Higher Serum Bicarbonate Level Research Articles

Association of Serum Bicarbonate Level with Mortality in Patients with Acute Kidney Injury: A Retrospective Cohort Study

ABSTRACT Background: Metabolic acidosis due to a decreased level of serum bicarbonate in patients with chronic kidney disease is associated with increased mortality, but the association of serum bicarbonate with outcomes in patients with acute kidney injury (AKI) is uncertain. We investigated the association of serum bicarbonate level with mortality in patients with AKI. Methods: The study cohort consisted of 4800 patients diagnosed with AKI at multiple hospitals between September 17, 2013, and April 14, 2014. Smooth curve fitting, threshold effect analysis, and multiple regression analysis were used to assess the relationship between serum bicarbonate and 14-day mortality (primary outcome) and with intensive care unit (ICU) admission, length of hospitalization, and total hospital costs (secondary outcomes). Results: Multiple regression analysis, adjusting for confounding factors, demonstrated a U-shaped association between serum bicarbonate levels and AKI mortality. The lowest mortality rate was observed in patients with a bicarbonate level of 26.9 mmol/L, while greater rates were observed in those with lower and higher levels. Additionally, patients with AKI exhibiting high serum bicarbonate levels (> 26.9 mmol/L) had a significantly lower rate of ICU admission and a shorter hospital stay compared to those with low serum bicarbonate levels (< 26.9 mmol/L). Conclusion: A serum bicarbonate level of 26–29 mmol/L in patients with AKI is associated with a lower 14-day mortality rate, with the lowest rate observed at a serum bicarbonate level of 26.9 mmol/L. Prospective clinical studies are needed to determine whether optimizing the serum bicarbonate level can decrease mortality in this population.

Serum bicarbonate levels and kidney outcomes in critically ill patients: a prospective cohort study.

The interplay between serum bicarbonate levels and kidney outcomesis not fully understood. We conducted a prospective cohort study in three intensive care units (ICUs) to evaluate the association of serum bicarbonate levels with acute kidney injury (AKI) and kidney function recovery in critically ill patients. A prospective cohort study in three intensive care units (ICUs) was performed. The serum bicarbonate level in the first 24h after ICU admission was categorized as low (< 22mEq/L), normal (22-26mEq/L), or high (> 26mEq/L). Serum creatinine (SCr) levels according to theKDIGOAKI guideline were used for defining AKIwithin the first 7 days of ICU stay. At ICU admission, SCr≥ 1.1for women and ≥ 1.3 mg/dL for men were indicative of impaired kidney function.Mortality outcome was tracked up to 28days, and kidney function recovery was assessed at hospital discharge. A total of 2732 patients (66 ± 19years and 55% men) were analyzed, with 32% having impaired kidney functionat ICU admission. Overall, 26% of patients had low bicarbonate levels, while 32% had high bicarbonate levels. Notably, patients with preserved kidney function showed a lower prevalence of low bicarbonate levels compared to those with impaired kidney function (20% vs. 39%, p < 0.001), while higher rates were observed for high bicarbonate (35% vs. 24%, p < 0.001). Compared with patients with normal serum bicarbonate levels, those with low bicarbonate were 81% more likely to develop AKI (OR = 1.81; 95% CI 1.10-2.99), whereas those with high bicarbonate were 44% less likely (OR = 0.56; 95% CI 0.32-0.98) in the adjusted model for confounders. Neither those with high nor low serum bicarbonate levels were associated with an increased risk of mortality (HR = 1.03; 95% CI 0.68-1.56 and 0.99; 95% CI 0.68-1.42, respectively). In subgroup analysis, regardless of the kidney functionat ICU admission, serum bicarbonate levels were not associated with the development of AKI and all-cause mortality. Regarding kidney function recovery, higher non-recovery rates were found for those with low bicarbonate. In critically ill ICU patients, low bicarbonate levels were associated with the more likely development of AKIand subsequentnon-recovery ofkidney function, while high bicarbonatelevels showed no such association. Therefore, low bicarbonate levels may be considered a risk factor for adverse kidney outcomes in critically ill patients.

Association Between Serum Bicarbonate Levels and Prediabetes and Subclinical Inflammation in Young Healthy Adults: A Cross-sectional Study.

