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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 -
International Journal of Molecular... May 2024Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor... (Review)
Review
Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.
Topics: Humans; Acidosis; Renal Insufficiency, Chronic; Sodium Bicarbonate; Animals; Treatment Outcome
PubMed: 38791238
DOI: 10.3390/ijms25105187 -
Emergency Medicine Clinics of North... May 2022Numerous drugs and toxins can cause metabolic acidosis. The treating clinician should be aware of the many compounds that can produce metabolic acidosis following an... (Review)
Review
Numerous drugs and toxins can cause metabolic acidosis. The treating clinician should be aware of the many compounds that can produce metabolic acidosis following an accidental exposure, an overdose, or with therapeutic use. Awareness and comprehension of those substances associated with metabolic acidosis will facilitate the diagnosis and treatment of poisoned patients.
Topics: Acidosis; Causality; Drug Overdose; Humans; Poisons
PubMed: 35461622
DOI: 10.1016/j.emc.2022.01.002 -
Kidney360 Nov 2021Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical...
BACKGROUND
Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical metabolic acidosis in this population, we examined prospective associations of body mass index (BMI) with elevated anion gap and whether anion gap values in obesity associate with low bicarbonate.
METHODS
Data from adult outpatients (=94,448) in the Bronx, New York were collected from 2010 to 2018. Mixed effects models and Cox proportional hazards models were used to examine associations of BMI with elevated anion gap and anion gap metabolic acidosis and of baseline anion gap with incident low bicarbonate and anion gap metabolic acidosis. Anion gap was defined using traditional and albumin-corrected calculations.
RESULTS
Greater BMI was associated with higher anion gap over time and with progressively greater risk of developing an elevated anion gap (hazard ratio [HR] for body mass index [BMI]≥40 kg/m versus 18 to <25 kg/m, 1.32; 95% confidence interval [95% CI], 1.23 to 1.42 for traditional and HR for BMI≥40 kg/m versus 18 to <25 kg/m, 1.74; 95% CI, 1.63 to 1.85 for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI≥40 kg/m, 1.53; 95% CI, 1.39 to 1.69). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HR for fourth versus first quartile, 1.29; 95% CI, 1.23 to 1.44 for traditional and HR for fourth versus first quartile, 1.36; 95% CI, 1.26 to 1.48 for corrected) and higher risk of anion gap metabolic acidosis (HR for fourth versus first quartile, 1.78; 95% CI, 1.59 to 1.99).
CONCLUSIONS
Obesity is characterized by unmeasured anion accumulation and acid retention or overproduction. Modest elevations in anion gap among patients with obesity are associated with previously unrecognized anion gap metabolic acidosis.
Topics: Acid-Base Equilibrium; Acidosis; Adult; Bicarbonates; Cohort Studies; Humans; Obesity
PubMed: 35372994
DOI: 10.34067/KID.0003562021 -
Pediatric Nephrology (Berlin, Germany) Dec 2023Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized...
BACKGROUND
Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs.
METHODS
Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics.
RESULTS
Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03-0.3) and 0.24 mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis.
CONCLUSIONS
Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Kidney Transplantation; Bicarbonates; Acidosis; Renal Insufficiency, Chronic; Transplant Recipients; Alkalies
PubMed: 37422606
DOI: 10.1007/s00467-023-06072-z -
The American Journal of Emergency... Oct 2023Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality. (Review)
Review
INTRODUCTION
Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality.
OBJECTIVE
This review highlights the pearls and pitfalls of metformin toxicity, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence.
DISCUSSION
Metformin is a common medication used for treatment of diabetes mellitus. Metformin toxicity is a spectrum of conditions that may be differentiated into three subgroups: metformin-associated lactic acidosis (MALA), metformin-induced lactic acidosis (MILA), and metformin-unrelated lactic acidosis (MULA). MILA is a condition found predominantly in patients chronically taking metformin or those with large acute overdoses. Conversely, MULA occurs in patients on metformin but with a critical illness stemming from a separate cause. MALA is rare but the most severe form, with mortality rates that reach 50%. Differentiating these entities is difficult in the ED setting without obtaining metformin levels. Patients with metformin toxicity present with nonspecific gastrointestinal symptoms and vital sign abnormalities. Laboratory analysis will reveal a high lactate with anion gap metabolic acidosis. Patients presenting with elevated lactate levels in the setting of metformin use should be considered at risk for the most severe form, MALA. Patients with MALA require aggressive treatment with intravenous fluids, treatment of any concomitant condition, and early consideration of hemodialysis, along with specialist consultation such as nephrology and toxicology.
CONCLUSIONS
An understanding of metformin toxicity can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
Topics: Humans; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Acidosis, Lactic; Prevalence; Lactic Acid
PubMed: 37517113
DOI: 10.1016/j.ajem.2023.07.020 -
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 -
The Journal of Surgical Research Oct 2023Very low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an... (Clinical Trial)
Clinical Trial
INTRODUCTION
Very low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance.
MATERIALS AND METHODS
Twenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005.
CLINICALTRIALS
gov ID: NCT05442918.
RESULTS
Patients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1.
CONCLUSIONS
Preoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.
Topics: Humans; Acidosis; Caloric Restriction; Diabetes Mellitus, Type 2; Ketones; Ketosis; Obesity
PubMed: 37271067
DOI: 10.1016/j.jss.2023.05.001 -
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