Treatment Of Metabolic Acidosis Research Articles

Effects of dietary interventions for metabolic acidosis in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD. Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data. Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies. Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required.

Rhododendron poisoning in alpacas (Vicugna pacos) in Northern Germany

Poisoning is often suspected to be the origin of disease in South American camelids (SACs) by owners, but only in a few cases this assumption can be confirmed. In small ruminants, rhododendron poisoning is a common emergency for livestock veterinarians. However, this condition has rarely been reported in SACs so far. This paper provides information regarding clinical findings, hematology, clinical chemistry, and treatment of four alpacas after presumed intake of rhododendron leaves including pathological findings of one of the animals. Rhododendron leaves contain grayanatoxins that lead to hyperpolarization of excitable cells. Clinical signs that were observed in the presented alpacas comprised: salivation, dehydration, decreased motility of compartment 1, uncoordinated regurgitation, and cardiac arrhythmia. Clinical chemistry revealed that rhododendron poisoning was associated with metabolic acidosis and azotaemia, hyponatremia and hyperkalemia. Most striking macroscopic and histopathological findings included gastric ulceration, and renal infarcts along with inflammatory changes. Leaves of Rhododendron spp. were identified in the forestomach content of this animal. Affected animals were treated symptomatically as there is no specific antidote in rhododendron poisoning. This included parenteral rehydration, treatment of metabolic acidosis (infusion of sodium bicarbonate solution), and oral administration of activated charcoal to bind potential toxins. In addition, antibiotic treatment might be necessary to prevent aspiration pneumonia in case of uncoordinated regurgitation. Of the four animals, the worst affected alpaca was euthanized, one had minimal signs and two responded to supportive care and recovered. In conclusion, rhododendron poisoning might be fatal for alpacas in individual cases and therefore rhododendron bushes should not be placed in the habitat of SACs.

Metabolic acidosis is undertreated and underdiagnosed: a retrospective cohort study.

Guidelines recommend treatment of metabolic acidosis (MA) in patients with chronic kidney disease (CKD), but the diagnosis and treatment rates in real-world settings are unknown. We investigated the frequency of MA treatment and diagnosis in patients with CKD. In this retrospective cohort study, we examined administrative health data from two US databases [Optum's de-identified Integrated Claims+Clinical Electronic Health Record Database (US EMR cohort; 1 January 2007 to 30 June 2019) and Symphony Health Solutions IDV® (US claims cohort; 1 May 2016 to 30 April 2019)] and population-level databases from Manitoba, Canada (1 April 2006 to 31 March 2018). Patients who met laboratory criteria indicative of CKD and chronic MA were included: two consecutive estimated glomerular filtration results <60mL/min/1.73m2 and two serum bicarbonate results 12 to <22mEq/L over 28-365 days. Outcomes included treatment of MA (defined as a prescription for oral sodium bicarbonate) and a diagnosis of MA (defined using administrative records). Outcomes were assessed over a 3-year period (1 year pre-index, 2 years post-index). A total of 96184 patients were included: US EMR, 6179; Manitoba, 3223; US Claims, 86782. Sodium bicarbonate treatment was prescribed for 17.6%, 8.7% and 15.3% of patients, and a diagnosis was found for 44.7%, 20.9% and 20.9% of patients, for the US EMR, Manitoba and US Claims cohorts, respectively. This analysis of 96184 patients with laboratory-confirmed MA from three independent cohorts of patients with CKD and MA highlights an important diagnosis and treatment gap for this disease-modifying complication.

Management of Metabolic Acidosis in Chronic Kidney Disease: Past, Present, and Future Direction.

