Kashani, Kianoush

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

Abstract Introduction: Kidneys play a primary role in electrolyte homeostasis. The association between serum sodium level and mortality or the need for kidney replacement therapy during acute kidney injury has not been adequately explored. Methods: In this prospective cohort study, we enrolled patients admitted to the Civil Hospital of Guadalajara from August 2017 to March 2020. We divided patients into five groups based on the serum sodium level trajectories up to ten days following hospitalization, 1) stable normonatremia (serum sodium 135 and 145 mEq/L), 2) fluctuating serum sodium levels (increased/decreased in and out of normonatremia), 3) uncorrected hyponatremia, 4) corrected hyponatremia, and 5) uncorrected hypernatremia. We assessed the association of serum sodium trajectories with mortality and the need for kidney replacement therapy (secondary objective). Results: A total of 288 patients were included. The mean age was 55±18 years, and 175 (60.7%) were male. Acute kidney injury stage 3 was present in 145 (51%). Kidney replacement therapy started in 72 (25%) patients, and 45 (15.6%) died. After adjusting for confounders, 10-day hospital mortality was significantly higher in group 5 (HR, 3.12; 95% CI, 1.05 to 9.24, p = 0.03), and kidney replacement therapy initiation was higher in group 3 (HR, 2.44; 95% CI, 1.04 to 5.70, p = 0.03) compared with group 1. Conclusion: In our prospective cohort, most patients with acute kidney injury had alterations in serum sodium. Uncorrected hypernatremia was associated with death, and uncorrected hyponatremia was correlated with the need for kidney replacement therapy.

AbstractHigh‐dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single‐center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7‐hydroxy‐MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine‐ or cystatin C‐based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2–75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8–11.3) grams. Median clearance was similar across three dosing levels at 4.5–5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4‐h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C‐based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Introduction: Renal dysfunction, as defined by elevated serum creatinine, is associated with decreased survival among patients resuscitated after out-of-hospital cardiac arrest (OHCA). Less is known about other measures of renal function and outcomes after OHCA. Hypothesis: BUN and urine output will predict mortality after OHCA. Methods: Retrospective single-center cohort study of 276 adult OHCA patients treated with targeted temperature management after OHCA between December 2005 and September 2016. Fluid balance and urine output were recorded for the first 6, 12 and 24 hours. Initial laboratory values were determined from electronic records. Hospital survivors and non-survivors were compared using the Wilcoxon test, and multivariate analysis was performed to determine predictors of hospital death. Results: Mean age was 63±12 years, and 204 (73%) were male; shockable rhythm occurred in 241 (87%). Inpatient death occurred in 111 (40%). Hospital survivors had lower initial BUN (13 vs. 20 mg/dL) and creatinine (1.1 vs. 1.5 mg/dL); all p <.001. Hospital survivors had higher (p <.001) urine output during the first 6 hours (1,091 vs. 559 ml), 12 hours (1,583 vs. 843 ml), and 24 hours (2,215 vs. 1,294 ml). Higher initial BUN (OR 1.12, 95% CI 1.07-1.18) and creatinine (OR 3.036, 95% CI 1.65-5.59) predicted hospital mortality; all p <.001. Urine output during the first 24 hours was associated with hospital mortality (OR 0.57 per each 1 L, 95% CI 0.45-0.72, p <.001; AUROC 0.73, optimal cut-off 1 L). Patients with 24-hour urine output <1 L were at increased risk of hospital death (66.3% vs. 26.0%, unadjusted OR 5.61, 95% CI 3.27-9.63, p <.001). Initial BUN (adjusted OR 1.09, 95% CI 1.01-1.16, p=.02) and urine output during the first 24 hours (adjusted OR 0.71 per each 1 L; 95% CI 0.52-0.97, p=.03) remained predictive of hospital mortality after adjustment for patient characteristics and illness severity. Conclusions: Lower 24-hour urine output and higher initial BUN were associated with higher hospital mortality among patients resuscitated from OHCA, even after adjustment for illness severity. Serum creatinine was not a significant predictor of mortality. This emphasizes the importance of low urine output as a prognostic marker and therapeutic target after OHCA.

OBJECTIVES: To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION: Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION: Data were collected on all-cause mortality, hospital length of stay, heart failure–related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS: Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46–0.67; p < 0.05; I2 = 12%) and heart failure–related readmissions (relative risk, 0.50; 95% CI, 0.33–0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, –3.28 d; 95% CI, –4.14 to –2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92–662.81; p < 0.05; I2 = 76%), weight loss (mean difference, –1.76 kg; 95% CI, –2.52 to –1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98–8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47–70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, –0.46 mg/dL; 95% CI, –0.51 to –0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS: Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.

Introduction: Lactate is a known prognostic marker in critically ill patients, including patients with shock and cardiac arrest (CA). We sought to describe the association between admission lactate and hospital mortality in cardiac intensive care unit (CICU) patients, particularly those with CA. Methods: We retrospectively evaluated adult patients admitted to a tertiary care CICU from January 1, 2007, to April 30, 2018, with measured lactate on admission. We examined hospital mortality as a function of admission lactate level in patients with and without CA. Multivariable logistic regression was used to determine predictors of hospital mortality in the overall cohort, after adjustment for clinical characteristics, therapies, and illness severity. Results: We included 3,042 patients with a median age of 70 years (IQR 60-80), including 40.5% (n=1,233) females. There were 789 patients (26.1%) with a diagnosis of CA. The median APACHE-4 predicted mortality was 24.2% (IQR 10.9-50.7), and 50.8% (n=1546) were treated with vasoactive infusions. The median lactate on admission was 1.8 mmol/L (IQR 1.1-3.0). CICU mortality occurred in 478 (15.7%) patients) and hospital mortality occurred in 706 (23.2%) patients. Hospital mortality rose progressively as a function of admission lactate ( Figure ). On univariable analysis, lactate was associated with increased hospital mortality among the overall cohort (OR 1.36, CI 1.31-1.42, P < .001; AUROC 0.71), patients with CA (OR 1.33 (95% CI 1.25-1.41, P < .01; AUROC 0.73), and patients without CA (OR 1.27, CI 1.21-1.34, P < .01; AUROC 0.64). On multivariable analysis, lactate was one of the most significant predictors of hospital mortality (adjusted OR 1.13 per mmol/L, 95% CI 1.08-1.18, P < .001). Conclusions: Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, especially those with CA. The prognostic value of lactate levels may help inform clinicians caring for CICU patients.