MO021GALECTIN 3 LEVEL IS REDUCED BY TREATMENT WITH SODIUM BICARBONATE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mirela Dobre ◽  
Neil Patel ◽  
Hima Sapa ◽  
Edward Horwitz ◽  
Michal Melamed ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Placebo Group ◽  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Myocardial Fibrosis ◽  
Bicarbonate Level ◽  
Serum Bicarbonate ◽  
Galectin 3 ◽  
Serum Bicarbonate Level ◽  
One Year

Abstract Background and Aims Circulating cardiac biomarkers implicated in the pathogenesis of heart disease are a non-invasive platform to assess the cardiovascular disease (CVD) burden in individuals with chronic kidney disease (CKD). Galectin 3 is a 26 kDa β-galactoside-binding lectin that has a graded and positive association with CKD stages. In animal models, inhibition of galectin-3 prevents myocardial fibrosis. These pre-clinical findings have not been replicated in randomized controlled studies in humans. Metabolic acidosis of CKD has been shown to be associated with adverse CVD outcomes. We sought to examine whether correction of metabolic acidosis of CKD leads to lower circulating levels of Galectin 3, as an expression of myocardial fibrosis. Method A total of 95 participants with stages 3 and 4 CKD and a serum bicarbonate level between 21-25 mEq/L, were randomized to receive sodium bicarbonate at a dose of 0.4 mEq/kg/day once a day or placebo for two years at two clinical sites in US. Galectin 3, was measured at study baseline and after one year. Results Fifty participants were randomized to sodium bicarbonate and 45 to placebo. Mean age (SD) was 61.4 (10.2) years, 48% were women, 57% were non-Hispanic black, and 40% were non-Hispanic white, 61% had diabetes mellitus and 90% had hypertension at baseline. Mean baseline serum bicarbonate level was 23.5 (SD 1.7), mean (SD) baseline eGFR was 38.8 (11.2) ml/min/1.7m2 and mean (SD) baseline systolic BP was 130 (17) mmHg. There were no differences in baseline characteristics between treatment groups. Compared to the placebo group, participants randomized to sodium bicarbonate had statistically significant change in the levels of Galectin 3 after one year of treatment (-7.12% vs 7.76% and -1.25 vs 1.54 ng/ml, p=0.03 in the sodium bicarbonate vs. placebo group, respectively, Figure). In subgroup analyses by CKD stages, participants with stage 3A randomized to sodium bicarbonate observed the highest decrement in Galectin 3 levels (-19.2% vs 14.7%, p=0.01; -3.3% vs -4.8%, p=0.49; and -7.4% vs 29.1%, p=0.09; for CKD 3B, 3B and 4, respectively). Conclusion The level of Galectin 3 was reduced in patients with CKD 3 and 4 treated with sodium bicarbonate. This provides a framework for future therapeutic interventions aimed at reduction of myocardial fibrosis in patients with CKD and metabolic acidosis.

Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients

2019 ◽  
Vol 51 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Piyawan Kittiskulnam ◽  
Somrath Srijaruneruang ◽  
Adhisabandh Chulakadabba ◽  
Nintita Sripaiboonkij Thokanit ◽  
Kearkiat Praditpornsilpa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Muscle Strength ◽  
Sodium Bicarbonate ◽  
Muscle Mass ◽  
Control Group ◽  
Bicarbonate Level ◽  
Serum Bicarbonate ◽  
Serum Bicarbonate Level

Background: Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients. Methods: This was a randomized, controlled study. CKD stage 3–4 patients with serum HCO3– <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate. Results: Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (–3,137.8; 95% CI –6,235.3 to –40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106–156] to 110 [87–144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study. Conclusion: Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study.

