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Item Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease(Massachusetts Medical Society, 2021) Agarwal, Rajiv; Sinha, Arjun D.; Cramer, Andrew E.; Balmes-Fenwick, Mary; Dickinson, Jazmyn H.; Ouyang, Fangqian; Tu, Wanzhu; Medicine, School of MedicineBackground: Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease. Methods: We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed. Results: A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m2 of body-surface area and the mean number of antihypertensive medications prescribed was 3.4±1.4. At randomization, the mean 24-hour ambulatory systolic blood pressure was 142.6±8.1 mm Hg in the chlorthalidone group and 140.1±8.1 mm Hg in the placebo group and the mean 24-hour ambulatory diastolic blood pressure was 74.6±10.1 mm Hg and 72.8±9.3 mm Hg, respectively. The adjusted change in 24-hour systolic blood pressure from baseline to 12 weeks was -11.0 mm Hg (95% confidence interval [CI], -13.9 to -8.1) in the chlorthalidone group and -0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. The between-group difference was -10.5 mm Hg (95% CI, -14.6 to -6.4) (P<0.001). The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group. Conclusions: Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo.Item Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial(Elsevier, 2021) Sarraju, Ashish; Li, JingWei; Cannon, Christopher P.; Chang, Tara I.; Agarwal, Rajiv; Bakris, George; Charytan, David M.; de Zeeuw, Dick; Greene, Tom; Heerspink, Hiddo J. L.; Levin, Adeera; Neal, Bruce; Pollock, Carol; Wheeler, David C.; Yavin, Yshai; Zhang, Hong; Zinman, Bernard; Perkovic, Vlado; Jardine, Meg; Mahaffey, Kenneth W.; Medicine, School of MedicineWe aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.Item Improving Postdischarge Outcomes in Acute Heart Failure(Wolters Kluwer, 2018-07) Chioncel, Ovidiu; Collins, Sean P.; Ambrosy, Andrew P.; Pang, Peter S.; Antohi, Elena-Laura; Iliescu, Vlad Anton; Maggioni, Aldo P.; Butler, Javed; Mebazaa, Alexandre; Emergency Medicine, IU School of MedicineThe global burden that acute heart failure (AHF) carries has remained unchanged over the past several decades (1). European registries (2–5) showed that 1-year outcome rates remain unacceptably high (Table 1) and confirm that hospitalization for AHF represents a change in the natural history of the disease process(6). As patients hospitalized for HF have a bad prognosis, it is crucial to utilize hospitalization as an opportunity to: 1) assess the individual components of the cardiac substrate; 2) identify and treat comorbidities; 3) identify early, safe endpoints of therapy to facilitate timely hospital discharge and outpatient follow-up; and 4) implement and begin optimization guideline-directed medical therapies (GDMTs). As outcomes are influenced by many factors, many of which are incompletely understood, a systematic approach is proposed that should start with admission and continues through post-discharge (7).Item Mapping the Nephron Exercise Incorporates Multiple Learning Strategies(Association of American Medical Colleges, 2017-09-28) Hopper, Mari K.; Anderson, Maria A.; Lipp, Sarah N.; Cellular and Integrative Physiology, School of MedicineIntroduction: Understanding the location and action of nephron transporters and channels is important to the understanding of renal function. As each region of the nephron is unique in its inclusion of specific transporters and channels, mapping of the nephron is an effective first step in understanding overall nephron processing. We describe a small-group, active-learning exercise that facilitates students' ability to understand renal processing within each region of the nephron. Methods: Following an overview lecture on renal transporters and channels, small groups of students worked cooperatively to map the nephron. This 2-hour, collaborative exercise was developed to reinforce key concepts in renal processing of ions and nutrients and, at the same time, utilize effective learning strategies. Learning strategies incorporated in this exercise include small-group collaboration, peer teaching, retrieval practice using an audience response system, and elaboration through discussion. Results: Written examination was used to assess student understanding. Students demonstrated higher performance on a subset of questions related to this learning activity compared to the overall exam. Highly positive feedback was provided by a convenience sample of students completing an anonymous survey. Discussion: This nephron-mapping exercise was an effective means to promote synthesis and analysis of lecture content and engage students in methods that enhance learning.Item Should we CLICK on chlorthalidone for treatment-resistant hypertension in chronic kidney disease?(Oxford University Press, 2022-12-20) Agarwal, Rajiv; Medicine, School of MedicineTreatment-resistant hypertension is common among patients with advanced chronic kidney disease (CKD). In people with preserved kidney function, spironolactone is an evidence-based treatment. However, the risk for hyperkalemia limits its use in people with more advanced CKD. In the Chlorthalidone in Chronic Kidney Disease (CLICK) trial, 160 patients with stage 4 CKD and poorly controlled hypertension as confirmed by 24-hour ambulatory blood pressure (ABP) monitoring were randomly assigned to either placebo or chlorthalidone 12.5 mg daily in a 1:1 ratio stratified by prior loop diuretic use. The primary endpoint was the change in 24-hour systolic ABP from baseline to 12 weeks. The trial showed a treatment-induced reduction of 24-hour systolic ABP by 10.5 mmHg. Of the 160 patients randomized, 113 (71%) had resistant hypertension, of which 90 (80%) were on loop diuretics and the mean number of antihypertensive medications prescribed was 4.1 (standard deviation 1.1). In this subgroup of patients with treatment-resistant hypertension, the adjusted change from baseline to 12 weeks in the between-group difference in 24-hour systolic ABP was -13.9 mmHg (95% CI -19.4 to -8.4; P < .0001). Furthermore, compared with placebo, the urine albumin:creatinine ratio in the chlorthalidone group at 12 weeks was 54% lower (95% CI -65 to -40). Following randomization, hypokalemia, reversible increases in serum creatinine, hyperglycemia, dizziness, orthostatic hypotension and hyperuricemia occurred more frequently in the chlorthalidone group. Chlorthalidone has the potential to improve BP control among patients with advanced CKD and treatment-resistant hypertension. However, caution is advised when treating patients, especially when they are on loop diuretics.