Correction Of Metabolic Acidosis Research Articles

Six pills less: no benefit for bicarbonate supplementation in renal allograft recipients

Metabolic acidosis (defined as serum bicarbonate <22 mmol/L) is frequent in patients with chronic kidney disease and is associated with disease progression. 1 Chapter 3: management of progression and complications of CKD. Kidney Int Suppl (2011). 2013; 3 (No authors listed): 73-90 Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar Several prospective trials and meta-analyses 2 Hultin S Hood C Campbell KL Toussaint ND Johnson DW Badve SV A systematic review and meta-analysis on effects of bicarbonate therapy on kidney outcomes. Kidney Int Rep. 2020; 6: 695-705 Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar , 3 Witham MD Band M Chong H et al. Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. Health Technol Assess. 2020; 24: 1-90 Crossref PubMed Scopus (8) Google Scholar , 4 Di Iorio BR Bellasi A Raphael KL et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI study. J Nephrol. 2019; 32: 989-1001 Crossref PubMed Scopus (70) Google Scholar , 5 Dubey AK Sahoo J Vairappan B Haridasan S Parameswaran S Priyamvada PS Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial. Nephrol Dial Transplant. 2020; 35: 121-129 PubMed Google Scholar , 6 Navaneethan SD Shao J Buysse J Bushinsky DA Effects of treatment of metabolic acidosis in CKD: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2019; 14: 1011-1020 Crossref PubMed Scopus (60) Google Scholar have suggested potential positive effects (of low certainty) of sodium bicarbonate treatment on chronic kidney disease progression, and bicarbonate supplementation is recommended in patients with chronic kidney disease with serum bicarbonate less than 22 mmol/L. 1 Chapter 3: management of progression and complications of CKD. Kidney Int Suppl (2011). 2013; 3 (No authors listed): 73-90 Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar However, protective mechanisms are not fully understood and it is difficult to determine whether acidosis is a cause or consequence of renal function decline. Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trialIn adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Full-Text PDF

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Swiss National Science Foundation.

Uremic Encephalopathy.

HomeRadiologyVol. 307, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyUremic EncephalopathyDavid A. Lizarazo , Jairo LizarazoDavid A. Lizarazo , Jairo LizarazoAuthor AffiliationsFrom the Department of Diagnostic Imaging, Fundación Santa Fe de Bogotá, Universidad El Bosque, Ave 116 No. 9-02, Bogotá 110246, Colombia (D.A.L.); and Department of Internal Medicine, Hospital Universitario Erasmo Meoz, Universidad de Pamplona, Cúcuta, Colombia (J.L.).Address correspondence to D.A.L. (email: [email protected]).David A. Lizarazo Jairo LizarazoPublished Online:Dec 20 2022https://doi.org/10.1148/radiol.221602MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 54-year-old man was admitted for a 3-day history of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. His past medical history included diabetes mellitus and end-stage renal disease on hemodialysis. On admission, there were elevated blood urea nitrogen and creatinine levels with a metabolic acidosis. Axial CT scan of the brain showed symmetrical hypoattenuation of both basal ganglia (Figure). Noncontrast brain T2-weighted MRI demonstrated symmetrical high signal intensity in the basal ganglia surrounded by a more hyperintense rim delineating the lentiform nucleus (Figure). This is the lentiform fork sign, wherein the internal and external capsules and the medullary laminae become hyperintense with axial T2-weighted images (Figure). After correction of the metabolic acidosis with prompt dialysis and glycemic control, the neurologic examination returned to normal, and his symptoms completely resolved. A follow-up MRI examination was not performed.Images in a 54-year-old man who presented with a 3-day evolution of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. He had diabetes mellitus and end-stage renal disease and was undergoing hemodialysis. Laboratory tests showed azotemia and metabolic acidosis. (A) Axial CT scan of brain shows symmetrical hypoattenuation in the bilateral basal ganglia. (B) Axial T2-weighted fluid-attenuated inversion recovery noncontrast brain MRI scan demonstrates bilateral symmetrical swollen lentiform nuclei with a hyperintense rim delineating the lentiform nucleus with a typical fork-like appearance representing the “lentiform fork sign.” (C) Schematic drawing shows the “lentiform fork sign.” At follow-up after correction of metabolic acidosis with prompt dialysis and glycaemic control, the neurologic examination was normal, and symptoms completely resolved. Follow-up scan was not performed. EC = external capsule, IC = internal capsule, LME = external medullary lamina, LMI = internal medullary lamina, TS = the stem.Download as PowerPointOpen in Image Viewer Uremic encephalopathy is a neurologic complication resulting from endogenous uremic toxins in patients with severe renal failure. The pathogenesis is complex and unclear (1). The lentiform fork sign (Figure) is attributed to metabolic acidosis in patients with diabetes and renal failure with a history of incomplete dialysis leading to reversible basal ganglia and adjacent white matter injury (2). The edematous external capsule represents the lateral arm of the fork, with both the external and internal capsule joining to build the stem of the fork. Edema of the medial lentiform margin forms the medial arm, which splits into two along the medullary laminae to envelop the globus pallidus (3). The lentiform fork sign is nonspecific for uremic encephalopathy. Differential diagnosis of pathologic conditions manifesting with this sign includes severe metabolic acidosis, ketoacidosis, dialysis disequilibrium syndrome, and intoxication (ie, methanol, ethylene glycol); this can also be drug induced (ie, metformin) (4).Disclosures of conflicts of interest: D.A.L. No relevant relationships. J.L. No relevant relationships.

