sickle cell disease. What advances does it highlight? Blood acidosis appears clearly to be a risk factor for HbS polymerization, red blood cell sickling and the occurrence of vaso-occlusive crisis and could induce hyperkalaemia-related complications. It could be of great interest to try to avoid blood acidosis during exercise, which could be done using some alkalinizing solutions or adapted endurance training interventions.
ABSTRACT
Sickle cell disease (SCD) is an inherited haemoglobin (Hb) disorder and the most common monogenic disease in the world. The root cause of this pathology is the synthesis of an abnormal Hb (HbS) that polymerizes in deoxygenated conditions, leading to the sickling of red blood cells. Acidosis is well recognized as a promoter of HbS polymerization and therefore red blood cell sickling. Indeed, it has been shown in vitro that the relative amount of sickled red blood cells increases markedly from 1% at pH 7.4 to >90% at pH 7.0. Nevertheless, no study has directly tested whether exercise-induced acidosis could favour SCD complications. Greater knowledge of the effects of metabolic acidosis during exercise could be of importance given the conclusions reached in several studies that proposed regular physical exercise as a therapeutic strategy in the management of SCD. In this review, we discuss the potential consequences of exercise-induced acidosis for the pathophysiology of SCD. We also propose some potential therapeutic interventions with the aim of reducing the metabolic acidosis related to exercise.
Topics: Acidosis; Anemia, Sickle Cell; Erythrocytes, Abnormal; Exercise; Humans
PubMed: 30024072
DOI: 10.1113/EP087169