Incident dementia in kidney transplantation recipients: a matched comparative nationwide cohort study in South Korea.

BACKGROUND: Recent studies have shown that patients with end-stage renal disease (ESRD) are at elevated risk of dementia. However, whether kidney transplantation (KT) lowers the risk for incident dementia remains unclear. METHODS: From the Korean National Health Insurance Service database, we identified incident KT recipients aged ≥40 years without any history of dementia between 2007 and 2015. We also established a pair of age-, sex-, and inclusion year-matched control cohorts of patients with incident dialysis-dependent ESRD and members of the general population (GP) without a history of dementia, respectively. Cases of incident all-cause dementia, including Alzheimer disease (AD), vascular dementia (VD), and other kinds of dementia, were obtained from baseline until December 31, 2017. RESULTS: We followed 8,841 KT recipients, dialysis-dependent ESRD patients, and GP individuals for 48,371, 28,649, and 49,149 patient- years, respectively. Their mean age was 52.5 years, and 60.6% were male. Over the observation period, 55/43/19 KT recipients, 230/188/75 dialysis-dependent ESRD patients, and 38/32/14 GP individuals developed all-cause dementia/AD/VD. The risks of incident all-cause dementia, AD, and VD in KT recipients were similar to those in GP (hazard ratio: 0.74 [p = 0.20], 0.74 [p = 0.24], and 0.59 [p = 0.18], respectively) and significantly lower than those in dialysis-dependent ESRD patients (hazard ratio: 0.17 [p < 0.001], 0.16 [p < 0.001], and 0.16 [p < 0.001], respectively). Older age and diabetes mellitus at the time of KT were risk factors for incident all-cause dementia and AD in KT recipients. CONCLUSION: This is the first study to show a beneficial impact of KT on incident dementia compared to dialysis dependency.

Evidence-based hyponatremia management in liver disease.

Hyponatremia is primarily a water balance disorder associated with high morbidity and mortality. The pathophysiological mechanisms behind hyponatremia are multifactorial, and diagnosing and treating this disorder remains challenging. In this review, the classification, pathogenesis, and step-by-step management approaches for hyponatremia in patients with liver disease are described based on recent evidence. We summarize the five sequential steps of the traditional diagnostic approach: 1) confirm true hypotonic hyponatremia, 2) assess the severity of hyponatremia symptoms, 3) measure urine osmolality, 4) classify hyponatremia based on the urine sodium concentration and extracellular fluid status, and 5) rule out any coexisting endocrine disorder and renal failure. Distinct treatment strategies for hyponatremia in liver disease should be applied according to the symptoms, duration, and etiology of disease. Symptomatic hyponatremia requires immediate correction with 3% saline. Asymptomatic chronic hyponatremia in liver disease is prevalent and treatment plans should be individualized based on diagnosis. Treatment options for correcting hyponatremia in advanced liver disease may include water restriction; hypokalemia correction; and administration of vasopressin antagonists, albumin, and 3% saline. Safety concerns for patients with liver disease include a higher risk of osmotic demyelination syndrome.

Predicting outcomes of continuous renal replacement therapy using body composition monitoring: a deep-learning approach.

Fluid balance is a critical prognostic factor for patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated whether repeated fluid balance monitoring could improve prognosis in this clinical population. This was a multicenter retrospective study that included 784 patients (mean age, 67.8 years; males, 66.4%) with severe AKI requiring CRRT during 2017-2019 who were treated in eight tertiary hospitals in Korea. Sequential changes in total body water were compared between patients who died (event group) and those who survived (control group) using mixed-effects linear regression analyses. The performance of various machine learning methods, including recurrent neural networks, was compared to that of existing prognostic clinical scores. After adjusting for confounding factors, a marginal benefit of fluid balance was identified for the control group compared to that for the event group (p = 0.074). The deep-learning model using a recurrent neural network with an autoencoder and including fluid balance monitoring provided the best differentiation between the groups (area under the curve, 0.793) compared to 0.604 and 0.606 for SOFA and APACHE II scores, respectively. Our prognostic, deep-learning model underlines the importance of fluid balance monitoring for prognosis assessment among patients receiving CRRT.

Evaluation and management of hypernatremia in adults: clinical perspectives.

