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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 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 -
Advances in Therapy Oct 2021Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD...
INTRODUCTION
Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence.
METHODS
Adult patients with CKD stage 3-5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate < 18 mEq/l and < 22 mEq/l).
RESULTS
In the 2017 patient cohort and among patients with CKD and hyperkalemia, patients with metabolic acidosis were younger (69 versus 74 years), more likely to have advanced CKD (35% versus 13%), and use oral sodium bicarbonate (21% versus 4%) than patients without metabolic acidosis. The prevalence of metabolic acidosis (< 22 mEq/l) ranged from 25 to 29% when hyperkalemia was defined by potassium > 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l.
CONCLUSION
Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.
Topics: Acidosis; Humans; Hyperkalemia; Potassium; Prevalence; Renal Insufficiency, Chronic
PubMed: 34471991
DOI: 10.1007/s12325-021-01886-5 -
Kidney360 Apr 2022People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual...
BACKGROUND
People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD.
METHODS
This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or S-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or S-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models.
RESULTS
Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m, respectively) and moderate (52 and 102 ml/min per 1.73 m, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m).
CONCLUSIONS
We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.
Topics: Acidosis; Anemia, Sickle Cell; Creatinine; Cross-Sectional Studies; Glomerular Filtration Rate; Humans; Hyperkalemia; Nutrition Surveys
PubMed: 35721605
DOI: 10.34067/KID.0006802021 -
Nephron 2023Serum creatinine and albuminuria are primary markers of glomerular function and injury, respectively. Tubular secretion, acid-base homeostasis, protein reabsorption,... (Review)
Review
BACKGROUND
Serum creatinine and albuminuria are primary markers of glomerular function and injury, respectively. Tubular secretion, acid-base homeostasis, protein reabsorption, among other tubular functions, are largely ignored. This mini-review aimed to discuss how two tubular functions, secretion, and acid-base homeostasis are associated with major adverse kidney events (MAKEs).
SUMMARY
Proximal tubular secretion is an essential function that allows the elimination of endogenous substances and drugs. Recently discovered endogenous markers in urine and plasma allow a noninvasive way of assessing tubular secretion markers. Several studies have found an association between these markers and a higher risk of chronic kidney disease (CKD) progression and mortality. In a study we recently performed among patients with CKD and at risk of cardiovascular events, lower tubular secretion was associated with an increased risk of acute kidney injury and metabolic acidosis, independent of baseline eGFR and albuminuria. The kidney tubules also play a crucial role in acid-base homeostasis. Although the standard clinical assessment of acidosis consists of measuring serum bicarbonate, urinary ammonium excretion decreases before over metabolic acidosis. Urinary ammonium excretion is associated with CKD progression, a higher risk of kidney failure, and an increased mortality risk, independent of baseline eGFR and albuminuria.
KEY MESSAGES
Novel biomarkers of kidney tubular health consistently associate with MAKEs, above and beyond baseline eGFR, albuminuria, and other CKD risk factors. Tubular markers may provide new opportunities to improve kidney prognosis, drug dosing, and monitoring for adverse events.
Topics: Humans; Albuminuria; Kidney Tubules; Renal Insufficiency, Chronic; Biomarkers; Acidosis; Ammonium Compounds; Glomerular Filtration Rate
PubMed: 37524063
DOI: 10.1159/000531946 -
Kidney360 Apr 2022
Topics: Acidosis; Alkalies; Child; Humans; Renal Insufficiency, Chronic
PubMed: 35721614
DOI: 10.34067/KID.0000072022 -
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