Chronic kidney disease(CKD) is a major global epidemic associated with increased morbidity and mortality. Despite the effectiveness of kidney protection strategies of hypertension, diabetes, and lipid control and use of newer hypoglycemic agents and anti-angiotensin II drugs, the nephropathy in CKD continues unabated toward irreversible kidney failure. Thus, interventions targeting modifiable risk factors in CKD such as metabolic acidosis (MA) are needed. Acid reduction with sodium-based alkali has been shown to be an effective kidney-protection strategy for patients with CKD and reduced glomerular filtration rate (GFR). Small-scale studies reveal diets emphasizing ingestion of plant-sourced over animal-sourced protein reduce dietary acid, improve MA, and slow further nephropathy progression in patients with CKD and reduced GFR. Additionally, veverimer, an investigational, nonabsorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as a novel treatment for MA. As further studies define how to best use these interventions for kidney protection, clinicians must become aware of their potential utility in the management of patients with CKD. The aim of the present review is to explore the various intervention strategies that increase or normalize serum [HCO3-] in patients with CKD-associated MA or low normal serum [HCO3-] that may further slow progression of CKD.

Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD.

Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth. To describe longitudinal associations between MA and linear growth, we used serum bicarbonate levels, height measurements, and standard deviation (z scores) of children enrolled in the prospective cohort study Chronic Kidney Disease in Children. Analyses were adjusted for covariates recognized as correlating with poor growth, including demographic characteristics, glomerular filtration rate (GFR), proteinuria, calcium, phosphate, parathyroid hormone, and CKD duration. CKD diagnoses were analyzed by disease categories, nonglomerular or glomerular. The study population included 1082 children with CKD: 808 with nonglomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels ≤22 mEq/L were associated with worse height z scores in all children. Longitudinally, serum bicarbonate levels ≤18 and 19-22 mEq/L were associated with worse height z scores in children with nonglomerular CKD causes, with adjusted mean values of -0.39 (95% CI, -0.58 to -0.2) and -0.17 (95% CI, -0.28 to -0.05), respectively. Children with nonglomerular disease and more severe GFR impairment had a higher risk for worse height z score. A significant association was not found in children with glomerular diseases. We also investigated the potential effect of treatment of MA on height in children with a history of alkali therapy use, finding that only persistent users had a significant positive association between their height z score and higher serum bicarbonate levels. We observed a longitudinal association between MA and lower height z score. Additionally, persistent alkali therapy use was associated with better height z scores. Future clinical trials of alkali therapy need to evaluate this relationship prospectively.

Етіологія, патогенез та інтенсивна терапія метаболічного ацидозу

У статті надані дані щодо етіології, патогенезу, клінічних проявів, принципів діагностики та лікування метаболічних ацидозів: діабетичного і недіабетичного кетоацидозу, лактатацидозу в дорослих і дітей. Викладено сучасні напрямки інфузійної терапії кетоацидозу і лактатацидозу із застосуванням новітніх вітчизняних інфузійних засобів. У своїй статті автори зіставили алгоритми лікування кетоацидозу і лактатацидозу з рекомендаціями Британського товариства клінічної діабетології і Американської асоціації нефрологів, роблячи поправку на можливості вітчизняних лабораторних досліджень. Характерною особливістю деяких форм кислотно-основного дисбалансу, що часто зустрічаються, є тісне переплетення ушкоджуючих або пристосувальних елементів, чіткої межі між якими не існує. Багатофакторність і патогенетична неоднозначність порушень кислотно-основного гомео­стазу зумовлюють значні розбіжності в оцінці прогностичної значимості і стратегії лікування його складних форм. У клінічній практиці це часто призводить до невиправданої схематизації, «знеособлення» терапії, або, що ще гірше, до прагнення враховувати параметри кислотно-основного стану тільки при зміщенні рН в області загрожуючих життю значень.

Effect of Oral Sodium Bicarbonate Treatment on 24-Hour Ambulatory Blood Pressure Measurements in Patients With Chronic Kidney Disease and Metabolic Acidosis.

