Relationship Between Mortality and Use of Sodium Bicarbonate at the Time of Dialysis Initiation: A Prospective Observational Study

Abstract Background Patients with chronic kidney disease often experience metabolic acidosis. Whether oral sodium bicarbonate can reduce mortality in patients with metabolic acidosis has been debated for years. Hence, this study was conducted to evaluate the utility of sodium bicarbonate in patients who will undergo dialysis therapy. In this study, we investigated the effect of oral sodium bicarbonate therapy on mortality in patients with end-stage kidney disease (ESKD) initiated on dialysis therapy. Methods We conducted an observational study of patients when they started dialysis therapy. There were 17 centres participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis. Data were available on patients’ sex, age, use of sodium bicarbonate, drug history, medical history, vital data, and laboratory data. We investigated whether patients on oral sodium bicarbonate for more than three months before dialysis initiation had a better prognosis than those without sodium bicarbonate therapy. The primary outcome was defined as all-cause mortality. Results The study included 1524 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 1030 were men and 492 women, with a mean age of 67.5 ± 13.1 years. Of these, 677 used sodium bicarbonate and 845 did not; 13.6% of the patients in the former group and 21.2% of those in the latter group died by March 2015 (p < 0.001). Even after adjusting for various factors, the use of sodium bicarbonate independently reduced mortality (p < 0.001). Conclusions The use of oral sodium bicarbonate at the time of dialysis initiation significantly reduced all-cause mortality in patients undergoing dialysis therapy.

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Relationship between mortality and use of sodium bicarbonate at the time of dialysis initiation: a prospective observational study

BMC Nephrology ◽

10.1186/s12882-021-02330-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hikaru Morooka ◽

Junichiro Yamamoto ◽

Akihito Tanaka ◽

Daijo Inaguma ◽

Shoichi Maruyama

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Observational Study ◽

Sodium Bicarbonate ◽

Dialysis Initiation ◽

Dialysis Therapy ◽

All Cause Mortality ◽

Bicarbonate Therapy ◽

Oral Sodium

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Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

The Scientific World JOURNAL ◽

10.1155/2014/627673 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 37

Author(s):

María M. Adeva-Andany ◽

Carlos Fernández-Fernández ◽

David Mouriño-Bayolo ◽

Elvira Castro-Quintela ◽

Alberto Domínguez-Montero

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Negative Impact ◽

Qtc Interval ◽

Bicarbonate Therapy ◽

Proximal Tubular ◽

Acute Metabolic Acidosis ◽

Renal Proximal Tubular

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

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Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT

Health Technology Assessment ◽

10.3310/hta24270 ◽

2020 ◽

Vol 24 (27) ◽

pp. 1-90 ◽

Cited By ~ 1

Author(s):

Miles D Witham ◽

Margaret Band ◽

Huey Chong ◽

Peter T Donnan ◽

Geeta Hampson ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Confidence Interval ◽

Sodium Bicarbonate ◽

Serum Bicarbonate ◽

Advanced Chronic Kidney Disease ◽

Bicarbonate Therapy ◽

Oral Sodium

Background Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. Objectives The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. Design A parallel-group, double-blind, placebo-controlled randomised trial. Setting The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. Participants Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of < 22 mmol/l. Interventions Eligible participants were randomised 1 : 1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg three times daily, increasing to 1 g three times daily if the serum bicarbonate concentration was < 22 mmol/l at 3 months. Main outcome measures The primary outcome was the between-group difference in the Short Physical Performance Battery score at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, 6-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and brain natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life-year was the main outcome. Results In total, 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age of participants was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. A total of 220 (73%) participants were assessed at the 12-month visit. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery score at 12 months (–0.4 points, 95% confidence interval –0.9 to 0.1 points; p = 0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 vs. 400). Time to commencement of renal replacement therapy was similar in both groups (hazard ratio 1.22, 95% confidence interval 0.74 to 2.02; p = 0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at 1 year, with additional costs of £564 (95% confidence interval £88 to £1154) and a quality-adjusted life-year difference of –0.05 (95% confidence interval –0.08 to –0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. Limitations The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small and a benefit from larger doses of bicarbonate cannot be excluded. Conclusions Oral sodium bicarbonate did not improve a range of health measures in people aged ≥ 60 years with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual participant meta-analysis would be helpful to determine which subgroups, if any, are more likely to benefit and which treatment regimens are more beneficial. Trial registration Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.