Hypernatremia is an occasionally encountered electrolyte disorder, which may lead to fatal consequences under improper management. Hypernatremia is a disorder of the homeostatic status regarding body water and sodium contents. This imbalance is the basis for the diagnostic approach to hypernatremia. We summarize the eight diagnostic steps of the traditional approach and introduce new biomarkers: exclude pseudohypernatremia, confirm glucose-corrected sodium concentrations, determine the extracellular volume status, measure urine sodium levels, measure urine volume and osmolality, check ongoing urinary electrolyte free water clearance, determine arginine vasopressin/copeptin levels, and assess other electrolyte disorders. Moreover, we suggest six steps to manage hypernatremia by replacing water deficits, ongoing water losses, and insensible water losses: identify underlying causes, distinguish between acute and chronic hypernatremia, determine the amount and rate of water administration, select the type of replacement solution, adjust the treatment schedule, and consider additional therapy for diabetes insipidus. Physicians may apply some of these steps to all patients with hypernatremia, and can also adapt the regimens for specific causes or situations.

De novo major cardiovascular events in kidney transplant recipients: a comparative matched cohort study.

BACKGROUND: Although cardiovascular disease is known to be one of the leading causes of death after kidney transplantation (KT), evidence on the risk difference of de novo major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs) compared with that in dialysis patients or the general population (GP) remains rare. METHODS: We identified KTRs using the nationwide health insurance database in South Korea and then 1:1 matched them with the dialysis and GP controls without a pre-existing MACE. The primary endpoint was defined as de novo MACEs consisting of myocardial infarction, coronary revascularization and ischemic stroke. The secondary endpoints were all-cause mortality and death-censored graft failure (DCGF) in KTRs. RESULTS: We included 4156 individuals in each of the three groups and followed them up for 4.7 years. De novo MACEs occurred in 3.7, 21.7 and 2.5 individuals per 1000 person-years in the KTRs, dialysis controls and GP controls, respectively. KTRs showed a lower MACE risk {adjusted hazard ratio (aHR) 0.16 [95% confidence interval (CI) 0.12-0.20], P < .001} than dialysis controls, whereas a similar MACE risk to GP controls [aHR 0.81 (95% CI 0.52-1.27), P = .365]. In addition, KTRs showed a similar MACE risk compared with the GP group, regardless of age, sex and the presence of comorbidities, including hypertension, diabetes and dyslipidemia. Among KTRs, de novo MACEs were associated with an increased risk of all-cause mortality, but not with DCGF. CONCLUSIONS: De novo MACEs in KTRs were much lower than that in dialysis patients and had a similar risk to the GP, but once it occurred it caused elevated mortality risk in KTRs.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Incidence of depression in kidney transplant recipients in South Korea: a long-term population-based study.

Depression is associated with impaired quality of life and increased morbidity and mortality in end-stage kidney disease (ESKD) patients and kidney transplantation (KT) recipients. Depression incidence after KT is unclear. We compared depression incidence among KT recipients, ESKD patients, and healthy controls (HCs). We analyzed a nationwide health insurance database in South Korea and identified patients who underwent KT during 2007-2015. Participants were matched for age, sex, and inclusion year. KT and ESKD patients were further matched for hypertension and diabetes mellitus history. The incidence rate (IR, per 1000 patients-years) of depression was compared among KT, ESKD, and HC groups. We analyzed 5,234 patients per group. Depression incidence was markedly lower in KT than ESKD patients (IR, 18.87 vs. 58.03; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.30‒0.36), but only slightly higher in KT recipients than in HCs (IR, 18.87 vs. 17.49; HR, 1.08; 95% CI, 0.96‒1.22). After adjusting for comorbidities, the depression risk was lower in KT recipients than in HCs (adjusted HR, 0.52; 95% CI, 0.44‒0.62; p < 0.001), whereas it remained higher in ESKD patients than in HCs (adjusted HR, 1.60; 95% CI, 1.36‒1.87; p < 0.001). Among KT recipients, older age, female sex, lower economic status, and more comorbidities were associated with increased depression risk. Incident depression after KT increased mortality, graft failure, and death-censored graft failure risks in KT recipients. Our data suggest a broader role of KT than previously appreciated in terms of improving quality of life by reducing depression risk.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Efficacy and safety of rapid intermittent bolus compared with slow continuous infusion in patients with severe hypernatremia (SALSA II trial): a study protocol for a randomized controlled trial.