Background: Sodium bicarbonate supplementation is a mainstay in the treatment of metabolic acidosis in patients with chronic kidney disease (CKD). Recent studies showed reduction of progression of CKD and reduced all-cause mortality. However, additional sodium loading could worsen arterial hypertension, a well-known contributor to progression of CKD. This patient-relevant and economically negative side effect is under-studied in prospective studies up until now.Objective: The aim of this study was to analyze the effect of sodium bicarbonate treatment on arterial blood pressure at baseline and after 8 weeks.Methods: The SoBic study is an ongoing randomized controlled trial, in which patients with CKD receive either a high dose of oral sodium bicarbonate or a rescue treatment, if necessary. We used standardized office blood pressure and 24-hour ambulatory blood pressure monitoring (24h-ABPM). Regression models were adjusted for estimated glomerular filtration rate and change of antihypertensives.Results: 47 subjects were enrolled and the mean age was 57 (±14.6) years and 18 (38%) were female. In 43 randomized subjects with sufficiently performed 24h-ABPM neither systolic 24h-ABPM (2.522; 95%CI: −2.364, 7.408; mmHg) nor diastolic 24h-ABPM (0.868; 95%CI: −2.411, 4.147; mmHg) was affected by study group allocation. When looking at the effect of individual sodium bicarbonate dose on 24h-ABPM, the fully adjusted model suggested an increase of 0.047 (95%CI: −0.026, 0.119) mmHg by each mg/kg per day increase of sodium bicarbonate dose.Conclusion: Sodium bicarbonate supplementation over 8 weeks did not significantly increase blood pressure measured by 24h-ABPM in CKD patients.Trial Registration: EUDRACT Number: 2012-001824-36; 12/07/2012 (https://www.clinicaltrialsregister.eu).

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease.

Current management of metabolic acidosis in patients with chronic kidney disease (CKD) relies on dietary intervention to reduce daily endogenous acid production or neutralization of retained acid with oral alkali (sodium bicarbonate, sodium citrate). Veverimer is being developed as a novel oral treatment for metabolic acidosis through removal of intestinal acid, resulting in an increase in serum bicarbonate. Veverimer is a free-amine polymer that combines high capacity and selectivity to bind and remove hydrochloric acid (HCl) from the gastrointestinal (GI) tract. In vitro studies demonstrated that veverimer had a binding capacity of 10.7 ± 0.4 mmol HCl per gram of polymer with significant binding capacity (>5 mmol/g) across the range of pH values found in the human GI tract (1.5-7). Upon protonation, veverimer bound chloride with high specificity but showed little or no binding of phosphate, citrate, or taurocholate (<1.5 mmol/g), which are all anions commonly found in the human GI tract. Administration of veverimer to rats with adenine-induced CKD and metabolic acidosis resulted in a significant increase in fecal chloride excretion and a dose-dependent increase in serum bicarbonate to within the normal range compared with untreated controls. Absorption, distribution, metabolism, and excretion studies in rats and dogs dosed with 14C-labeled veverimer showed that the polymer was not absorbed from the GI tract and was quantitatively eliminated in the feces. Acid removal by veverimer, an orally administered, nonabsorbed polymer, may provide a potential new treatment for metabolic acidosis in patients with CKD. SIGNIFICANCE STATEMENT: Metabolic acidosis is a complication of chronic kidney disease (CKD) as well as a cause of CKD progression. Veverimer is a high-capacity, selective, nonabsorbed, hydrochloric acid-binding polymer being developed as a treatment for metabolic acidosis. Veverimer binds and removes hydrochloric acid from the gastrointestinal tract, resulting in increased serum bicarbonate and the correction of metabolic acidosis. Veverimer is not an ion-exchange resin and does not deliver sodium or other counterions, and so it may be appropriate for patients with CKD with and without sodium-sensitive comorbidities.

Impact of sodium bicarbonate therapy on hemodynamic parameters in infants: a meta-analysis

