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Nutrients Oct 2020Hemodialysis (HD) majorly represents the global treatment option for patients with chronic kidney disease stage 5, and, despite advances in dialysis technology, these... (Review)
Review
Hemodialysis (HD) majorly represents the global treatment option for patients with chronic kidney disease stage 5, and, despite advances in dialysis technology, these patients face a high risk of morbidity and mortality from malnutrition. We aimed to provide a novel view that malnutrition susceptibility in the global HD community is either or both of iatrogenic and of non-iatrogenic origins. This categorization of malnutrition origin clearly describes the role of each factor in contributing to malnutrition. Low dialysis adequacy resulting in uremia and metabolic acidosis and dialysis membranes and techniques, which incur greater amino-acid losses, are identified modifiable iatrogenic factors of malnutrition. Dietary inadequacy as per suboptimal energy and protein intakes due to poor appetite status, low diet quality, high diet monotony index, and/or psychosocial and financial barriers are modifiable non-iatrogenic factors implicated in malnutrition in these patients. These factors should be included in a comprehensive nutritional assessment for malnutrition risk. Leveraging the point of origin of malnutrition in dialysis patients is crucial for healthcare practitioners to enable personalized patient care, as well as determine country-specific malnutrition treatment strategies.
Topics: Acidosis; Dietary Proteins; Eating; Energy Intake; Female; Humans; Male; Malnutrition; Nutrition Assessment; Nutritional Physiological Phenomena; Renal Dialysis; Renal Insufficiency, Chronic; Uremia
PubMed: 33076282
DOI: 10.3390/nu12103147 -
JAMA Network Open Nov 2020Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
IMPORTANCE
Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline.
OBJECTIVE
To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA.
DESIGN, SETTING, AND PARTICIPANTS
This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020.
INTERVENTIONS
Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule.
MAIN OUTCOMES AND MEASURES
The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion.
RESULTS
Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03).
CONCLUSIONS AND RELEVANCE
In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.
Topics: Acidosis; Adult; Cluster Analysis; Cross-Over Studies; Crystalloid Solutions; Diabetic Ketoacidosis; Electrolytes; Emergency Service, Hospital; Female; Fluid Therapy; Humans; Infusions, Intravenous; Insulin; Intensive Care Units; Isotonic Solutions; Male; Middle Aged; Outcome Assessment, Health Care; Saline Solution, Hypertonic; Time Factors
PubMed: 33196806
DOI: 10.1001/jamanetworkopen.2020.24596 -
Journal of Nephrology Dec 2021Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO is impaired, leading to chronic metabolic... (Review)
Review
Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO is impaired, leading to chronic metabolic acidosis with normal anion gap. In the current review, the focus is placed on the most common type of RTA, Type 1 RTA or Distal RTA (dRTA), which is a rare chronic genetic disorder characterized by an inability of the distal nephron to secrete hydrogen ions in the presence of metabolic acidosis. Over the years, knowledge of the molecular mechanisms behind acid secretion has improved, thereby greatly helping the diagnosis of dRTA. The primary or inherited form of dRTA is mostly diagnosed in infancy, childhood, or young adulthood, while the acquired secondary form, as a consequence of other disorders or medications, can happen at any age, although it is more commonly seen in adults. dRTA is not as "benign" as previously assumed, and can have several, highly variable long-term consequences. The present review indeed reports and summarizes both clinical symptoms and diagnosis, long-term outcomes, genetic inheritance, epidemiology and current treatment options, with the aim of shedding more light onto this rare disorder. Being a chronic condition, dRTA also deserves attention in the transition between pediatric and adult nephrology care, and as a rare disease it has a place in the European and Italian rare nephrological diseases network.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Biological Transport; Child; Humans; Young Adult
PubMed: 33770395
DOI: 10.1007/s40620-021-01032-y -
BioMed Research International 2020Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some... (Review)
Review
Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.
Topics: Acidosis; Animals; Humans; Lactic Acid; Metabolic Networks and Pathways; Metabolome
PubMed: 32685468
DOI: 10.1155/2020/3419034 -
Journal of the American Society of... Feb 2021The kidney plays an important role in maintaining normal blood pH. Metabolic acidosis (MA) upregulates the pathway that mitochondria in the proximal tubule (PT) use to...
BACKGROUND
The kidney plays an important role in maintaining normal blood pH. Metabolic acidosis (MA) upregulates the pathway that mitochondria in the proximal tubule (PT) use to produce ammonia and bicarbonate from glutamine, and is associated with AKI. However, the extent to which MA causes AKI, and thus whether treating MA would be beneficial, is unclear.
METHODS
Gavage with ammonium chloride induced acute MA. Multiphoton imaging of mitochondria (NADH/membrane potential) and transport function (dextran/albumin uptake), oxygen consumption rate (OCR) measurements in isolated tubules, histologic analysis, and electron microscopy in fixed tissue, and urinary biomarkers (KIM-1/clara cell 16) assessed tubular cell structure and function in mouse kidney cortex.
