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.

Evaluation of Early Administration of Insulin Glargine in the Acute Management of Diabetic Ketoacidosis

Background: Few studies have evaluated the early use of insulin glargine in the management of diabetic ketoacidosis (DKA) patients. Early insulin glargine use in DKA was safe and associated with a trend towards faster DKA resolution. Objectives: To evaluate the efficacy and safety of early insulin glargine administration for acute management of DKA in critically ill patients. Methods: This single-center retrospective cohort study included patients, who were >18 years of age with DKA, admitted to the intensive care unit (ICU) for at least 12 h, and received intravenous insulin infusion for at least 6 h. The primary endpoint was the association between the time to insulin glargine administration and time to DKA resolution. Linear and logistic regression analyses were performed. Results: Of the 913 patients evaluated, 380 were included in the study. The overall mean age was 45±17 years, 196 (51.6%) were female, and 262 (70%) patients had type 1 diabetes mellitus. The mean blood glucose level was 584.9±210 mg/dL, pH was 7.16±0.17, anion gap was 28.17±6.9 mEq/L, and serum bicarbonate level was 11.19±5.72 mEq/L. Every 6-h delay in insulin glargine administration was associated with a 26-min increase in time to DKA resolution (95% confidence interval [CI], 14.76–37.44; p<0.0001), 3.2-h increase in insulin infusion duration (95% CI, 28.8–36; p<0.0001), and 6.5-h increase in ICU LOS (95% CI, 5.04–7.92; p<0.0001). Conclusion: Early administration of insulin glargine is potentially safe and may be associated with a reduction in time to DKA resolution and shorter duration of insulin infusion.

T2 Weighted Hypointense Subcortical White Matter- A Rare Imaging Feature in Ketotic Hyperglycaemia

Diabetic ketoacidosis is a hyperglycaemic state in which serum glucose level is more than 250 mg/dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq/L, and serum ketone level is raised and dehydration is present. Insulin deficiency is the main precipitating factor. Rarely, they present with neurological complications such as focal/generalised motor seizures, hemiparesis and sensory deficits which may be associated with various imaging features. With increasing prevalence of diabetes in the last decade, it is vital to familiarise with various hyperglycaemia induced imaging abnormalities in brain in order to provide accurate diagnosis for providing prompt treatment and preventing complications. T2W/FLAIR (Fluid-attenuated inversion recovery) subcortical hypointensity in ketotic patients presenting with focal seizures had been reported rarely. Here, presented are imaging findings of a 27-year-old female patient with newly diagnosed type II diabetes mellitus and diabetic ketoacidosis with new onset seizures. T2 subcortical white matter hypointensity was noted in the right post-central gyrus. Though non specific, this imaging finding was of importance in such cases of hyperglycaemia in order to formulate further patient care.

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.

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.