Objective Sodium bicarbonate is a frequently used electrolyte for the acute treatment of metabolic acidosis in critically ill patients. We performed a systematic review and meta-analysis to determine the effect of sodium bicarbonate on hemodynamics, gas exchange and oximetry in critically children. Methods A systematic review of published manuscripts was conducted to identify studies of children who received sodium bicarbonate as part of the treatment for metabolic acidosis. A meta-analysis was then conducted to determine the impact of sodium bicarbonate on hemodynamics, gas exchange and oximetry. The following parameters were captured: base deficit, heart rate, mean arterial pressure, blood concentration of carbon dioxide, blood concentration of hydrogen ion, and pulse oximetry. Results A total of six studies with 341 patients were included in the analyses. All included studies were completed in critically ill infants with a mean age of 1.1 months. The mean dose of sodium bicarbonate was 1.7 meq/kg with a mean time of 67 min prior to repeat hemodynamics being collected after sodium bicarbonate administration. Base deficit significantly improved with a decrease of 2.80 (p = .001) and the partial pressure of carbon dioxide significantly decreased by a mean of −1.65 mmHg (p = .010). There was no change in heart rate, blood pressure, pH, partial pressure of oxygen, or saturation by pulse oximetry. Conclusion Sodium bicarbonate has a statistically significant but not clinically significant impact on partial pressure of carbon dioxide and base deficit 60 min after sodium bicarbonate administration in critically ill infants. There is no difference noted in pH, partial pressure of oxygen, or saturation by pulse oximetry.

P0001EFFECTS OF VEVERIMER ON SERUM BICARBONATE AND PHYSICAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND METABOLIC ACIDOSIS ARE INDEPENDENT OF ALBUMINURIA: SUBGROUP ANALYSES FROM A RANDOMIZED TRIAL

Abstract Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polymer that binds gastrointestinal hydrochloric acid and results in an increase in serum bicarbonate, is being developed as a treatment for metabolic acidosis in patients with chronic kidney disease (CKD). Metabolic acidosis is a complication of CKD that has deleterious effects on kidney function, bone (demineralization), and muscle (protein catabolism).1 Albuminuria and metabolic acidosis are independently associated with CKD progression and treatment of each may reduce the risk of kidney failure.2,3 We sought to assess (post-hoc) if albuminuria impacts the ability of veverimer to increase serum bicarbonate level and improve physical functioning. Method TRCA-301E is a multicenter, Phase 3, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR 20 - 40 ml/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12 - 20 mEq/L) who were treated for up to 1 year with veverimer (previously TRC101) or placebo, with dose titration targeted to achieve a normal serum bicarbonate. 4 The randomization was performed in a ratio of 4:3 (veverimer:placebo). Results We previously reported4 that, compared with placebo, veverimer significantly increased serum bicarbonate and significantly improved physical function as reported on the Kidney Disease and Quality of Life-Physical Function Domain (KDQOL-PFD) (e.g., walking several blocks, climbing stairs) and as measured objectively using the 5-times repeated chair stand test with a safety profile that was similar to placebo. Baseline characteristics of the subgroups of patients by baseline urine albumin to creatinine ratio (UACR) ≤ 300 vs. &amp;gt;300 mg/g are shown in the Table. Neither albuminuria (log UACR) as a continuous covariate nor the presence of UACR &amp;gt; 300 mg/g had an effect on the efficacy of veverimer treatment in correction of acidosis or improvement of physical function (interaction p-values &amp;gt;0.4). In patients with UACR &amp;gt; 300 mg/g, at Week 52, serum bicarbonate increased by 4.1 (0.5) mEq/L on veverimer (p = 0.047 vs. placebo) and a significantly higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (59% vs. 30%, p = 0.014). Patient-reported limitations of physical function (KDQOL-PFD) improved in the veverimer vs. placebo group (+10.4 vs. +1.2 seconds, respectively, p = 0.034). Objective physical performance on the chair stand test at Week 52 also improved in the veverimer group vs. placebo (p &amp;lt; 0.001). In patients with UACR ≤ 300 mg/g, at Week 52, serum bicarbonate increased by 5.2 (0.5) mEq/L on veverimer (p = 0.003 vs. placebo) and a numerically higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (65% vs. 45%, p = 0.063). KDQOL-PFD improved in the veverimer vs. placebo group (+12.5 vs. -2.8 seconds, respectively, p = 0.001). The chair stand test at Week 52 also improved in the veverimer group vs. placebo (p = 0.002). Conclusion The drug candidate veverimer effectively treated metabolic acidosis and improved the ability to repeatedly stand from a seated position and physical function related to daily activities independent of albuminuria, and therefore independent of the kidney injury reflected by albuminuria.