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

Frontiers in Medicine ◽

10.3389/fmed.2021.711034 ◽

2021 ◽

Vol 8 ◽

Author(s):

Martina Gaggl ◽

Alexandra Repitz ◽

Sonja Riesenhuber ◽

Christof Aigner ◽

Christopher Sliber ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Ambulatory Blood Pressure ◽

Controlled Trial ◽

High Dose ◽

Arterial Blood ◽

Oral Sodium

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).

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Effect of oral sodium bicarbonate supplementation on progression of chronic kidney disease in patients with chronic metabolic acidosis: study protocol for a randomized controlled trial (SoBic-Study)

Trials ◽

10.1186/1745-6215-14-196 ◽

2013 ◽

Vol 14 (1) ◽

pp. 196 ◽

Cited By ~ 17

Author(s):

Martina Gaggl ◽

Daniel Cejka ◽

Max Plischke ◽

Georg Heinze ◽

Melanie Fraunschiel ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Randomized Controlled Trial ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Study Protocol ◽

Controlled Trial ◽

Chronic Metabolic Acidosis ◽

Randomized Controlled ◽

Oral Sodium

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Oral Sodium Bicarbonate Supplementation Does Not Affect Serum Calcification Propensity in Patients with Chronic Kidney Disease and Chronic Metabolic Acidosis

Kidney & Blood Pressure Research ◽

10.1159/000498975 ◽

2019 ◽

Vol 44 (2) ◽

pp. 188-199 ◽

Cited By ~ 3

Author(s):

Christof Aigner ◽

Daniel Cejka ◽

Christopher Sliber ◽

Melanie Fraunschiel ◽

Gere Sunder-Plassmann ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Intervention Group ◽

Study Cohort ◽

Serum Bicarbonate ◽

Chronic Metabolic Acidosis ◽

The Mean ◽

Oral Sodium

Background: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and metabolic acidosis might accelerate vascular calcification. The T50 calcification inhibition test (T50-test) is a global functional test analyzing the overall propensity of calcification in serum, and low T50-time is associated with progressive aortic stiffening and with all-cause mortality in non-dialysis CKD, dialysis, and transplant patients. Low serum bicarbonate is associated with a short T50-time and alkali supplementation could be a simple modifier of calcification propensity. The aim of this study was to investigate the short-term effect of oral sodium bicarbonate supplementation on T50-time in CKD patients. Material and Methods: The SoBic-study is an ongoing randomized-controlled trial in CKD-G3 and G4 patients with chronic metabolic acidosis (serum HCO3– ≤21 mmol/L), in which patients are randomized to either achieve serum HCO3– levels of 24 ± 1 mmol/L (intervention group) or 20 ± 1 mmol/L (rescue group). The effect of bicarbonate treatment on T50-time was assessed. Results: The study cohort consisted of 35 (14 female) patients aged 57 (±15) years, and 18 were randomized to the intervention group. The mean T50-time was 275 (± 64) min. After 4 weeks, the mean change of T50-time was 4 (±69) min in the intervention group and 18 min (±56) in the rescue group (β = –25; 95% CI: –71 to 22; p = 0.298). Moreover, change of serum bicarbonate in individual patients was not associated with change in T50-time, analyzed by regression analysis. Change of serum phosphate had a significant impact on change of T50-time (β = –145; 95% CI: –237 to –52). Conclusion: Oral sodium bicarbonate supplementation showed no effect on T50-time in acidotic CKD patients.