Haemodiafiltration as a treatment option in refractory life‐threatening diabetic ketoacidosis

Abstract Background: Fulminant diabetic ketoacidosis (DKA) with a pH of &lt;6.9 can be refractory to DKA management protocols and there is no consensus/evidence to suggest intravenous bicarbonate use. Here we attempt to describe a case of fulminant DKA without renal failure where haemofiltration was done for severe metabolic acidosis with excellent results.Case history: A 23‐year‐old female presented to the emergency department via ambulance after out‐of‐hospital arrest and returned to spontaneous circulation after resuscitation. She was found to be in severe DKA with pH of 6.752, HCO3 of 1.3mmol/L, lactate 3.1mmol/L and creatinine 133μmol/L; and despite maximal DKA treatment with maximum insulin infusion titration, at 15 units per hour and 5 litres of IV fluid, remained in severe metabolic acidosis with pH 6.772. After discussion with critical care and endocrine colleagues regarding options of using intravenous bicarbonate therapy versus haemofiltration, she was put on haemofiltration which resolved the metabolic acidosis completely within 12 hours.Discussion: Our patient with severe refractory DKA responded to haemofiltration with resolution of severe metabolic acidosis; we feel that haemofiltration in these situations may be considered as an option to correct persistent metabolic acidosis in refractory fulminant DKA. Copyright © 2022 John Wiley &amp; Sons.

76 A Report on 83 Patients with Suspected Methanol Poisoning from Philippine Coconut Wine (Lambanog) Seen at East Avenue Medical Center: A Case Series

Lambanog or Philippine Coconut wine is locally made distilled alcohol made from coconut sap and is well known for its strong alcohol content (40-45%). Severe methanol intoxication from Lambanog wine is rare but frequently lethal. Poor prognosis criteria include coma and seizure and severe metabolic acidosis. We present epidemiological and clinical data from a recent toxicologic mass casual incident involving suspected methanol poisoning. The management of methanol poisoning includes standard supportive care, correction of metabolic acidosis, administration of folinic acid, provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and enhance methanol and formate elimination.

Metabolic acidosis post kidney transplantation.

Metabolic acidosis, a common complication in patients with chronic kidney disease (CKD), results in a multitude of deleterious effects. Though the restoration of kidney function following transplantation is generally accompanied by a correction of metabolic acidosis, a subset of transplant recipients remains afflicted by this ailment and its subsequent morbidities. The vulnerability of kidney allografts to metabolic acidosis can be attributed to reasons similar to pathogenesis of acidosis in non-transplant CKD, and to transplant specific causes, including donor related, recipient related, immune mediated factors, and immunosuppressive medications. Correction of metabolic acidosis in kidney transplantation either with alkali therapy or through dietary manipulations may have potential benefits and the results of such clinical trials are eagerly awaited. This review summarizes the published evidence on the pathogenesis and clinical consequences of chronic metabolic acidosis in kidney transplant recipients.

