A First Report of HCTZ and Dicyclomine Induced Uncharacteristic Contraction Alkalosis

Background Contraction alkalosis is characterized by low serum sodium and chloride and high serum carbon dioxide and bicarbonate levels. Case Report A 28-year-old Caucasian active-duty male with a history of autosomal dominant polycystic kidney disease and diarrhea-predominant Irritable Bowel Syndrome (D-IBS) presented to his primary care provider (PCP) with elevated blood pressure (136/96 mmHg), was diagnosed with stage-2 hypertension, and started oral HCTZ (25 mg/day). His medications included dicyclomine (10 mg oral three times daily). Subsequently, (Visit 1), his blood pressure was 130/91 mmHg and he was started on telmisartan (20 mg/day). At Visit 2, 4 weeks later, his blood pressure improved (121/73 mmHg); however, blood chemistry revealed elevated serum CO2 (32 mEq/L) and chloride (94 mmol/L). Four days later, the patient presented to the Emergency Department with dyspnea and swallowing difficulty. The patient returned to his PCP 3 days later complaining of cough, congestion, vomiting, and mild dyspnea, blood pressure of 124/84 mmHg. Two months later, sudden onset of projectile vomiting and abdominal pain while running was reported, resolved by rehydration and a single oral dose of prochlorperazine 25 mg. Three months later, (Visit 3), he complained of lightheadedness and cloudy judgment, suggesting contraction alkalosis. HCTZ was discontinued and telmisartan was increased to 20 mg twice daily. A follow-up blood chemistry panel 2 weeks later revealed serum chloride and CO2 levels within normal limits and blood pressure under 130/80 mmHg. Conclusion This is the first known report of contraction alkalosis driven by drug–drug interaction between dicyclomine and HCTZ.

Hyperchloremia is associated with poor renal outcome after coronary artery bypass grafting

Background Hyperchloremia is associated with the risks of several morbidities and mortality. However, its relationship with acute kidney injury (AKI) and end-stage renal disease (ESRD) in patients undergoing coronary artery bypass grafting (CABG) remains unresolved. Methods A total of 2977 patients undergoing CABG between 2003 and 2015 were retrospectively reviewed from two tertiary hospitals. Patients were categorized by serum chloride levels into normochloremia (95–105 mmol/L), mild hyperchloremia (106–110 mmol/L), and severe hyperchloremia (> 110 mmol/L). The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD were calculated after adjustment for multiple covariates. The death-adjusted risk of ESRD was additionally evaluated. Results Postoperative AKI occurred in 798 patients (26.5%). The hyperchloremia group had a higher risk of AKI than the normochloremia group, wherein the risk was incremental depending on the severity of hyperchloremia, as follows: ORs were 1.26 (1.06–1.51) and 1.95 (1.52–2.51) in the mild and severe hyperchloremia groups, respectively. During a median period of 7 years (maximum 15 years), 70 patients (2.3%) had ESRD. The severe hyperchloremia group was at an elevated risk of ESRD compared with the normochloremia group, with an HR of 2.43 (1.28–4.63). Even after adjusting for the competing risk of death, hyperchloremia was associated with the risk of ESRD. Conclusions Preoperative hyperchloremia is associated with poor renal outcomes such as AKI and ESRD after CABG. Accordingly, serum chloride should be monitored in patients undergoing CABG.

Elevated Serum Chloride Levels Contribute to a Poor Prognosis in Patients with IgA Nephropathy

Introduction. The identification of reliable prognostic factors is a crucial requirement for patients with IgA nephropathy (IgAN). Here, we explored the relationship between serum chloride levels and prognosis in patients with IgAN. Methods. We recruited all patients with primary IgAN, as diagnosed by renal biopsy, between 1st January 2015 and 1st April 2019. Patients were divided two groups (high chloride group and low chloride group) based on the best cut-off values from survival receiver operating characteristic (ROC) curves. The baseline clinicopathological characteristics of two groups were then compared. Cox proportional hazard models were used to determine the prognostic value of serum chloride levels in patients with IgAN. Finally, we screened reliable prognostic indicators and built a clinical prediction model and validated the performance of the model. Results. Compared with patients in the high chloride group, patients in the low chloride group had significantly lower levels of 24-hour urinary total protein (24 h-UTP), serum creatinine (sCr), and higher levels of hemoglobin (Hb), albumin (all p < 0.05 ), and less proportion of Oxford classification grade E1 (endothelial cell proliferation) and T2 (renal tubule atrophy or renal interstitial fibrosis). Cox analysis revealed that serum chloride level ≥ 105.4 mmol / L was a significant and independent risk factor for prognosis in patients with IgAN ( p < 0.05 ). Serum chloride, sCr, T, hypertension, and Hb were used to generate a predictive model for prognosis. The c -indices of our predictive model were 0.80, 0.86, and 0.78, for 1, 2, and 3 years, respectively; Brier scores were 0.06, 0.09, and 0.16, respectively. Conclusions. A serum chloride level ≥ 105.4 mmol / l was identified as a significant and independent risk factor for the prognosis of patients with IgAN. A predictive prognosis model was generated using serum chloride, sCr, T, hypertension, and Hb; this model exhibited a good predictive effect.

