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Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real-world Data Results from the AlcalUN Study.
Beaume, J, Figueres, L, Bobot, M, de Laforcade, L, Ayari, H, Dolley-Hitze, T, Gueutin, V, Braconnier, A, Golbin, L, Citarda, S, et al
Clinical pharmacology and therapeutics. 2022;(1):252-262
Abstract
Oral alkalization with sodium bicarbonate (NaHCO3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO3 -containing or no-NaHCO3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO3 is no longer associated with an ECV increase compared to citrate in real-life settings.
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Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial.
Melamed, ML, Horwitz, EJ, Dobre, MA, Abramowitz, MK, Zhang, L, Lo, Y, Mitch, WE, Hostetter, TH
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(2):225-234
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RATIONALE & OBJECTIVE Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING National Institutes of Health grant. TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT01452412.
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Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial.
Parikh, CR, Liu, C, Mor, MK, Palevsky, PM, Kaufman, JS, Thiessen Philbrook, H, Weisbord, SD
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(2):187-194
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RATIONALE & OBJECTIVE The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design. STUDY DESIGN Longitudinal analysis. SETTING & PARTICIPANTS A subset of participants from the PRESERVE trial. EXPOSURES Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography. OUTCOMES MAKE-D and CA-AKI. ANALYTICAL APPROACH We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com. RESULTS We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants). LIMITATIONS Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings. CONCLUSIONS Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.
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Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas Randomized Clinical Trial.
Timal, RJ, Kooiman, J, Sijpkens, YWJ, de Vries, JPM, Verberk-Jonkers, IJAM, Brulez, HFH, van Buren, M, van der Molen, AJ, Cannegieter, SC, Putter, H, et al
JAMA internal medicine. 2020;(4):533-541
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IMPORTANCE Prevention of postcontrast acute kidney injury in patients with stage 3 chronic kidney disease (CKD) by means of prehydration has been standard care for years. However, evidence for the need for prehydration in this group is limited. OBJECTIVE To assess the renal safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in patients with stage 3 CKD. DESIGN, SETTING, AND PARTICIPANTS The Kompas trial was a multicenter, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands in which 523 patients with stage 3 CKD were randomized in a 1:1 ratio to receive no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion before undergoing elective contrast-enhanced computed tomography from April 2013 through September 2016. Final follow-up was completed in September 2017. Data were analyzed from January 2018 to June 2019. INTERVENTIONS In total, 262 patients were allocated to the no prehydration group and 261 were allocated to receive prehydration. Analysis on the primary end point was available in 505 patients (96.6%). MAIN OUTCOMES AND MEASURES The primary end point was the mean relative increase in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin of less than 10% increase in serum creatinine level). Secondary outcomes included the incidence of postcontrast acute kidney injury 2 to 5 days after contrast administration, mean relative increase in creatinine level 7 to 14 days after contrast administration, incidences of acute heart failure and renal failure requiring dialysis, and health care costs. RESULTS Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P < .001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were €119 (US $143.94) per patient in the prehydration group compared with €0 (US $0) in the no prehydration group (P < .001). Other health care costs were similar. CONCLUSIONS AND RELEVANCE Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety. The findings of this study support the option of not giving prehydration as a safe and cost-efficient measure. TRIAL REGISTRATION Netherlands Trial Register Identifier: NTR3764.
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Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study.
Di Iorio, BR, Bellasi, A, Raphael, KL, Santoro, D, Aucella, F, Garofano, L, Ceccarelli, M, Di Lullo, L, Capolongo, G, Di Iorio, M, et al
Journal of nephrology. 2019;(6):989-1001
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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.