Low bicarbonate, a hallmark of metabolic acidosis is associated with various diseases. This study investigated associations between bicarbonate levels with prediabetes and subclinical inflammation among healthy young adults in Qatar. A cross-sectional study was carried out with 825 participants aged 18-40 years, devoid of any known comorbidities, using data from the Qatar Biobank. For each participant, blood samples were taken for measurements of bicarbonate, prediabetes, and subclinical inflammation biomarkers. Prediabetes was defined using HbA1c between 5.7 and 6.4% and subclinical inflammation was defined using monocyte to high density lipoprotein (HDL) cholesterol ratio (MHR). Associations between bicarbonate levels and the outcomes were analyzed using multivariable linear and logistic regression and then stratified by gender. A total of 825 participants with mean age 29.2 years (5.9) of which 365 (44.2%) were males. After multivariable logistic regression, each unit increase in serum bicarbonate was associated with a 17% decreased risk of prediabetes (OR: 0.83, 95%CI: 0.70-0.99, p=0.034), in males but no association was observed for females. Similarly, after multivariable linear regression, a unit increase in serum bicarbonate was associated with a 0.18 unit decrease in MHR (beta -0.18, 95%CI: -0.29, -0.07, p=0.002), again with no association observed in females. In a healthy young adult population, higher serum bicarbonate levels were inversely associated with both prediabetes and subclinical inflammation in males, but not in females.

No Good Deed: Acidosis in Chronic Kidney and Liver Disease

Studies have shown that low or high serum bicarbonate levels (reflecting metabolic acidosis or alkalosis)are associated with increased all-cause mortality rates in moderate and advanced chronic kidney disease (CKD) cases. Correction of presumed acidosis using sodium bicarbonate, targeting serum levels around 22 mmol/l, has proven beneficial in delaying the progression of the disease and provided mortality benefit. A similar prognostic association may exist between uncorrected metabolic acidosis in chronic liver disease. Correcting it with sodium-containing salts may require more interventions due to increased sodium/fluid load. In patients with liver failure, a naturally alkalotic state, where sodium load is a concern, the impact of this intervention is unclear. This study aims to generate proof of concept through a retrospective chart review in individuals with CKD-related metabolic acidosis and liver cirrhosis. We extrapolate that lowering bicarbonate targets in other clinical scenarios like liver failure, pregnancy, and cardiac failure may be prudent and will lead to a lower sodium load.

Post-Hypercapnic Alkalosis: A Brief Review.

Metabolic alkalosis is a common acid-base imbalance frequently observed in intensive care unit (ICU) patients and is associated with increased mortality. Post-hypercarbia alkalosis (PHA) is a type of metabolic alkalosis caused by sustained high serum bicarbonate levels following a rapid resolution of hypoventilation in patients with chronic hypercapnia due to prolonged respiratory disturbance. Common causes of chronic hypercapnia include chronic obstructive pulmonary disease (COPD), central nervous system disorders, neuromuscular disorders, and narcotic abuse. Rapid correction of hypercapnia through hyperventilation leads to a swift normalization of pCO2, which lacks renal compensation, consequently causing an increase in plasma HCO3- levels and severe metabolic alkalosis. Most of PHA occurs in the ICU setting requiring mechanical ventilation and can progress severe alkalemia due to secondary mineralocorticoid excess from volume depletion or decreased HCO3- excretion from decreased glomerular filtration rate and increased proximal tubular reabsorption. PHA is associated with increased ICU stay, ventilator dependency, and mortality. Acetazolamide, a carbonic anhydrase inhibitor, has been utilized for managing PHA by inducing alkaline diuresis and reducing tubular reabsorption of bicarbonate. While acetazolamide effectively improves alkalemia, its impact on hard outcomes may be limited by factors such as patient complexity, co-administered medications, and underlying conditions contributing to alkalosis.

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.

Association of serum bicarbonate with graft survival and mortality in kidney transplant recipients.

Metabolic acidosis is an independent risk factor for kidney disease progression with a high prevalence after kidney transplantation (KTx). Remarkably, it is still unclear if there is an impact of metabolic acidosis on graft function and death after KTx. Thus, we wanted to investigate if serum bicarbonate is associated with long-term graft outcome and mortality after KTx. We performed a single-center retrospective study including adult de novo KTx patients between 1999 and 2015. Cox proportional hazard model was used to analyze a possible association between time-dependent serum bicarbonate measurements and graft failure or death. Four hundred thirty KTRs were included in the analysis with a mean age of 50.9 ± 13.4years. Mean observation time was 4.7 ± 2.8years. Two hundred eighty-four (66%) patients were male and 318 (74%) had received a deceased donor kidney transplant. Mean bicarbonate and eGFR levels 1 year post-transplant amounted to 22.9 ± 3.1mEq/L and 61 ± 26ml/min/1.73 m2, respectively. Prevalence of metabolic acidosis was 31% 1 year after transplantation. Fourteen (3%) patients died and 31 (7%) suffered from graft failure. Higher bicarbonate levels were associated with significantly lower hazards for graft failure (Hazard Ratio (HR) = 0.88; 95% Confidence Interval (CI): 0.79-0.98) and mortality (HR = 0.79; 95% CI 0.66-0.93) after adjusting for potential confounders such as age, donor type and time-varying eGFR. Our analysis showed that higher serum bicarbonate levels are positively associated with long-term graft and patient survival in kidney transplant recipients. Thus, serum bicarbonate may serve as a predictor and independent risk factor for graft and patient outcome after KTx as has been previously shown for patients with CKD.