BACKGROUND: Hypernatremia is a common electrolyte disorder in children and elderly people and has high short-term mortality. However, no high-quality studies have examined the correction rate of hypernatremia and the amount of fluid required for correction. Therefore, in this study, we will compare the efficacy and safety of rapid intermittent bolus (RIB) and slow continuous infusion (SCI) of electrolyte-free solution in hypernatremia treatment. METHODS: This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental groups. A total of 166 participants with severe hypernatremia will be enrolled and divided into two randomized groups; both the RIB and SCI groups will be managed with electrolyte-free water. We plan to infuse the same amount of fluid to both groups, for 1 hour in the RIB group and continuously in the SCI group. The primary outcome is a rapid decrease in serum sodium levels within 24 hours. The secondary outcomes will further compare the efficacy and safety of the two treatment protocols. CONCLUSION: This is the first randomized controlled trial to evaluate the efficacy and safety of RIB correction compared with SCI in adult patients with severe hypernatremia.

Risk factors for overcorrection of severe hyponatremia: a post hoc analysis of the SALSA trial.

BACKGROUND: Hyponatremia overcorrection can result in irreversible neurologic impairment such as osmotic demyelination syndrome. Few prospective studies have identified patients undergoing hypertonic saline treatment with a high risk of hyponatremia overcorrection. METHODS: We conducted a post hoc analysis of a multicenter, prospective randomized controlled study, the SALSA trial, in 178 patients aged above 18 years with symptomatic hyponatremia (mean age, 73.1 years; mean serum sodium level, 118.2 mEq/L). Overcorrection was defined as an increase in serum sodium levels by >12 or 18 mEq/L within 24 or 48 hours, respectively. RESULTS: Among the 178 patients, 37 experienced hyponatremia overcorrection (20.8%), which was independently associated with initial serum sodium level (≤110, 110-115, 115-120, and 120-125 mEq/L with 7, 4, 2, and 0 points, respectively), chronic alcoholism (7 points), severe symptoms of hyponatremia (3 points), and initial potassium level (<3.0 mEq/L, 3 points). The NASK (hypoNatremia, Alcoholism, Severe symptoms, and hypoKalemia) score was derived from four risk factors for hyponatremia overcorrection and was significantly associated with overcorrection (odds ratio, 1.41; 95% confidence interval, 1.24-1.61; p < 0.01) with good discrimination (area under the receiver-operating characteristic [AUROC] curve, 0.76; 95% CI, 0.66-0.85; p < 0.01). The AUROC curve of the NASK score was statistically better compared with those of each risk factor. CONCLUSION: In treating patients with symptomatic hyponatremia, individuals with high hyponatremia overcorrection risks were predictable using a novel risk score summarizing baseline information.

Changes in duplex ultrasound parameters during maturation according to arteriovenous access types in incident hemodialysis patients.

BACKGROUND: Little is known about the changes in hemodynamic parameters during arteriovenous (AV) access maturation using duplex ultrasound according to radiocephalic fistula (RCF), brachiocephalic fistula (BCF), and AV graft (AVG) in incident hemodialysis (HD) patient. The objective of this study was to evaluate changes and differences in brachial artery flow rate (BAFR) and related parameters affecting maturation by duplex ultrasound in incident HD patients according to access type. METHODS: This study was an observational study conducted from March 2019 to October 2020. During the study period, 109 incident patients underwent new AV access creation, of which 100 were included in the study. The duplex ultrasound was performed on the day prior to access creation, further, day 1, 2 weeks, and 4 weeks later after access creation in incident HD patients. RESULTS: Among all the patients, 38 (38%) received BCF, while 26 (26%) underwent RCF. Of the patients with AVG, 18 (50%) had a forearm loop AVG. The overall mean age was 62.2 ± 13.8 years (range, 32-89). The BAFR increased about 6.9 times in the RCF, 17.4 times in the BCF, and 19.5 times in the AVG at day 1. The median BAFR measured on day 1 was 580.4 mL/min for RC, 1029.0 mL/min for BC, and 1133.0 mL/min for AVG. Relative to the values measured in week 4, the BAFR on day 1 was 69.5% in RCF, 90.6% in BCF, and 93.9% in AVG. The acceleration decreased most significantly on day 1(p < 0.05). The acceleration time increased significantly on day 1 (p < 0.05) and beyond during maturation in the RCF and BCF. The BAFR of the RCF had a significantly negative correlation with the pulsatility index. The BAFR of the BCF showed a significantly positive correlation with the systolic and diastolic blood pressure but negatively correlated with pulse rate. The BAFR of the AVG showed a significant positive correlation with the diameter of the outflow vein. CONCLUSIONS: There were differences in the clinical and duplex parameters during maturation according to access type. The most dramatic changes of duplex parameters were on the day after AV access creation regardless of AV access types. Though RCF had a lower BAFR rate compared to BCF and AVG, it already had a sufficient BAFR required for adequate HD treatment the day after creation. The BAFR of BCF was not different from that of AVG.

