C - REACTIVE PROTEIN AND ITS ASSOCIATION WITH SERUM URIC ACID AND BICARBONATE LEVEL IN COPD

AIM: The study was planned to evaluate the association of C - reactive protein with Serum Uric Acid and Bicarbonate Level in COPD. MATERIAL AND METHODS: In the present study total 100 (n=100) patients diagnosed for COPD, were enrolled for the study. Patients with neoplastic pathologies, pneumonia and Liver or renal diseases, pregnant and lactating females were excluded from the study. RESULT: The mean level of Serum Bicarbonate, C-reactive protein and uric acid were signicantly higher in COPD patients. A signicant association was observed (p ≤ 0.0001). CONCLUSION: In the present study higher bicarbonate levels that could be the individual biomarker which can assess the respiratory acidosis and CRP and Uric Acid levels judges the severity the disease.

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

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 <22, 22–26, 26.1–29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <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 < 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.

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

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.

Low Serum Bicarbonate and CKD Progression in Children

Background and objectivesStudies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study.Design, setting, participants, & measurementsThe relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy.ResultsSix hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19–22 meq/L were 1.28 [95% confidence interval (95% CI), 0.84 to 1.94] and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19–22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L).ConclusionsIn children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy’s effect in patients with pediatric CKD are needed.

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

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 &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 &lt;88% at 238.2 minutes versus 65.5 minutes (p &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

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

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.

Predicting Prolonged Intensive Care Unit Stay Among Patients With Sepsis-Induced Hypotension

Background Sepsis risk stratification tools typically predict mortality, although stays in the intensive care unit (ICU) of 24 hours or longer may be more clinically relevant for emergency department disposition. Objective To explore predictors of ICU stay of 24 hours or longer among infected, hypotensive emergency department patients. Methods A secondary analysis of 2 prospective, observational studies of adult patients with severe sepsis or an infection with a systolic blood pressure less than 90 mm Hg in 3 urban, academic emergency departments was performed. Patients with hypotension and infection were included. Patients with emergency department intubation, vasopressor administration, and/or death were excluded. The primary outcome was ICU stay of 24 hours or longer or death in less than 24 hours. Multivariable logistic regression was used to predict ICU stay of 24 hours or longer. Results Of 233 patients, 108 (46.4%) had ICU stays of 24 hours or longer. History of heart failure (odds ratio, 3.6; 95% CI, 1.5-8.3), bicarbonate level less than 20 mEq/L (odds ratio, 2.0; 95% CI, 1.1-3.8), respiratory rate greater than 20/min (odds ratio, 2.0; 95% CI, 1.1-3.7), and creatinine level greater than 2.0 mg/dL (odds ratio, 3.6; 95% CI, 1.9-6.7) were independent predictors of ICU stay of 24 hours or longer (area under curve, 0.74). The presence of 1 of these factors predicted ICU stay of 24 hours or longer (area under curve, 0.74) with 82.4% sensitivity and 49.6% specificity. Conclusions These exploratory results show that heart failure, bicarbonate level of less than 20 mEq/L, tachypnea, or creatinine level greater than 2.0 mg/dL increases the likelihood of an ICU stay of 24 hours or longer among infected, hypotensive emergency department patients.

Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial

Background Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level. Methods The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target &lt;120 mmHg (intensive treatment) or &lt;140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants (ClinicalTrials.gov: NCT01206062). Results Over a median follow-up of 3.33 years (interquartile range 2.87–3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate &lt;22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11–2.14, P = 0.01), compared with participants with bicarbonate 22–26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97). Conclusions In hypertensive individuals, serum bicarbonate level &lt;22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.