P0009EVALUATION OF THE POTENTIAL FOR DRUG INTERACTIONS WITH VEVERIMER

Abstract Background and Aims Veverimer is an investigational drug being developed as an orally administered hydrochloric acid binder for the treatment of metabolic acidosis associated with chronic kidney disease (CKD). In clinical studies, treatment with veverimer safely and effectively increased serum bicarbonate and improved objective and subjective measures of physical functioning1-3. Veverimer, a free-amine polymer, is not systemically absorbed; therefore, its potential for drug-drug interactions (DDIs) is limited to those that occur in the gastrointestinal (GI) tract (i.e., direct binding or indirect effects resulting from transient increases in gastric pH). We assessed the potential for DDIs with veverimer both in vitro and in vivo in healthy subjects. Methods In vitro binding to veverimer was evaluated with 16 drugs of varying molecular weight and charge. In a separate study, the effect of veverimer on gastric pH was measured continuously in vivo in healthy subjects using a microelectrode pH probe placed in the gastric compartment. Human DDI studies were conducted with 4 orally administered drugs, including those that demonstrated the most in vitro binding to veverimer and those with pH-dependent solubility (furosemide, aspirin, warfarin, dabigatran). Results Veverimer did not bind to any of the positively charged, neutral or zwitterionic drugs tested in vitro. It bound to 3 small (MW &amp;lt;332 Da), negatively charged drugs (aspirin, ethacrynic acid, furosemide); these interactions were reduced or eliminated in the presence of physiologically relevant concentrations of chloride. Neither furosemide nor aspirin showed clinically meaningful changes in pharmacokinetic parameters when coadministered with veverimer in human DDI studies (Figure 1). Veverimer increased gastric pH by ∼3.0 and 1.5 pH units in fasted and fed subjects, respectively. The increase in gastric pH was short-lived, with a peak within 1 hour after dosing and a return to baseline after ∼1.5 hours and ∼3 hours under fasting and fed conditions, respectively. The effect of veverimer on gastric pH was similar in the presence and absence of omeprazole. No clinically meaningful changes in systemic exposure, as indicated by Cmax and AUC, were observed when 3 drugs with pH-dependent solubility were coadministered with veverimer in human DDI studies (Figure 1). Conclusions In human DDI studies, we observed: a) no effect of veverimer on the bioavailability of drugs with physicochemical characteristics most susceptible to direct binding to the polymer; b) small, short-lived effects of veverimer on gastric pH; and c) no effect of veverimer on the bioavailability of drugs with pH-sensitive solubility. Therefore, it is concluded that there is a negligible risk of veverimer involvement in clinically significant DDIs.

The Evaluation and Treatment of Metabolic Acidosis

Metabolic acidosis has a wide array of etiologies making the initial evaluation imperative in order to identify the proper treatment pathway. The clinical sequela of metabolic acidosis can often be vague and nonspecific. This underscores the importance of being able to comfortably recognize and evaluate acid-base disturbances. The diagnostic modalities used to evaluate metabolic acidosis have existed for quite some time, though the validity and usefulness of particular metrics have shown superior to others. Similarly, as our understanding of disease processes progresses, the conditions that warrant and respond to the use of base therapy are rare. Metabolic acidosis has potentially grave consequences to patient outcomes. As a result, timely diagnosis and recognition of treatment options is vital.