Effect of Correction of Metabolic Acidosis on Serum Interleukin 10 Levels in Chronic Hemodialysis Patients

Effect of Correction of Metabolic Acidosis on Serum Interleukin 10 Levels in Chronic Hemodialysis Patients

Methanol Toxicity: An Emergency Department and Toxicologist Dilemma – Methanol Case Series, Investigation of Medical Professionals’ Knowledge, and Review of The Literature

Methanol is a clear, colorless, highly toxic alcohol widely used as paint, varnish removers, automotiveradiators, and washer fluid. Methanol intoxication incidence can be due to accidental, occupational,suicidal exposure or following an adulterated liquor’s ingestion. Methanol is not toxic itself but will bemetabolized to the exceedingly poisonous formaldehyde and formic acid. Methanol ingestion ends inwide anion-gap metabolic acidosis and devastating neurological complications, including drowsinessto coma and devastating intracranial hemorrhages. Severe toxicities can occur with an intake of 0.25ml/kg of 100% methanol. The blood level of methanol above 25 mg/dl is considered highly toxic.Methanol reaches its peak plasma levels within an hour. Treatment guidelines include antidotal therapy,hemodialysis, and metabolic acidosis correction. Due to methanol’s poisoning severity and graveoutcome of the affected cases, we had to present 4 case series for methanol intoxication, each with itsclinical manifestations and laboratory findings, to enlighten the medical practitioners about possiblecauses, presentations, and treatment modalities of such severe toxicity.Four methanol poisoning case series with different presentations were discussed in the current work.A questionnaire about methanol poisoning awareness was distributed through the ER physicians’ andnurses’ mail to investigate their ability to diagnose and treat methanol poisoning cases.More training of ER medical staff on toxicological presentations is highly recommended. Clinical andanalytical toxicologists should have a more prominent role in the management of such cases. Morelight and international publicity should be shed upon the methanol toxicity outbreaks encounteredglobally, with frequently updating the diagnostic and therapeutic guidelines following an evidencebasedapproach are highly recommended.

Базові основи та принципи керованої інфузійної терапії у хворих із невідкладною хірургічною патологією органів черевної порожнини

За останні п’ятнадцять років кількість ургентних лапаратомій становила 36–58 % з летальністю 30–80 %. Однією з головних причин такої високої смертності є гіповолемія, що формує гемодинамічні порушення, тканинну гіпоксію і розвиток поліорганної недостатності. Основним методом її лікування є поповнен­ня дефіциту об’єму циркулюючої крові. Препаратами вибору вважаються кристалоїди. Прогнозування ефектів кристалоїдних розчинів легко провести за допомогою фізико-хімічної моделі кислотно-лужної рівноваги Стюарта. Згідно теорії, характеристиками збалансованого кристалоїдного розчину є: SIDinf = 24 мEqL–1; відповідність вмісту електролітів до їх концентрації в плазмі; наявність у складі органічних іонів, що запобігають підвищенню концентрації Cl– в інфузійному розчині і є донаторами резервної лужності. Виходячи з цього ми виділяємо серед кристалоїдних розчинів незбалансовані (0,9% розчин NaCl); частково збалансовані (розчини Рінгера лактат і Хартмана); повністю збалансовані розчини (плазмаліт, плазмаліт А, стерофундін, стерофундін ISO). Використання незбалансованих розчинів небезпечно у зв’язку з розвитком гіперхлоремічного ацидозу. Використання частково збалансованих кристалоїдних розчинів може формувати або посилювати лактатацидоз в умовах тканинної гіпоксії і/або дисфункції печінки. Інфузія збалансованих розчинів дозволяє швидко коригувати метаболічний ацидоз.

Triumvirate to treat mucormycosis: Interplay of pH, metal ions and antifungal drugs

Mucormycosis is a rare fungal infection mainly affecting immunocompromised patients. Recently, an alarming rise in cases of mucormycosis was observed in patients undergoing COVID-19 treatment. Commonly, this fungal infection is caused by Rhizopus spp., Mucor spp., and Lichtheimia spp., although the genera of other Mucorales such as Saksenaea, Rhizomucor, Cunninghamella, and Apophysomyces may also be involved. A number of factors such as high concentration of zinc, iron and hypoxia induced acidosis promote the growth of fungi, thereby increasing the risk of mucormycosis multiple folds. Iron chelators (deferasirox and deferiprone) and zinc chelators (clioquinol, phenanthroline and N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethane-1,2-diamine) have been reported to inhibit the growth of fungi in a number of in vitro and animal studies. Correction of metabolic acidosis by administration of bicarbonate or glycine reduces the susceptibility of patients to the invasion by fungal species. However, these factors have largely been ignored while deciding the treatment strategy for mucormycosis and first line treatment for the management of mucormycosis continues to be the expensive lipid based formulation of amphotericin B. Treatment with isavuconazole which is proposed as the second choice is reported to be more cost effective. Therefore, it is proposed that a combination of antifungal agent (isavuconazole) with zinc and iron chelators (deferasirox and clioquinol respectively) along with alkalizer (glycine buffer) could be an effective and multi-target approach for the treatment of mucormycosis while being cost effective also.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency presenting as ketosis with hyperglycemia: A case report