Complications and Outcomes in Patients With Diabetic Ketoacidosis and COVID19

Introduction: COVID-19 infection caused by the novel coronavirus SARS-CoV-2 has been associated with new-onset diabetes and diabetic ketoacidosis. There are currently limited reports observing the effect of COVID-19 infection on outcomes in patients hospitalized with diabetic ketoacidosis (DKA). Methods: This retrospective study used electronic medical records, between March 1, 2020 to September 14, 2020, and included patients aged ≥ 18 years with DKA. Clinical characteristics, hospital course, and complications (ICD-10 codes) were compared between patients admitted with DKA and confirmed COVID-19 infection (COVID+) to those with DKA without COVID-19 infection (COVID-). The American Diabetes Association criteria was used to define DKA. Results: Among 757 patients with DKA, 80 COVID+ patients with and 677 COVID- patients were included (mean age 49.1 years, female 52.7%, African-American 70.4%). Baseline characteristics were similar between groups. The COVID+ group had a lower admission glucose (mean glucose 413.1 ± 218.7 mg/dL vs 441.1 ± 222.6 mg/dL, p-value 0.05), and higher serum bicarbonate levels (18.2 mmol/L vs 16.6 mmol/L, p-value <0.05) compared to the COVID- group. Compared to the COVID- group, COVID+ required a longer time to achieve blood glucose < 250 mg/dl from admission (8.8 hours vs 7.1 hours, p-value <0.01), and had higher rates of acute respiratory failure (48.8% vs 9.5%, p-value <0.001), mechanical ventilation (32.5% vs 10.9%, p-value <0.001), sepsis (37.5% vs 15.7%, p-value <0.001), acute thrombotic events (11.3% vs 2.7%, p-value <0.05), and pneumonia (70% vs 10.3%, p-value <0.001). COVID+ had higher mortality (16.3% vs 3.1%, p-value < 0.001), ICU length of stay (median 5.5 days or 2–58 days vs median 2 days or 2–123 days, p-value <0.001), and total LOS (median 7.5 or 1–47 days vs median 5 days or 1–98 days, p-value <0.001). Both groups required similar total insulin doses throughout the entire hospitalization (mean 143 +/- (SD) vs 142 +/- SD units, p-value 0.088). Conclusion: Our data shows that COVID-19 infection is associated with increased mortality, worse clinical outcomes, and longer LOS among patients hospitalized with DKA, while presenting with less severe hyperglycemia and acidemia compared to those without COVID-19 infection.

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

0675 Nocturnal Oxygen Supplementation With Positive Airway Pressure Therapy For Obesity Hypoventilation Syndrome: Clinical Predictors And Liberation From Oxygen