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Prospective, randomized, controlled, open-label study to compare efficacy of a mineral-rich solution vs normal saline after complete ethmoidectomy.
de Gabory, L, Escabasse, V, Boudard, P, de Bonnecaze, G, Rumeau, C, Jankowski, R, Debry, C, Morinière, S, Merino, B, Mortuaire, G, et al
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2019;(2):447-457
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PURPOSES The purpose of this study was to compare the efficacy of a mineral-rich solution vs normal saline solution (0.9% NaCl) following endoscopic complete bilateral ethmoidectomy. METHODS This was a prospective, multicenter, randomized, controlled, open-label trial in subjects suffering from steroid-resistant sinonasal polyposis. Adults performed 4 nasal irrigations of mineral or saline solutions daily for 28 days. Evaluations included subject-reported RHINO quality of life (QoL) and NOSE scores, tolerability, and satisfaction, the Lund-Kennedy endoscopic score and assessments of crusting, secretions and mucociliary clearance (rhinoscintigraphy). RESULTS A total of 189 subjects were randomized. Clinically relevant improvements (> 20 points) in RhinoQOL and NOSE scores were measured in both groups without any significant inter-group difference. Among the subjects with impaired RhinoQOL at pre-inclusion, the change in Impact-RhinoQOL score was significantly superior in mineral-rich vs saline solution at day 21 (p = 0.028) and day 28 (p = 0.027). The Lund-Kennedy score continuously improved in both groups earlier with the mineral-rich solution. Crusts were significantly fewer in number and less severe/obstructive in patients receiving mineral-rich vs saline solution at day 7 (p = 0.026) and day 14 (p = 0.016). Furthermore, secretions disappeared significantly more quickly and were less thick/purulent with mineral-rich solution at day 14 (p = 0.002) and day 21 (p = 0.043). Less epistaxis was reported in the mineral vs saline solution (p = 0.008 at day 21). CONCLUSIONS Our findings indicate that the composition of a nasal irrigation solution influences endoscopic scores and QoL after sinus surgery for patients over 60, those with an initially poor QoL and higher symptom score, and smokers.
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Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.
Jaber, S, Paugam, C, Futier, E, Lefrant, JY, Lasocki, S, Lescot, T, Pottecher, J, Demoule, A, Ferrandière, M, Asehnoune, K, et al
Lancet (London, England). 2018;(10141):31-40
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BACKGROUND Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. METHODS We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. FINDINGS Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. INTERPRETATION In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. FUNDING French Ministry of Health and the Société Française d'Anesthésie Réanimation.
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Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.
Weisbord, SD, Gallagher, M, Jneid, H, Garcia, S, Cass, A, Thwin, SS, Conner, TA, Chertow, GM, Bhatt, DL, Shunk, K, et al
The New England journal of medicine. 2018;(7):603-614
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BACKGROUND Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. METHODS Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. RESULTS The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. CONCLUSIONS Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).
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[Not Available].
Jermini-Gianinazzi, I
Praxis. 2018;(13):729-730
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[Vitamin C+sodium bicarbonate versus sodium bicarbonate alone in preventing contrast-induced nephropathy].
Laroussi, L, Triki, M, Ibn Elhaj, Z, Ben Halima, A, Boukhris, M, Ben Amara, W, Keskes, H, Kraiem, S, Lahidheb, D, Marrakchi, S, et al
Annales de cardiologie et d'angeiologie. 2017;(4):190-196
Abstract
INTRODUCTION Contrast-induced nephropathy (CIN) is a common and severe complication in interventional cardiology. OBJECTIVE The aim of our study was to compare the incidence of contrast-induced nephropathy in two accelerated hydration protocols: the first one by the serum bicarbonate and the second combining the serum bicarbonate and oral vitamin C. METHODS This is a multicenter prospective, randomized study conducted between October 2012 and May 2013, including 160 patients. RESULTS The mean age of our study population was 60.8±9.3 years (36-83 years). The two study groups were comparable in terms of cardiovascular risk factors, concomitant medication, and baseline serum creatinine. The CIN incidence was 6.3% in the vitamin C group and 10% in the control group (P=0.38). No significant difference was observed in terms of CIN incidence between the different subgroups analyzed. CONCLUSION According to our study, ascorbic acid administered orally as part of an accelerated hydration protocol does not reduce the incidence of CIN.