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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Donald E Wesson ◽  
Vandana Mathur ◽  
Navdeep Tangri ◽  
Yuri Stasiv ◽  
Dawn Parsell ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Placebo Group ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Physical Function ◽  
Dose Titration ◽  
Serum Bicarbonate ◽  
Chair Stand ◽  
Stand Test ◽  
Chair Stand Test

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. &gt;300 mg/g are shown in the Table. Neither albuminuria (log UACR) as a continuous covariate nor the presence of UACR &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 &gt;0.4). In patients with UACR &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 &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.

scholarly journals Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results

2021 ◽  
Vol 8 ◽  
Author(s):  
Hyo Jin Kim ◽  
Hyunjin Ryu ◽  
Eunjeong Kang ◽  
Minjung Kang ◽  
Miyeun Han ◽  
...  
Keyword(s):  
Risk Factor ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Rapid Decline ◽  
Bicarbonate Level ◽  
Serum Bicarbonate ◽  
Serum Bicarbonate Level ◽  
Renal Progression

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients.Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide &lt;22, 22–26, 26.1–29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level &lt;22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope.Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01–1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39–3.22, P &lt; 0.001] compared to the lower normal bicarbonate group.Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.

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

2019 ◽  
Vol 44 (2) ◽  
pp. 188-199 ◽  
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.

scholarly journals Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
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.

Is Serum Bicarbonate Level Associated With Negative Outcomes in Pediatric Patients?

2017 ◽  
Vol 33 (11) ◽  
pp. e108-e113
Author(s):  
Naveen Poonai ◽  
David Mainprize ◽  
Carolyn Travers ◽  
Lilian Lee Yan Vivas ◽  
Peter Tryphonopoulos ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Bicarbonate Level ◽  
Serum Bicarbonate ◽  
Negative Outcomes ◽  
Serum Bicarbonate Level

scholarly journals Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults

2018 ◽  
Vol 13 (4) ◽  
pp. 596-603 ◽  
Author(s):  
Mirela Dobre ◽  
Sarah A. Gaussoin ◽  
Jeffrey T. Bates ◽  
Michel B. Chonchol ◽  
Debbie L. Cohen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Executive Function ◽  
Metabolic Acidosis ◽  
Cognitive Function ◽  
Magnetic Resonance ◽  
Bicarbonate Level ◽  
Serum Bicarbonate ◽  
Resonance Imaging ◽  
Bicarbonate Concentration ◽  
Link Type

Background and objectivesCognitive function worsens as kidney function declines, but mechanisms contributing to this association are not completely understood. Metabolic acidosis, a common complication of CKD, leads to neural networks overexcitation and is involved in cerebral autoregulation. We aimed to evaluate the association between serum bicarbonate concentration as a measure of metabolic acidosis, and cognitive function in hypertensive adults with and without CKD.Design, setting, participants, & measurementsFive cognitive summary scores were measured (global cognitive function, executive function, memory, attention/concentration, and language) in 2853 participants in the Systolic BP Intervention Trial (SPRINT). Multivariable linear regression models adjusted for demographics, comorbidities, systolic BP, medications, eGFR and albuminuria evaluated the cross-sectional association between bicarbonate and cognition at SPRINT baseline. In a subset (n=681) who underwent brain magnetic resonance imaging, the models were adjusted for white matter hyperintensity volume, vascular reactivity, and cerebral blood flow.ResultsThe mean age (SD) was 68 (8.5) years. Global cognitive and executive functions were positively associated with serum bicarbonate (estimate [SEM]: 0.014 [0.006]; P=0.01, and 0.018 [0.006]; P=0.003, respectively). Each 1 mEq/L lower bicarbonate level had a similar association with global cognitive and executive function as being 4.3 and 5.4 months older, respectively. The association with global cognition persisted after magnetic resonance imaging findings adjustment (estimate [SEM]: 0.03 [0.01]; P=0.01). There was no association between serum bicarbonate level and memory, attention/concentration, and language.ConclusionsIn a large cohort of hypertensive adults, higher serum bicarbonate levels were independently associated with better global cognitive and executive performance. (ClinicalTrials.gov: NCT01206062).

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