Jefferson L. Triozzi, MD, MSCI; Zhihong Yu, MS, PhD; Ayush Giri, MS, PhD; Hua-Chang Chen, PhD; Otis D. Wilson, BBA; Brian Ferolito, MS; T. Alp Ikizler, MD; Elvis A. Akwo, MD, MS; Cassianne Robinson-Cohen, PhD; John Michael Gaziano, MD, MPH; Kelly Cho, PhD, MPH; Lawrence S. Phillips, MD; Ran Tao, PhD; Alexandre C. Pereira, MD, PhD; Adriana M. Hung, MD, MPH; for the VA Million Veteran Program
Key Points
Question Are glucagon-like peptide 1 receptor agonists (GLP-1RAs) associated with kidney disease progression?
Findings In this genetic association study of 353 153 adults, higher genetic GLP1R gene expression as a proxy for GLP-1RAs was associated with a small reduction in the risk of kidney disease progression, even after adjusting for obesity and diabetes.
Meaning These findings support a nephroprotective role of GLP-1RAs.
Abstract
IMPORTANCE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control.
OBJECTIVE To investigate the association of genetically proxied GLP-1RAs with kidney disease
DESIGN, SETTING, AND PARTICIPANTS This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024.
EXPOSURES Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project.
MAIN OUTCOMES AND MEASURES The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression.
RESULTS Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status.
CONCLUSIONS AND RELEVANCE In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.
Daniela Milosheska . Robert Roskar
Received: August 17, 2022 / Accepted: September 6, 2022 / Published online: October 11, 2022
©The Author(s) 2022
ABSTRACT
Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation. Other retinoids present in topical medicines are used for various indications, but only tazarotene is also approved as adjunctive agent for treatment of facial fine wrinkling and pigmentation. The most commonly used retinoids such as retinol, retinaldehyde, and retinyl palmitate are contained in cosmeceuticals regulated as cosmetics. Since clinical efficacy studies are not required for marketing cosmetic formulations, there are concerns about the efficacy of these retinoids.
From a formulation perspective, retinoids pose a challenge to researchers as a result of their proven instability, low penetration, and potential for skin irritation. Therefore, novel delivery systems based on nanotechnology are being developed to overcome the limitations of conventional formulations and improve user compliance. In this review, the clinical evidence for retinoids in conventional and nanoformulations for topical antiaging treatments was evaluated. In addition, an overview of the comparison clinical trials between tretinoin and other retinoids is presented. In general, there is a lack of evidence from properly designed clinical trials to support the claimed efficacy of the most commonly used retinoids as antiaging agents in cosmeceuticals. Of the other retinoids contained in medicines, tazarotene and adapalene have clinically evaluated antiaging effects compared to tretinoin and may be considered as potential alternatives for antiaging treatments. The promising potential of retinoid nanoformulations requires a more comprehensive evaluation with additional studies to support the preliminary findings.
Keywords: Antiaging; Clinical evidence; Cosmeceuticals; Nanoformulations; Retinoids; Retinol; Tretinoin
Key Summary Points
Tretinoin is the retinoid present in medicines for topical application with the strongest clinical evidence of antiaging Tazarotene and adapalene may be considered as tretinoin alternatives for antiaging treatments.
Clinical evidence is lacking for retinoids contained in cosmeceuticals for topical antiaging treatments.
Novel formulations based on nanotechnology are being developed to overcome the major drawbacks of retinoid Further evaluation with in vivo testing and clinical trials are needed to support the preclinical results for the developed nanoformulations containing retinoids.
D. Milosheska INSLAB, Maribor, Slovenia
R. Roskar (&)
University of Ljubljana, Faculty of Pharmacy, Askerceva cesta 7, 1000 Ljubljana, Slovenia
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在所有下肢溃疡中，静脉曲张性的溃疡占70%以上，静脉曲张性溃疡即下肢静脉曲张引起溃疡。
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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