1481. A Study for Risk Factors of Acute Kidney Injury in Leptospirosis in a Tertiary Health Center in South India

Background Leptospirosis is the most widespread zoonotic disease in the world. In India, it is endemic in coast lined states. Renal failure is a severe complication with mortality approaching 22%, early recognition of which helps clinicians in acting fast. This study aimed to investigate the predictors of Acute Kidney Injury (AKI) in Leptospirosis Methods This is a prospective, case–control study done in a tertiary care center in Southern India carried out between October 2017 and December 2018. Patients with confirmed Leptospirosis as per CDC 2013 and Faine’s criteria (2012) having AKI as per KDIGO criteria were defined as cases. Subjects without AKI were controls. Demographic, clinical and laboratory data were compared between the groups and analyzed. Logistic regression was performed to analyze the possible risk factors associated with AKI in Leptospirosis. Results A total of 329 subjects met the inclusion criteria of the study. 187 patients with AKI (CASES) and 142 patients without AKI (CONTROLS) were studied. Patients with AKI were older, (mean age- 46.99 ± 13.21 vs. 42.99 ± 15.15 years) had longer hospital stay (9.04 ± 5.62 vs. 6.27 ± 3.27 days) had higher SOFA (7.97 ±2.9 vs. 3.37 ± 2.6) and APACHE 2 scores (14.37±5.93 vs. 4.66 ± 4.4), lower mean arterial pressure (84.01 ± 14.45 vs. 89.01 ± 10.63 mmHg; P = 0.001) lower serum bicarbonate level (21.70 ± 2.35 vs. 18.73 ± 3.78 mEq/dL; P < 0.001). Factors like serum lactate, AST, ALT had no significant difference between the groups. Serovar identification was done in 88 patients, of which 57 had AKI. Australis (16.7%), Pyrogenes (16.7%) and Grippotyphosa (11.1%) were the commonest serovars isolated. Serovar most commonly associated with AKI was Pyrogenes (17.5%) Predictors for AKI were jaundice (P = 0.01, OR 2.25; CI 1.21 –3.26), vomiting (P = 0.017, OR 1.9, CI 1.12- 3.26) Hypotension (P = 0.02, OR = 12.3, CI 1.85 – 107.2), tachypnea (P = 0.006, OR = 2.55, CI 1.11- 3.24), leukocytosis (P < 0.001, OR 5.45, CI 1.86- 4.89), thrombocytopenia (P < 0.001, OR 6.49, CI 2.33 – 6.75) Conclusion Identification of features like hypotension, tachypnea, acidosis, leukocytosis, thrombocytopenia, the occurrence of serovar Pyrogenes should alert the clinician on risk of developing AKI Disclosures All authors: No reported disclosures.

CLINICAL UTILITY OF RISK SCORES IN VARICEAL BLEEDING

ABSTRACT BACKGROUND: Variceal bleeding remains important cause of upper gastrointestinal bleed. Various risk scores are used in risk stratification for non-variceal bleed. Their utility in variceal bleeding patients is not clear. This study aims to compare probability of these scores in predicting various outcomes in same population. OBJECTIVE: This study aims to compare probability of these scores in predicting various outcomes in same population. To study characteristics and validate AIMS65, Rockall, Glasgow Blatchford score(GBS), Progetto Nazionale Emorragia Digestiva (PNED) score in variceal Upper Gastrointestinal Bleed (UGIB) patients for predicting various outcomes in our population. METHODS: Three hundred subjects with UGIB were screened prospectively. Of these 141 patients with variceal bleeding were assessed with clinical, blood investigations and endoscopy and risk scores were calculated and compared to non-variceal cases. All cases were followed up for 30 days for mortality, rebleeding, requirement of blood transfusion and need of radiological or surgical intervention. RESULTS: Variceal bleeding (141) was more common than non variceal (134) and 25 had negative endoscopy. In variceal group, cirrhosis (85%) was most common etiology. Distribution of age and sex were similar in both groups. Presence of coffee coloured vomitus (P=0.002), painless bleed (P=0.001), edema (P=0.001), ascites (P=0.001), hemoglobin <7.5 gms (P<0.001), pH<7.35 (P<0.001), serum bicarbonate level <17.6 mmol/L (P<0.001), serum albumin<2.75 gms% (P<0.001), platelet count <1.2 lacs/µL (P<0.001), high INR 1.35 (P<0.001), BUN >25mmol/L (P<0.001), and ASA status (P<0.001), high lactate >2.85 mmol/L (P=0.001) were significant. However, no factor was found significant on multivariate analysis. Rockall was found to be significant in predicting mortality and rebleed. AIMS65 was also significant in predicting mortality. GBS was significant in predicting blood transfusion and need of intervention. PNED score was significant in all events except mortality. CONCLUSION: All four scores had lower predictive potential in predicting events in variceal bleed. However, AIMS65 & Rockall score were significant in predicting mortality, while GBS in predicting need of transfusion and intervention. PNED score was significant in all events except mortality.