Abstract Introduction Obesity hypoventilation syndrome (OHS) is associated with a high morbidity and mortality. Many patients require nocturnal supplemental oxygen on top of positive airway pressure (PAP) therapy for hypoxemia independent of apneic events. We need to clinically identify patients likely to require nocturnal oxygen supplementation. Follow up is essential as with adequate control of sleep apnea, hypoxia improves and liberation from nocturnal oxygen supplementation may be achievable. Methods Researchers obtained a list of patients with coding diagnosis of OHS, seen at the Jefferson Sleep Center between November 2016 and September 2019. Patients with BMI of ≥ 30 and evidence of hypoventilation were included. Hypoventilation was defined as an elevated CO2 level of ≥ 45 mmHg on blood gas analysis, elevated serum bicarbonate level of ≥ 27 mmol/L or by evidence of nocturnal hypoventilation by AASM criteria on polysomnography. Patients with pulmonary and neuromuscular disorders were excluded Results Out of 189 patients reviewed, 36 met the inclusion and exclusion criteria. Nineteen patients (53%) required nocturnal oxygen supplementation. A higher serum bicarbonate level of 33 mmol/L against 30 mmol/L (p=0.0078) and a lower resting awake SaO2 of 89% versus 95% (p &amp;lt;0.01) were observed in the oxygen supplementation group. In polysomnographic data, the oxygen supplementation group had lower SaO2 nadir of 67% versus 73% (p=0.026) and had a longer time with SaO2 &amp;lt;88% at 238.2 minutes versus 65.5 minutes (p &amp;lt;0.01). Nine out of the 19 patients (47%) underwent nocturnal oximetry on PAP and room air. Of these, 4 patients (44%) were liberated from oxygen. Conclusion Fifty three percent of patients with OHS required nocturnal oxygen supplementation on top of PAP therapy. Higher serum bicarbonate level and lower resting awake SaO2 are potential clinical predictors of nocturnal oxygen supplementation. After nocturnal oximetry on PAP, 44% were successfully liberated from supplemental oxygen. Support

Prevalence and correlates of sleep apnea among US Veterans with chronic kidney disease.

The prevalence and correlates of sleep apnea (SA) among Veterans with chronic kidney disease (CKD), a population at high risk of both SA and CKD, are unknown. We performed a cross-sectional analysis of 248 Veterans (18-89years) selected only for presence of moderate to severe CKD. All participants underwent full, unattended polysomnography, measurement of renal function and a sleepiness questionnaire. Logistic regression with backward selection was used to identify predictors of prevalent SA (apnea-hypopnea index [AHI, ≥15events/hr] and prevalent nocturnal hypoxia [NH, % of total sleep time spent at <90% oxygen saturation]). The mean age of our cohort was 73.2±9.6years, 95% were male, 78% were Caucasian and the mean body mass index (BMI) was 30.3±4.8kg/m2 . The prevalence of SA was 39%. There was no difference in daytime sleepiness among those with and without SA. In the final model, older age, higher BMI and diabetes mellitus (DM) were associated with higher odds of SA, after controlling for age, BMI, race and sex. Higher BMI, DM, unemployed/retired status, current smoking and higher serum bicarbonate level were associated with prevalent NH. To sum, SA was common among Veterans with moderate to severe CKD. Although some traditional risk factors for SA were associated with SA in this population, sleepiness did not correlate with SA. Further study is needed to validate our findings and understand how best to address the high burden of SA among Veterans with CKD.

Serum Bicarbonate as a Surrogate for pH in Hemodialysis: A Pilot Study

Rationale & ObjectiveExcess morbidity and mortality are associated with both high and low serum bicarbonate levels in epidemiologic studies of patients with end-stage kidney disease (ESKD) receiving hemodialysis. The Kidney Disease Outcomes Quality Initiative (KDOQI) recommends modifying dialysate bicarbonate concentration to achieve a predialysis serum bicarbonate level ≥ 22 mmol/L, measured as total carbon dioxide (CO2). This practice assumes that total CO2 is an adequate surrogate for acid-base status, yet its surrogacy performance is unknown in ESKD. We determined acid-base status at the beginning and end of hemodialysis using total CO2 and pH and tested whether total CO2 is an appropriate surrogate for acid-base status.Study DesignPilot study.Setting & Participants25 veterans with ESKD receiving outpatient hemodialysis.Tests ComparedpH, calculated bicarbonate level, and total CO2.OutcomesThe proportion of paired samples for which total CO2 misclassified acid-base status according to pH was determined. Bias of total CO2 was evaluated using Bland-Altman plots, comparing it to calculated bicarbonate.ResultsAmong 71 samples, mean pH was 7.41 ± 0.03 predialysis and 7.48 ± 0.05 postdialysis. Compared with interpretation of full blood gas profiles, 9 of 25 (36%) participants were misclassified as acidemic using predialysis total CO2 measures alone (total CO2 < 22 mmol/L but pH ≥ 7.38); 1 (4%) participant was misclassified as alkalemic (total CO2 > 26 mmol/L but pH ≤ 7.42). Among paired samples in which predialysis total CO2 was < 22 mmol/L, the corresponding pH was acidemic (< 7.38) in just 3 of 13 (23%) instances.LimitationsSmall, single-center, entirely male cohort.ConclusionsA majority of participants became alkalemic during routine hemodialysis despite arriving with normal pH. 10 of 25 (40%) participants’ acid-base status was misclassified using total CO2 measurements alone; the majority of predialysis total CO2 values that would trigger therapeutic modification according to practice guidelines did not have acidemia when assessed using pH. Efforts to improve dialysis prescription require recognition that total CO2 may not be reliable for interpreting acid-base status in hemodialysis patients.

Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults.

Cognitive 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. Five 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. The 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. In a large cohort of hypertensive adults, higher serum bicarbonate levels were independently associated with better global cognitive and executive performance. (ClinicalTrials.gov: NCT01206062).

Low-protein diet for conservative management of chronic kidney disease: a systematic review and meta-analysis of controlled trials.

BackgroundRecent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low‐protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein‐energy wasting or cachexia. We aimed to systematically review and meta‐analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low‐protein diet in the management of uraemia and its complications in patients with CKD.MethodsWe searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta‐analyses.ResultsWe identified 16 controlled trials of low‐protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of >0.8 g/kg/day, diets with restricted protein intake (<0.8 g/kg/day) were associated with higher serum bicarbonate levels, lower phosphorus levels, lower azotemia, lower rates of progression to end‐stage renal disease, and a trend towards lower rates of all‐cause death. In addition, very‐low‐protein diets (protein intake <0.4 g/kg/day) were associated with greater preservation of kidney function and reduction in the rate of progression to end‐stage renal disease. Safety and adherence to a low‐protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein‐energy wasting.ConclusionsIn this pooled analysis of moderate‐size controlled trials, a low‐protein diet appears to enhance the conservative management of non‐dialysis‐dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein‐energy wasting and cachexia remains minimal.

Bicarbonate Balance and Prescription in ESRD.

The optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.

Moderator's view: Higher serum bicarbonate in dialysis patients is protective.

Several observational studies have reported an association between higher serum bicarbonate level and high mortality risk in dialysis patients. However, in such studies mere discovery of associations does not allow one to infer causal relationships. This association may be related to inadequate dietary protein intake that may lead to less acid generation and hence a higher serum bicarbonate level. Since undernutrition is a strong predictor of death in hemodialysis patients, the observed association may be an epiphenomenon and not a biologically plausible relationship. Higher protein and fluid intake between two subsequent hemodialysis treatments may lead to lower serum bicarbonate level. This low bicarbonate level may appear protective, as patients with higher food intake and better appetite generally exhibit greater survival. In the contemporary three-stream proportioning system of hemodialysis treatment, the bicarbonate concentrate is separate from the acid concentrate, and the contribution of the acid concentrate organic acid (acetate, citrate or diacetate) to the delivered bicarbonate pool of the patient is negligible. The concept of 'total buffer' that assumes that the combination of bicarbonate and acetate concentrations in the dialysate are added equally as bicarbonate equivalents is likely wrong and based on the misleading notion that the acetate of the acid concentrate is fully metabolized to bicarbonate in the dialysate. Given these uncertainties it is prudent to avoid excessively high or low bicarbonate levels in dialysis patients.

The impact of high serum bicarbonate levels on mortality in hemodialysis patients.

Background/AimsThe optimal serum bicarbonate level is controversial for patients who are undergoing hemodialysis (HD). In this study, we analyzed the impact of serum bicarbonate levels on mortality among HD patients.MethodsPrevalent HD patients were selected from the Clinical Research Center registry for End Stage Renal Disease cohort in Korea. Patients were categorized into quartiles according to their total carbon dioxide (tCO2) levels: quartile 1, a tCO2 of < 19.4 mEq/L; quartile 2, a tCO2 of 19.4 to 21.5 mEq/L; quartile 3, a tCO2 of 21.6 to 23.9 mEq/L; and quartile 4, a tCO2 of ≥ 24 mEq/L. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) and confidence interval (CI) for mortality.ResultsWe included 1,159 prevalent HD patients, with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from quartile 4, compared to those from the other quartiles (p = 0.009, log-rank test). The multivariate Cox proportional hazard model revealed that patients from quartile 4 had significantly higher risk of mortality than those from quartile 1, 2 and 3, after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to 3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04).ConclusionsOur data indicate that high serum bicarbonate levels (a tCO2 of ≥ 24 mEq/L) were associated with increased mortality among prevalent HD patients. Further effort might be necessary in finding the cause and correcting metabolic alkalosis in the chronic HD patients with high serum bicarbonate levels.

Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

BackgroundMetabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression.MethodsOne hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome.ResultsFemale patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914].ConclusionsIn elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan-Meier survival curves, and time-dependent analysis. Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.