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Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week.
Kittipibul, V, Cox, ZL, Chesdachai, S, Fiuzat, M, Lindenfeld, J, Mentz, RJ
Journal of the American College of Cardiology. 2024;(16):1568-1578
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.
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Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.
Tangpricha, V, Lukemire, J, Chen, Y, Binongo, JNG, Judd, SE, Michalski, ES, Lee, MJ, Walker, S, Ziegler, TR, Tirouvanziam, R, et al
The American journal of clinical nutrition. 2019;109(3):544-553
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Patients with cystic fibrosis (CF) have a mutation in a particular gene which results in derangements in chloride transport across epithelial surfaces, leading to abnormally thickened mucus on the surfaces of the lung, pancreas, intestines, and other organs. The aim of this study was to investigate the impact of high-dose vitamin D3 administered to adults with CF during and after an acute pulmonary exacerbation. The study is a double-blind, randomised, placebo-controlled clinical trial. Subjects were randomly assigned and stratified to one of the two groups: vitamin D (5 capsules of vitamin D3 containing 50,000 IU) or placebo (5 capsules that were identical in size, shape, and colour to the vitamin D3 capsule). Results demonstrated that high-dose vitamin D3 administration to adults with CF initiated at the time of a pulmonary exacerbation did not improve time to next pulmonary exacerbation or 1 year survival. Authors conclude that a high-dose vitamin D3 bolus, combined with maintenance therapy given to adults with CF during acute pulmonary exacerbation of CF did not improve 1 year survival or recovery of lung function.
Abstract
BACKGROUND Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. OBJECTIVES The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. METHODS This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). RESULTS A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. CONCLUSIONS Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.
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Prospective, Randomized, Double-Blind, Parallel-Group, Comparative Effectiveness Clinical Trial Comparing a Powder Vehicle Compound of Vitamin D With an Oil Vehicle Compound in Adults With Cystic Fibrosis.
Hermes, WA, Alvarez, JA, Lee, MJ, Chesdachai, S, Lodin, D, Horst, R, Tangpricha, V
JPEN. Journal of parenteral and enteral nutrition. 2017;(6):952-958
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Abstract
BACKGROUND There is little consensus on the most efficacious vehicle substance for vitamin D supplements. Fat malabsorption may impede the ability of patients with cystic fibrosis (CF) to absorb vitamin D in an oil vehicle. We hypothesized that vitamin D contained in a powder vehicle would be absorbed more efficiently than vitamin D contained in an oil vehicle in patients with CF. METHODS In this double-blind, randomized controlled trial, hospitalized adults with CF were given a one-time bolus dose of 100,000 IU of cholecalciferol (D3) in a powder-based or oil-based vehicle. Serum D3, 25-hydroxyvitamin D, and parathyroid hormone concentrations were analyzed at 0, 12, 24, and 48 hours posttreatment. The area under the curve for serum D3 and the 12-hour time point were also assessed as indicators of D3 absorption. RESULTS This trial was completed by 15 patients with CF. The median (interquartile range) age, body mass index, and forced expiratory volume in 1 second were 23.7 (19.9-33.2) years, 19.9 (18.6-22.6) kg/m2, and 63% (37%-80%), respectively. The increase in serum D3 and the area under the curve was greater in the powder group ( P = .002 and P = .036, respectively). Serum D3 was higher at 12 hours in the powder group compared with the oil group ( P = .002), although levels were similar between groups by 48 hours. CONCLUSIONS In adults with CF, cholecalciferol is more efficiently absorbed in a powder compared with an oil vehicle. Physicians should consider prescribing vitamin D in a powder vehicle in patients with CF to improve the absorption of vitamin D from supplements.
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The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis.
Tangpricha, V, Smith, EM, Binongo, J, Judd, SE, Ziegler, TR, Walker, S, Tirouvanziam, R, Zughaier, SM, Lee, MJ, Chesdachai, S, et al
Contemporary clinical trials communications. 2017;:39-45
Abstract
Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF). Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a multi-center, double-blind, randomized, placebo-controlled trial that will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 hours of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 second (FEV1), blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.
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Treatment of vitamin D deficiency in cystic fibrosis.
Chesdachai, S, Tangpricha, V
The Journal of steroid biochemistry and molecular biology. 2016;:36-39
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Abstract
Vitamin D deficiency occurs frequently in patients with cystic fibrosis (CF). Vitamin D is important for optimal mineralization of bone and may be important for other comorbidities commonly occurring in patients with CF. Vitamin D deficiency in patients with CF can arise from various causes including pancreatic exocrine insufficiency, lack of outdoor activity, and alterations of vitamin D metabolism. Due to fat malabsorption stemming from pancreatic insufficiency, higher oral doses of vitamin D are necessary to correct and maintain optimal vitamin D status in patients with CF. Recent studies have demonstrated that higher vitamin D status is associated with better lung function and that vitamin D therapy may help recovery from pulmonary exacerbations of CF. The mechanisms by which vitamin D may exert its beneficial actions in CF are unclear but likely related to the role vitamin D has in modulating the adaptive and innate immune response. Large randomized clinical studies to evaluate the potential role of vitamin D as adjunctive therapy in CF that goes beyond bone are necessary.