RESULTS
MA induces an acute change in NAD redox state (toward oxidation) in PT mitochondria, without changing the mitochondrial energization state. This change is associated with a switch toward complex I activity and decreased maximal OCR, and a major alteration in normal lipid metabolism, resulting in marked lipid accumulation in PTs and the formation of large multilamellar bodies. These changes, in turn, lead to acute tubular damage and a severe defect in solute uptake. Increasing blood pH with intravenous bicarbonate substantially improves tubular function, whereas preinjection with the NAD precursor nicotinamide (NAM) is highly protective.
CONCLUSIONS
MA induces AKI changes in PT NAD and lipid metabolism, which can be reversed or prevented by treatment strategies that are viable in humans. These findings might also help to explain why MA accelerates decline in function in CKD.
Topics: Acidosis; Acute Kidney Injury; Animals; Disease Models, Animal; Kidney Cortex; Kidney Tubules; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondria; NAD; Oxygen Consumption
PubMed: 33478973
DOI: 10.1681/ASN.2020071003 -
Journal of Nephrology Dec 2019Metabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Metabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear.
METHODS
We conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov ) to determine the effect in patients with CKD stage 3-5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes.
RESULTS
A total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p < 0.001). Similarly, 71 participants [45 (12.3%) in SC and 26 (6.9%) in SB, p = 0.016] started dialysis while 37 participants [25 (6.8%) in SC and 12 (3.1%) in SB, p = 0.004] died. There were no significant effect of SB on blood pressure, total body weight or hospitalizations.
CONCLUSION
In persons with CKD 3-5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.
Topics: Acidosis; Aged; Disease Progression; Female; Glomerular Filtration Rate; Humans; Italy; Kidney; Male; Renal Insufficiency, Chronic; Sodium Bicarbonate; Survival Rate
PubMed: 31598912
DOI: 10.1007/s40620-019-00656-5 -
American Journal of Respiratory and... Sep 2019Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant... (Randomized Controlled Trial)
Randomized Controlled Trial
Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy. To understand the relationship among central venous oxygen saturation (Scv), lactate, and base excess to better determine the origin of lactate. This was a analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of Scv. We defined the "alactic base excess," as the sum of lactate and standard base excess. Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. Scv was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of Scv. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance. Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.
Topics: Acidosis, Lactic; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Fluid Therapy; Humans; Italy; Male; Middle Aged; Oxygen Consumption; Sepsis
PubMed: 30985210
DOI: 10.1164/rccm.201812-2342OC -
Ugeskrift For Laeger Aug 2021It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and... (Review)
Review
It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and functions to dampen reductions in intracellular pH through lactate-H+ cotransport to the extracellular space. Though this may give rise to elevated blood lactate, increased lactate production is not the cause of metabolic acidosis in such instances. "Lactic acidosis" is thus an inappropriate term as it indicates causality and in this review, we suggest that in the future, the term "hyperlactataemia-associated metabolic acidosis" should be used instead.
Topics: Acidosis; Acidosis, Lactic; Humans; Lactic Acid
PubMed: 34477100
DOI: No ID Found -
Nutrients Feb 2023Dietary protein restriction has long been a cornerstone of nutritional therapy for patients with chronic kidney diseases (CKD). However, the recommended amount of... (Review)
Review
Dietary protein restriction has long been a cornerstone of nutritional therapy for patients with chronic kidney diseases (CKD). However, the recommended amount of dietary protein intake is different across guidelines. This is partly because previous randomized controlled trials have reported conflicting results regarding the efficacy of protein restriction in terms of kidney outcomes. Interestingly, a vegetarian, very low protein diet has been shown to reduce the risk of kidney failure among patients with advanced CKD, without increasing the incidence of hyperkalemia. This finding suggests that the source of protein may also influence the kidney outcomes. Furthermore, a plant-dominant low-protein diet (PLADO) has recently been proposed as an alternative dietary therapy for patients with CKD. There are several potential mechanisms by which plant-based diets would benefit patients with CKD. For example, plant-based diets may reduce the production of gut-derived uremic toxins by increasing the intake of fiber, and are useful for correcting metabolic acidosis and hyperphosphatemia. Plant proteins are less likely to induce glomerular hyperfiltration than animal proteins. Furthermore, plant-based diets increase magnesium intake, which may prevent vascular calcification. More evidence is needed to establish the efficacy, safety, and feasibility of PLADO as a new adjunct therapy in real-world patients with CKD.
Topics: Animals; Diet, Protein-Restricted; Dietary Proteins; Renal Insufficiency, Chronic; Kidney; Acidosis
PubMed: 36839360
DOI: 10.3390/nu15041002 -
Clinical Journal of the American... Aug 2021Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury.... (Review)
Review
Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.
Topics: Acid-Base Equilibrium; Acidosis; Acids; Bicarbonates; Chronic Disease; Diet; Glomerular Filtration Rate; Humans; Kidney Diseases; Stress, Physiological
PubMed: 33741720
DOI: 10.2215/CJN.17541120