scholarly journals Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Volker Vallon ◽  
Subodh Verma
Keyword(s):  
Ketone Bodies ◽  
Heart Function ◽  
Oxygen Demand ◽  
Sglt2 Inhibitors ◽  
Annual Review ◽  
Publication Date ◽  
Protective Mechanisms ◽  
Filtration Barrier ◽  
Urinary Glucose ◽  
Resistance To Diuretics

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Brain-Protective Mechanisms of Transcription Factor NRF2: Toward a Common Strategy for Neurodegenerative Diseases

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Antonio Cuadrado
Keyword(s):  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Cell ◽  
Current Status ◽  
Annual Review ◽  
Publication Date ◽  
Related Factor ◽  
Protective Mechanisms ◽  
Cell Functions ◽  
Pass Through

Neurodegenerative diseases are characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflammation, and proteostasis. The transcription factor nuclear factor erythroid 2–related factor 2 (NRF2) is a master controller of these functions, and its overall activity is compromised during aging and in these diseases. However, NRF2 can be activated pharmacologically and is now being considered a common therapeutic target. Many gaps still exist in our knowledge of the specific role that NRF2 plays in specialized brain cell functions or how these cells respond to the hallmarks of these diseases. This review discusses the relevance of NRF2 to several hallmark features of neurodegenerative diseases and the current status of pharmacological activators that might pass through the blood-brain barrier and provide a disease-modifying effect. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Kevin S. Shah ◽  
James C. Fang
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Blood Glucose Control ◽  
Sglt2 Inhibitors ◽  
Annual Review ◽  
Diabetic Patients ◽  
Publication Date ◽  
Cardiovascular Outcome Trials ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve blood glucose control by blocking renal glucose reabsorption with little subsequent risk of hypoglycemia. Consequently, there are decreases in plasma volume, body weight, and blood pressure. Additional putative benefits include improved cardiovascular energetics, decreased systemic inflammation, and less renal dysfunction. Multiple cardiovascular outcome trials in diabetic patients have demonstrated this drug class reduces the risk of adverse cardiovascular events. Reductions in heart failure (HF) hospitalization suggested that SGLT2 inhibitors might prove useful for the primary treatment of HF. Two large subsequent trials studying SGLT2 inhibitors in heart failure with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular mortality, HF hospitalizations, and renal-specific adverse events. This medication class is now recognized as a new pillar of therapy for patients with HFrEF. The cardiovascular and HF community await the results of ongoing trials of SGLT2 inhibition in patients with HF with preserved ejection fraction. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude
Keyword(s):  
Immune Modulation ◽  
Viral Infections ◽  
Viral Evolution ◽  
Endogenous Retroviruses ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Self Tolerance ◽  
Vertebrate Hosts ◽  
Insight Into

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity

2017 ◽  
Vol 313 (4) ◽  
pp. F951-F954 ◽  
Author(s):  
Danielle L. Saly ◽  
Mark A. Perazella
Keyword(s):  
Early Stage ◽  
Functional Decline ◽  
Healthcare Providers ◽  
Sglt2 Inhibitor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Chip Technology ◽  
Urinary Glucose

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) has collected over 100 cases of acute kidney injury (AKI) for canagloflozin and dapagliflozin since their approval. Of the 101 patients, 96 required hospitalization, 22 required intensive care unit admission, and 15 underwent hemodialysis. The FDA now requires that AKI be listed as a potential side effect of the SGLT2 inhibitors along with cautious prescription of these drugs with other medications, such as renin-angiotensin-system antagonists, diuretics, and NSAIDs. It is unclear, however, whether this FAERS reported “AKI” actually represents structural kidney injury, as randomized, controlled trials of these drugs do not describe AKI as an adverse event despite coprescription with RAS blockers and diuretics. As a result of this FDA warning, diabetic patients with early-stage CKD may not be prescribed an SGLT2 inhibitor for fear of AKI. Thus, it is imperative to ascertain whether the reported AKI represents true structural kidney injury or a functional decline in glomerular filtration rate. We propose using readily available clinical tools with experimental biomarkers of kidney injury and kidney-on-a-chip technology to resolve this question and provide solid evidence about the AKI risk of these drugs for healthcare providers.