We describe a case of previously normal 22-month-old male who presented with vomiting, loose motions, lethargy, and seizures for 1 day. He had high anion gap metabolic acidosis, hyperglycemia, and ketosis managed elsewhere as diabetic ketoacidosis. Early management included hemodynamic stabilization, mechanical ventilation, correction of metabolic acidosis, seizure control, and later peritoneal dialysis. He was finally diagnosed with succinyl CoA 3 ketoacid transferase deficiency, a disorder of ketone metabolism usually presents with metabolic acidosis, ketosis, and hypoglycemia. Most cases present during the neonatal period (50%) and remain up to 20 months of age. The pathognomic finding is a nonspecific elevation on ketones in urine gas chromatography–mass spectrometry. Genomic sequencing is confirmatory.

Clinical relevance of abstruse transport phenomena in haemodialysis.

ABSTRACTHaemodialysis (HD) utilizes the bidirectional properties of semipermeable membranes to remove uraemic toxins from blood while simultaneously replenishing electrolytes and buffers to correct metabolic acidosis. However, the nonspecific size-dependent transport across membranes also means that certain useful plasma constituents may be removed from the patient (together with uraemic toxins), or toxic compounds, e.g. endotoxin fragments, may accompany electrolytes and buffers of the dialysis fluids into blood and elicit severe biological reactions. We describe the mechanisms and implications of these undesirable transport processes that are inherent to all HD therapies and propose approaches to mitigate the effects of such transport. We focus particularly on two undesirable events that are considered to adversely affect HD therapy and possibly impact patient outcomes. Firstly, we describe how loss of albumin (and other essential substances) can occur while striving to eliminate larger uraemic toxins during HD and why hypoalbuminemia is a clinical condition to contend with. Secondly, we describe the origins and mode of transport of biologically active substances (from dialysis fluids with bacterial contamination) into the blood compartment and biological reactions they elicit. Endotoxin fragments activate various proinflammatory pathways to increase the underlying inflammation associated with chronic kidney disease. Both phenomena involve the physical as well as chemical properties of membranes that must be selected judiciously to balance the benefits with potential risks patients may encounter, in both the short and long term.

Hemofiltration in the Management of Severe Pediatric Burns: Experience in a UK Burns Centre and Systematic Review.

Pediatric burns are life-threatening injuries due to the acute injury and secondary complications. In acute-phase burns, hypovolemia and vasoconstriction cause renal impairment. Sepsis and multiorgan failure compound the problem resulting in morbidity and mortality. This paper outlines 5 years' experience using hemofiltration in major pediatric burns, and a review of the current literature. Retrospective patient data collection was undertaken identifying relevant pediatric burns undergoing Continuous Veno-Venous Hemofiltration. Data were analyzed to identify demographics, indication, duration of therapy, and outcomes. A systematic review was also performed using PRISMA principles. PubMed, Science Direct, and OVID databases were explored and relevant papers were included. From January 2015 to December 2019, hemofiltration was utilized in five cases. Age range 3 to 15 years (mean: 12), four males/one female, and mean weight 56 kg (12-125 kg). TBSA 21% to 61% (mean: 37.6%), mechanism of injury was scald-60%, flame-40%. Overall survival was 100%. Three patients were filtered for a brief period during the first 24 hours to correct metabolic acidosis and control temperature. Two patients required prolonged therapy. All patients recovered without further long-term renal support. A total of 3814 papers were identified for systematic review. Three were considered relevant for inclusion. This paper reflects the benefits of hemofiltration in the management of severe pediatric burns. Renal replacement therapy is useful in managing metabolic acidosis, temperature control, and renal failure. The current literature supports judicious use on a patient-by-patient basis. Given the lack of evidence in the literature, further studies are required to establish guidelines for the use of hemofiltration in pediatric burns.

Safety and effectiveness of rheosorbilact detoxification therapy in stage 1–3 CKD