58 Mechanism of Action and Onset of Effect of Veverimer, A Novel Acid Binder for the Treatment of Metabolic Acidosis Associated with Chronic Kidney Disease (CKD)

58 Mechanism of Action and Onset of Effect of Veverimer, A Novel Acid Binder for the Treatment of Metabolic Acidosis Associated with Chronic Kidney Disease (CKD)

Bicarbonate use and mortality outcome among critically ill patients with metabolic acidosis: A meta analysis

BackgroundThe use of sodium bicarbonate in the treatment of metabolic acidosis in critically ill subjects has long been a subject of debate. Despite empiric use in the setting of severe acidemia in critically ill patients, there is little data looking into the role of sodium bicarbonate in the treatment of severe metabolic acidosis in the intensive care unit (ICU) setting. MethodsWe conducted a comprehensive search of Pubmed and Cochrane Central Register of Controlled Trials addressing bicarbonate use in the metabolic acidosis in the intensive care unit (ICU) setting. We examined mortality as end point. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated for all outcomes using a random-effect model. ResultsThe final search yielded 202 articles of which all were screened individually. A total of 11 studies were identified but 6 studies were excluded due to irrelevance in mortality outcome and methodology. Analysis was done separately for observational studies and randomized controlled trials. The pooled OR [95% CI] for mortality with bicarbonate use in the observational studies was 1.5 [0.62–3.67] with heterogeneity of 67%, while pooled OR for mortality in the randomized trials was 0.72 [0.49–1.05] (figure 2). In combining all studies, the pooled odds ratio was 0.93 95% [0.69–1.25] but with heterogeneity of 63%. After sensitivity analysis with removing the study done by Kim et al. 2013, heterogeneity was 0% with OR 0.8 [0.59–1.10]. ConclusionThere is no significant difference in mortality in the use of bicarbonate among critically ill patients with high anion gap metabolic acidosis predominantly driven by lactic acidosis.

Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study

BackgroundMetabolic 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.MethodsWe 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.ResultsA 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.ConclusionIn 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.

Drug removal of gastric acid: a novel treatment of metabolic acidosis

Metabolic acidosis is a complication of chronic kidney disease1,2 associated with muscle wasting and reduced muscle strength, bone disease, reduced growth in children, progression of chronic kidney disease, and increased mortality.3 Treatment of metabolic acidosis with base therapy in patients with chronic kidney disease is recommended by most clinical practice guidelines.4 The base is usually given as sodium bicarbonate, sodium citrate, or potassium citrate and by increasing sources of citrate (fruit and vegetables).

Treatment of metabolic acidosis with an intestinal binder

Treatment of metabolic acidosis with an intestinal binder

Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial

Patients with advanced chronic kidney disease lose the capacity to fully excrete endogenous acid, resulting in chronic metabolic acidosis that increases the risk of disease progression and causes muscle catabolism and bone resorption. Veverimer, a non-absorbed, counterion-free, polymeric drug, selectively binds and removes hydrochloric acid from the gastrointestinal lumen, unlike current oral sodium bicarbonate therapy for metabolic acidosis that only neutralises accumulated acid. We assessed the efficacy and safety of veverimer as a treatment for metabolic acidosis in patients with chronic kidney disease. We did a multicentre, parallel, randomised, double-blind, placebo-controlled study at 37 sites (hospitals and specialty clinics) in Bulgaria, Croatia, Georgia, Hungary, Serbia, Slovenia, Ukraine, and the USA. Eligible participants were patients aged 18-85 years with non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate of 20-40 mL/min per 1·73 m2) and metabolic acidosis (serum bicarbonate concentration of 12-20 mmol/L). Patients were randomly assigned (4:3) to veverimer 6 g/day or placebo for 12 weeks while they consumed their typical diet. Both drugs were taken as oral suspensions in water with lunch. Randomisation was done by study site personnel with a computer-generated randomisation code with balanced permuted blocks (block size of seven) and stratified by baseline bicarbonate (≤18 mmol/L vs >18 mmol/L). Patients and investigators were masked to treatment allocation; however, because the appearance of placebo differed from veverimer, a non-masked site staff member who had no other role in the study dispensed, prepared, and supervised dosing of the study drugs. The composite primary efficacy endpoint was the difference (veverimer-placebo) in the proportion of patients achieving at week 12 either an increase of 4 mmol/L or more from baseline in serum bicarbonate concentration or serum bicarbonate in the normal range of 22-29 mmol/L, assessed in the modified intention-to-treat population (all patients with a baseline and at least one post-baseline serum bicarbonate value). Patients fasted for at least 4 h (consuming only water) before measurements of bicarbonate. Safety was assessed in all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, number NCT03317444. Between Sept 26, 2017, and Feb 9, 2018, we randomly assigned 124 participants to veverimer and 93 to placebo. The composite primary endpoint was met by 71 (59%) of 120 patients in the veverimer group versus 20 (22%) of 89 patients in the placebo group (a difference of 37%, 95% CI 23-49; p<0·0001). The most common body system in which adverse events in the veverimer group occurred was gastrointestinal; of these, non-treatment limiting diarrhoea was the most common event (11 [9%] vs three [3%] in the veverimer and placebo groups, respectively). The most common treatment-related adverse events were gastrointestinal (diarrhoea, flatulence, nausea, and constipation) occurring in 16 (13%) patients with veverimer and five (5%) patients with placebo. Two deaths occurred during the study, both in the placebo group (unstable angina and pneumonia). Veverimer effectively and safely corrected metabolic acidosis. Longer-term studies are warranted to assess the effects of veverimer on physical functioning and to assess other deleterious consequences of metabolic acidosis including progression of chronic kidney disease and bone health. Tricida.