GDF-15 Predicts In-Hospital Mortality of Critically Ill Patients with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy: A Multicenter Prospective Study.

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 patients whose blood sample was available were analyzed. Patients were divided into three groups according to the GDF-15 concentrations. The median GDF-15 level was 7865.5 pg/mL (496.9 pg/mL in the healthy control patients). Baseline characteristics were not different among tertile groups except the severity scores and serum lactate level, which were higher in the third tertile. After adjusting for confounding factors, the patients with higher GDF-15 had significantly increased risk of mortality (second tertile: adjusted hazards ratio [aHR], 3.67; 95% confidence interval [CI], 1.05-12.76; p = 0.041; third tertile: aHR, 6.81; 95% CI, 1.98-23.44; p = 0.002). Furthermore, GDF-15 predicted in-hospital mortality (area under the curve, 0.710; 95% CI, 0.585-0.815) better than APACHE II and SOFA scores. Serum GDF-15 concentration was elevated in AKI patients requiring CRRT, higher in more severe patients. GDF-15 is a better independent predictor for in-hospital mortality of critically ill AKI patients than the traditional risk scoring system such as APACHE II and SOFA scores.

Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2Vaccination in Patient with Multiple Myeloma.

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.

Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study.

BACKGROUND: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. METHODS: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed. RESULTS: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). CONCLUSION: There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Incident Parkinson's disease in kidney transplantation recipients: a nationwide population-based cohort study in Korea.

This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson' disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson's disease between 2007 and 2015. We established two control cohorts without a history of Parkinson' disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson's disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson' disease. Risk of incident Parkinson's disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson's disease in KT recipients.

Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial.

Importance: Few high-quality studies have clarified whether hypertonic saline is best administered as slow continuous infusion (SCI) therapy or rapid intermittent bolus (RIB) therapy for symptomatic severe hyponatremia. Objective: To compare the risk of overcorrection in RIB and SCI with hypertonic saline in patients with symptomatic hyponatremia. Design, Setting, and Participants: This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial enrolled 178 patients older than 18 years with moderately severe to severe hyponatremia and glucose-corrected serum sodium (sNa) levels of 125 mmol/L or less. Recruitment took place from August 24, 2016, until August 21, 2019, across emergency departments and wards of 3 general hospitals in the Republic of Korea. Interventions: Either RIB or SCI of hypertonic saline, 3%, for 24 to 48 hours stratified by the severity of clinical symptoms. Main Outcome and Measures: The primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Secondary and post hoc outcomes included efficacy and safety of the treatment approaches. The sNa concentrations were measured every 6 hours for 2 days. Results: The 178 patients (mean [SD] age, 73.1 [12.2] years; 80 (44.9%) male; mean [SD] sNa concentrations, 118.2 [5.0] mmol/L) were randomly assigned to the RIB group (n = 87) or the SCI group (n = 91). Overcorrection occurred in 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, -6.9% [95% CI, -18.8% to 4.9%]; P = .26). The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, -15.8% [95% CI, -30.3% to -1.3%]; P = .04; number needed to treat, 6.3). Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms, but RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour (intention-to-treat analysis: 28 of 87 (32.2%) vs 16 of 91 (17.6%) patients, respectively; absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; number needed to treat, 6.8; per-protocol analysis: 21 of 72 (29.2%) vs 12 of 73 (16.4%) patients, respectively; absolute risk difference, 12.7% [95% CI, -0.8% to 26.2%]; P = .07). The statistical significance of the intention-to-treat and per-protocol analyses were similar for all outcomes except for achieving the target correction rate within 1 hour. Conclusions and Relevance: This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the current consensus guidelines. Trial Registration: ClinicalTrials.org Identifier: NCT02887469.