Advancing Socioeconomic Rights Through Interdisciplinary Factfinding: Opportunities and Challenges

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sarah Knuckey ◽  
Joshua D. Fisher ◽  
Amanda M. Klasing ◽  
Tess Russo ◽  
Margaret L. Satterthwaite
Keyword(s):  
Human Rights ◽  
Mixed Methods ◽  
Social Science ◽  
Science Volume ◽  
Lessons Learned ◽  
Limited Resources ◽  
Annual Review ◽  
Publication Date ◽  
Socioeconomic Rights ◽  
Human Rights Movement

The human rights movement is increasingly using interdisciplinary, multidisciplinary, mixed-methods, and quantitative factfinding. There has been too little analysis of these shifts. This article examines some of the opportunities and challenges of these methods, focusing on the investigation of socioeconomic human rights. By potentially expanding the amount and types of evidence available, factfinding's accuracy and persuasiveness can be strengthened, bolstering rights claims. However, such methods can also present significant challenges and may pose risks in individual cases and to the human rights movement generally. Interdisciplinary methods can be costly in human, financial, and technical resources; are sometimes challenging to implement; may divert limited resources from other work; can reify inequalities; may produce “expertise” that disempowers rightsholders; and could raise investigation standards to an infeasible or counterproductive level. This article includes lessons learned and questions to guide researchers and human rights advocates considering mixed-methods human rights factfinding. Expected final online publication date for the Annual Review of Law and Social Science, Volume 17 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Conversation and Culture

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Simeon Floyd
Keyword(s):  
Conversation Analysis ◽  
Quantitative Methods ◽  
Sequential Analysis ◽  
Contemporary Literature ◽  
Annual Review ◽  
Publication Date ◽  
Face To Face ◽  
Qualitative And Quantitative Methods ◽  
Language Studies ◽  
Speech Communities

Conversation analysis is a method for the systematic study of interaction in terms of a sequential turn-taking system. Research in conversation analysis has traditionally focused on speakers of English, and it is still unclear to what extent the system observed in that research applies to conversation more generally around the world. However, as this method is now being applied to conversation in a broader range of languages, it is increasingly possible to address questions about the nature of interactional diversity across different speech communities. The approach of pragmatic typology first applies sequential analysis to conversation from different speech communities and then compares interactional patterns in ways analogous to how traditional linguistic typology compares morphosyntax. This article discusses contemporary literature in pragmatic typology, including single-language studies and multilanguage comparisons reflecting both qualitative and quantitative methods. This research finds that microanalysis of face-to-face interaction can identify both universal trends and culture-specific interactional tendencies. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mechanical Patterning in Animal Morphogenesis

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Yonit Maroudas-Sacks ◽  
Kinneret Keren
Keyword(s):  
Pattern Formation ◽  
Large Scale ◽  
Coarse Grained ◽  
Annual Review ◽  
Publication Date ◽  
Biochemical Processes ◽  
Substantial Progress ◽  
Biological Pattern Formation ◽  
Effective Theories ◽  
Biochemical Signals

Morphogenesis is one of the most remarkable examples of biological pattern formation. Despite substantial progress in the field, we still do not understand the organizational principles responsible for the robust convergence of the morphogenesis process across scales to form viable organisms under variable conditions. Achieving large-scale coordination requires feedback between mechanical and biochemical processes, spanning all levels of organization and relating the emerging patterns with the mechanisms driving their formation. In this review, we highlight the role of mechanics in the patterning process, emphasizing the active and synergistic manner in which mechanical processes participate in developmental patterning rather than merely following a program set by biochemical signals. We discuss the value of applying a coarse-grained approach toward understanding this complex interplay, which considers the large-scale dynamics and feedback as well as complementing the reductionist approach focused on molecular detail. A central challenge in this approach is identifying relevant coarse-grained variables and developing effective theories that can serve as a basis for an integrated framework for understanding this remarkable pattern-formation process. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Contemporary Management of Thyroid Nodules

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kristen Kobaly ◽  
Caroline S. Kim ◽  
Susan J. Mandel
Keyword(s):  
Thyroid Nodules ◽  
Cervical Lymphadenopathy ◽  
Standard Technique ◽  
Clinical History ◽  
Needle Aspiration ◽  
Annual Review ◽  
Publication Date ◽  
Molecular Testing ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kazunori Omote ◽  
Frederik H. Verbrugge ◽  
Barry A. Borlaug
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Treatment Strategies ◽  
Annual Review ◽  
Publication Date ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Prevalence Of Obesity

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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