Low serum chloride level gives renin-angiotensin system inhibitor a prognostic impact in heart failure patients with preserved ejection fraction

Background Hypochloremia is associated with a poor prognosis of heart failure (HF) patients. This phenomenon is sustained even in HF with preserved ejection fraction (HFpEF). Serum chloride level is known to be affected by serum renin secretion; however, this relationship is one of the least investigated field in HF patients. Renin-angiotensin system (RAS) inhibitor is recommended as a first-line medication for HF patients with reduced left ventricular ejection fraction, but no prior studies of RAS inhibitors have achieved to improve the prognosis of HFpEF patients. Purpose We investigated the relationship between baseline serum chloride level and the prognostic impact of RAS inhibitor in HFpEF patients. Methods This is an observational study including 1,913 consecutive patients who admitted to hospital due to worsening of HF and discharged alive in a single university hospital. After excluding patients who received regular hemodialysis and whose left ventricular ejection fraction were under 50%, 506 HFpEF patients were ultimately analyzed. They were categorized into tertiles by serum chloride levels at discharge (T1: −100 mEq/L, T2: 101–104 mEq/L, T3: 105- mEq/L), and patients in each category were further divided into subgroups depending on the prescription of RAS inhibitor at discharge (RAS inhibitor group and Non-RAS inhibitor group). The primary endpoint of this study was death from any cause. Results During the observation period with 479 days of median follow-up, 77 (15.2%) died. Patients in the RAS inhibitor group had significantly better prognosis than those in the Non-RAS inhibitor group in T1 category (Log-rank: p=0.003, Figure). In contrast, there was no statistical difference in the mortality between the RAS inhibitor group and Non-RAS inhibitor group in T2 and T3 categories (Log-rank: p=0.15, p=0.81, respectively, Figure). Multivariate Cox regression analysis in T1 category revealed that taking RAS inhibitor at discharge was independently associated with a lower mortality rate, even after the adjustment of diverse covariates (hazard ratio: 0.40, 95% confidence interval: 0.20–0.80). Conclusion In this observational study, the administration of RAS inhibitor was associated with an improved prognosis of HFpEF patients only in low serum chloride level at discharge. Therapeutic strategy focusing on the chloride level may be one of the promising options to find the light on a unintervenable prognosis of HFpEF. FUNDunding Acknowledgement Type of funding sources: None.

Clinically Distinct Subtypes of Acute Kidney Injury on Hospital Admission Identified by Machine Learning Consensus Clustering

Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster’s key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality. Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients (p < 0.001). Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks.

Risk factors for recurrent positive results of the nucleic acid amplification test for COVID-19 patients: a retrospective study

Positive retests of COVID-19 represent a public health concern because of the increased risk of transmission. This study explored whether factors other than the nucleic acid amplification test (NAAT) contribute to positive retest results. Patients with COVID-19 admitted to the Guanggu district of the Hubei Maternal and Child Health Hospital between February 17 and March 28, 2020, were retrospectively included. The patients were grouped into the negative (n = 133) and positive (n = 51) retest groups. The results showed that the proportion of patients presenting with cough was higher (P < 0.001) and the proportion of patients with dyspnea was lower (P = 0.018) in the positive than in the negative retest group. The positive retest group showed shorter durations between symptom onset and hospitalization (P < 0.001) and symptom onset and the first positive NAAT (P = 0.033). The positive retest group had higher basophil counts (P = 0.023) and direct bilirubin (P = 0.032) and chlorine concentrations (P = 0.023) but lower potassium concentrations (P = 0.001) than the negative retest group. Multivariable regression analysis showed that coughing (OR = 7.59, 95% CI 2.28–25.32, P = 0.001) and serum chloride concentrations (OR = 1.38, 95% CI 1.08–1.77, P = 0.010) were independently associated with a positive retest result. Coughing and serum chloride concentrations were independent risk factors for positive NAAT retest results. Patients with a hospital stay of < 2 weeks or a short incubation period should stay in isolation and be monitored to reduce transmission. These results could help identify patients who require closer surveillance.