Treatment of Metabolic Acidosis in Altering Inflammatory Biomarkers in Renal Transplant Recipients; A Randomized Clinical Trial

Background: Metabolic acidosis following kidney transplantation can lead to several undesirable effects such as disturbing the protein balance resulting in a negative nitrogen equilibrium, increased protein degradation, and essential amino acid oxidation. Objectives: The current study aimed tocompare the effect of normal saline as a common crystalloid in kidney transplant surgery to reduce the risk of hyperkalemia and sodium bicarbonate on the metabolic acidosis rate after renal transplantation. Methods: A total of 40 patients with end-stage renal disease (ESRD) and candidates receiving renal transplant from a living donor referring to the kidney transplantation department of a University affiliated hospital, Tehran, Iran, that meeting the inclusion criteria of this study, were randomly assigned to the intervention group, who were treated with sodium bicarbonate, and the control group, who were treated with normal saline. The primary outcomes measured in this study were acidosis biomarkers including BE, HCO3, PaCO2, and PH and the secondary outcomes included some inflammatory biomarkers and some renal function biomarkers. Results: The mean ± standard deviation of age in the intervention and control groups was 44.4 ± 12.4 and 40.0 ± 13.0, respectively (P = 0.01). A total of 29 of the participants were male (14 in the intervention group and 15 in the control group), and 11 of them (six in the intervention group and five in the control group) were female. The mean ± standard deviation of change in the concentration of PH, BE, HCO3, and PaCO2 in the intervention and control groups was 0.01 ± 0.1 and -0.08 ± 0.1 (P < 0.001); 0.61 ± 4.2 and -3.8 ± 2.6 (P < 0.001); 0.36 ± 2.9 and -2.67 ± 2.1 (P: 0.001); and 0.8 ± 5.4 and 1.4 ± 5.3 (P: 0.799), respectively. Conclusions: The present study revealed that the patients who received sodium bicarbonate had a better status than the normal saline recipients in terms of the maintenance of acid-base homeostasis, inflammatory indexes, and renal function.

Acidosis láctica por metformina: reporte de caso

Lactic acidosis is defined as the presence of pH<7.35, blood lactate>2.0mmol/L and PaCO2<42mmHg. However, the definition of severe lactic acidosis is controversial. The primary cause of severe lactic acidosis is shock. Although rare, metformin-related lactic acidosis is associated with a mortality as high as 50%. The treatment for metabolic acidosis, including lactic acidosis, may be specific or general, using sodium bicarbonate, trihydroxyaminomethane, carbicarb or continuous haemodiafiltration. The successful treatment of lactic acidosis depends on the control of the aetiological source. Intermittent or continuous renal replacement therapy is perfectly justified, shock being the argument for deciding which modality to use. We report a case of a male patient presenting with metformin poisoning as a result of attempted suicide, who developed lactic acidosis and multiple organ failure. The critical success factor was treatment with continuous haemodiafiltration.