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Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: a pilot study

BMC Nephrology ◽

10.1186/s12882-016-0331-6 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 5

Author(s):

Wei Chen ◽

Michal L. Melamed ◽

Thomas H. Hostetter ◽

Carolyn Bauer ◽

Amanda C. Raff ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Pilot Study ◽

Growth Factor ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth ◽

Oral Sodium

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Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm8020208 ◽

2019 ◽

Vol 8 (2) ◽

pp. 208 ◽

Cited By ~ 8

Author(s):

May Khei Hu ◽

Miles D. Witham ◽

Roy L. Soiza

Keyword(s):

Systematic Review ◽

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

Controlled Trials ◽

Bicarbonate Therapy ◽

Randomised Controlled

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

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Effectiveness of a Feed Supplement in Advanced Stages of Feline Chronic Kidney Disease

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.81082 ◽

2018 ◽

Vol 44 (1) ◽

pp. 8

Author(s):

Diana Vergnano ◽

Emanuela Valle ◽

Natascia Bruni ◽

Rita Rizzi ◽

Mauro Bigliati ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Calcium Carbonate ◽

Kidney Disease ◽

Sodium Bicarbonate ◽

Calcium Lactate ◽

Phosphate Binders ◽

Feed Supplement ◽

Normal Range ◽

Renal Diet

Background: Chronic kidney disease (CKD) is a very common pathology in cats, especially in the geriatric age. A proper renal diet is considered the current standard of care to enhance patients’ long-term survival and quality of life. However, when diet alone is not sufficient, it is necessary to supplement it with specific substances: these are phosphate binders and alkalinizing agents. The aim of this study was to evaluate the effectiveness of a feed supplement containing calcium carbonate, calcium lactate gluconate, chitosan and sodium bicarbonate in controlling hyperphosphatemia and metabolic acidosis in cats with severe CKD (IRIS, International Renal Interest Society, stage 3 and 4).Materials, Methods & Results: 10 cats (median BW 4.00 (3.20; 5.70) Kg, BCS 3/5 (2.25; 3.75), 11 (8.25;12.00) years) fed with a balanced renal diet were included in the study. To be enrolled in the study cats had to be affected by CKD in stages 3 or 4 and show hyperphosphatemia. Treatment consisted in oral administration of the product (Renal, Candioli Pharma) at 0.2 g/kg/day mixed with the food for 60 days. The animals were evaluated at the beginning of the study and at 15, 30, 60 days (T0, T15, T30, T60) for: clinical condition, BW, BCS, blood pressure and for routinely hematochemical, biochemical and urinary parameters. Owners were asked to assess appetite of the cat, palatability of the supplement, presence of vomit and/or diarrhoea, general health and vitality. All statistical analyses were performed using SAS software. After checking normality data were analyzed using Kruskal-Wallis and Wilcoxon tests. Results are expressed as median (interquartile range). For the parameters P (P < 0.0001), iCa (P = 0.0008) and HCO3 (P = 0.0002) there were statistically significant differences among times of supplementation (T0, T15, T30, T60). Statistically significant reduction of serum phosphorus concentration was obtained through the study (reduction of 59% at T60 vs T0). Also a statistically significant increase of bicarbonate was seen (7% from T0 to T60). At T60 was also recorded an increase of ionized calcium level, which however was in normal range. For the other laboratory parameters, no statistical difference was recorded. All the owners reported a good palatability of the product. The decrease of vomit and diarrhea episodes and the increase of the appetite reported were statistically significant (P < 0.05).Discussion: The restriction of available dietary phosphorus is now recognised as one of the major contributors in slowing the disease progression and improving survival rates. Phosphate binders are able to absorb phosphate (P) in the intestine, forming insoluble products that are eliminated with the faeces, thus decreasing serum phosphate levels. The phosphate binders contained in the product tested in the present trial were chitosan, calcium lactate gluconate and calcium carbonate. During the study P decreased significantly from T0 to T60, reaching the target post-treatment plasma P concentration for IRIS stage 3 after 30 days. Another important recommendation for CKD treatment is to use alkalinisation therapy if metabolic acidosis is present. The feed supplement tested in this study also contained sodium bicarbonate. In our study, 90% of the patients at the inclusion examination had metabolic acidosis. At the end of the study, the median blood bicarbonate concentration was in the normal range, thus reaching the IRIS treatment target. The feed supplement tested was therefore effective in reducing blood phosphate levels and in increasing blood bicarbonate levels, thus improving the cats’ clinical conditions for the duration of the study without any adverse effect.

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