The problem of detoxification therapy, in particular for kidney disease, is an important component of modern treatment. Renal dysfunction significantly complicates detoxification measures for at least two reasons. The first is to reduce the clearance of toxic substances, increase their content and redistribution in body tissues while reducing the glomerular filtration rate. The second reason is a change in the pharmacodynamics of detoxification drugs due to decreased renal function. Rheosorbilact is a hyperosmolar crystalloid electrolyte solution for infusion, which has detoxifying, rheological and alkalizing action with stimulation of intestinal motility. The drug is used to correct metabolic acidosis without causing sharp fluctuations in pH, due to the sodium lactate content, the effect of which manifested itself in 20–30 minutes after administration. Another important component of the drug is sorbitol, which in the form of an isotonic solution has a disaggregating effect, improving microcirculation and tissue perfusion. Sodium chloride in the drug replenishes the deficiency of sodium and chlorine ions, performing a rehydrating effect and increasing the volume of circulating blood, increasing diuresis, and calcium chloride replenishes the deficiency of calcium ions, reducing the permeability of the vascular wall and thus preventing the development of inflammatory reactions. The article presents a detailed analysis of the use of rheosorbilact with an emphasis on kidney disease and their function. Rheosorbilact can be used effectively and safely at a dose of 200 ml at a body weight of less than 60 kg and up to 400ml at a body weight of more than 60 kg twice a day at an estimated glomerular filtration rate of more than 45 ml/min/m2 and no decompensated heart failure and stage III hypertension.

Nutritional Approaches for the Management of Metabolic Acidosis in Chronic Kidney Disease.

Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis.

Metabolic Acidosis and Cardiovascular Disease in CKD

Rationale & ObjectiveMetabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear.Study DesignRetrospective cohort study.Setting & ParticipantsThe Optum De-identified Electronic Health Records Dataset, 2007–2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m2. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart.PredictorSerum bicarbonate as a continuous variable.OutcomePrimary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome.Analytical ApproachCox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+.ResultsA total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9–4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961–0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97–0.98), 0.98 (95% CI, 0.97–0.99), 0.96 (95% CI, 0.96–0.97), and 0.94 (95% CI, 0.93–0.94), respectively, for every 1-mEq/L increase in serum bicarbonate.LimitationsPossible residual confounding.ConclusionsMetabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.

Recent evidence on the effect of treatment of metabolic acid on the progression of kidney disease.

Preclinical and epidemiological studies have shown an association between acidosis and progression of chronic kidney disease (CKD) and kidney fibrosis. This review discusses the recent trials evaluating the effect of treatment of metabolic acidosis on kidney outcomes. The emerging evidence suggests that bicarbonate treatment may slow the progression of CKD and reduce the risk of kidney failure. However, high-certainty evidence on the efficacy and safety of alkali therapy is still lacking. Ongoing studies are evaluating the effect of veverimer, a novel nonabsorbable polymer, on clinical kidney outcomes. Recent studies indicate a potential benefit from reduction in acid load in patients with CKD. Whilst it is reasonable that clinicians institute acid-lowering interventions in CKD patients with acidosis, adequately powered trials are required to evaluate the benefit of correction of metabolic acidosis to delay kidney disease progression.

Euglycemic diabetic ketoacidosis: A missed diagnosis.

Euglycemic diabetic ketoacidosis (DKA) is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose (less than 11 mmol/L). The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units; it may delay diagnosis and treatment causing worse outcomes. Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus. With the addition of sodium/ glucose cotransporter-2 inhibitors in diabetes mellitus management, euglycemic DKA incidence has increased. The other causes of euglycemic DKA include pregnancy, fasting, bariatric surgery, gastroparesis, insulin pump failure, cocaine intoxication, chronic liver disease and glycogen storage disease. The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit, milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio. Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones. The diagnostic workup includes arterial blood gas for metabolic acidosis, serum ketones and exclusion of other causes of high anion gap metabolic acidosis. Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration, electrolytes deficit and insulin replacement. The dextrose-containing fluids should accompany intravenous insulin to correct metabolic acidosis, ketonemia and to avoid hypoglycemia.

High serum bicarbonate and adverse outcomes in hemodialysis patients

Metabolic acidosis is a usual complication of progressive chronic kidney disease and is associated with morbidity and mortality. The correction of metabolic acidosis is a main goal of dialysis. In prevalent hemodialysis patients, acid-base homeostasis depends on many factors, mainly net acid production, amount of alkali given by the dialysate bath and duration of the interdialytic period. At present, the main concern in prevalent hemodialysis patients is not over patients with metabolic acidosis, but rather about the growing numbers of patients with metabolic alkalosis. Several large cohort studies have shown significant associations between high predialysis bicarbonate, as well as blood pH, and morbidity and mortality risk. Based on recent guidelines, we should keep predialysis serum bicarbonate concentrations at 24-26 mEq/L, although this is opinion-based and there is no consensus on the issue. Furthermore, there should be specific focus on the patient´s nutritional status and reversible comorbidities.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study

BackgroundMetabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood.MethodThis was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < –4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model.ResultsWe screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality.ConclusionsEarly metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.