Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP).

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.

Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease.

Glycerol-3-phosphate contributes to the increase in FGF23 production in chronic kidney disease.

Why fibroblast growth factor 23 (FGF23) levels increase markedly in chronic kidney disease (CKD) is unknown. Recently, we found that phosphate stimulates renal production of glycerol-3-phosphate (G-3-P), which circulates to the bone to trigger FGF23 production. To assess the impact of G-3-P on FGF23 production in CKD, we compared the effect of adenine-induced CKD in mice deficient in glycerol-3-phosphate dehydrogenase 1 (Gpd1), an enzyme that synthesizes G-3-P, along with wild-type littermates.

Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease.

Rationale & Objective: Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease globally. We aim to identify proteomic and metabolomic correlates of histologically confirmed DKD that may improve our understanding of its pathophysiology.

Study Design: A cross-sectional study.

A Metabolomics Approach to Identify Metabolites Associated With Mortality in Patients Receiving Maintenance Hemodialysis.

Introduction: Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis.

Methods: We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants.

Sodium-glucose cotransporter 2 inhibitors ameliorate ER stress-induced pro-inflammatory cytokine expression by inhibiting CD36 in NAFLD progression in vitro.

Sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors, antidiabetic drugs that reduce blood sugar levels by inhibiting glucose reabsorption in the renal proximal tubules, also ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of SGLT2 inhibition on hepatic steatosis and nonalcoholic steatohepatitis (NASH) using an in vitro model of NAFLD progression. HepG2 cells and a coculture of Hepa1c1c7 and Raw 264.

Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study.

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.

Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development.

Evaluation and Significance of Nonvisualization of the Cavum Septum Pellucidum on Prenatal Ultrasonography.

Importance: The identification of the cavum septum pellucidum (CSP) is an integral part of the routine second trimester fetal anatomy scan. The absence or nonvisualization of the CSP has significant clinical implications and requires further evaluation and counseling for the pregnant patient.

Objective: The aim of this review is to review the importance of accurate sonographic identification of the CSP and the underlying pathologies that can be associated with nonvisualization of this structure.

Longitudinal Analysis of Diabetes Mellitus Risk: Smoking Status and Smoking Cessation.

: Smoking cessation is acknowledged for its health benefits. However, it paradoxically increases diabetes mellitus (DM) risk shortly after quitting due to weight gain. This research aimed to investigate how smoking status could affect the development of DM, focusing on how the risk of acquiring diabetes changed over time after quitting smoking, independent of variables such as weight gain.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults.

Background: There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation.

Methods: We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK).

Serum and Urine Metabolites and Kidney Function.

Key Points: We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort. Metabolic profiling in serum and urine provides distinct and complementary insights into disease.

Background: Metabolites represent a read-out of cellular processes underlying states of health and disease.

siRNA takes a jab at hypertension.

Hypertension is a modifiable risk factor for cardiovascular disease, the leading cause of death worldwide, yet most US adults with hypertension do not meet goal blood pressure. KARDIA-1 demonstrates the efficacy of zilebesiran, a subcutaneously administered small interfering RNA, for lowering blood pressure, presenting a novel treatment option for this deadly disease..

Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD.

Key Points: Longitudinal untargeted metabolomics. Children with CKD have a circulating metabolome that changes over time.

Background: Understanding plasma metabolome patterns in relation to changing kidney function in pediatric CKD is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions.

Plasma Proteins Associated with Chronic Histopathologic Lesions on Kidney Biopsy.

Key Points: Proteomic profiling identified 35 blood proteins associated with chronic histopathologic lesions in the kidney. Testican-2 was expressed in the glomerulus, released by the kidney into circulation, and inversely associated with glomerulosclerosis severity. NELL1 was expressed in tubular epithelial cells, released by the kidney into circulation, and inversely associated with interstitial fibrosis and tubular atrophy severity.

Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression.

Key Points: Integrated analysis of proteome and metabolome identifies modules associated with CKD progression and kidney failure. Ephrin transmembrane proteins and podocyte-expressed CRIM1 and NPNT emerged as central components and warrant experimental and clinical investigation.

Background: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes.

Plasma metabolites and physical function in patients undergoing hemodialysis.

Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.

Phosphate sensing in health and disease.

Purpose Of Review: Disruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12-18 months.

Gα11 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia.

Fibroblast growth factor 23 (FGF23) production has recently been shown to increase downstream of Gαq/11-PKC signaling in osteocytes. Inactivating mutations in the gene encoding Gα11 (GNA11) cause familial hypocalciuric hypercalcemia (FHH) due to impaired calcium-sensing receptor signaling. We explored the effect of Gα11 deficiency on FGF23 production in mice with heterozygous (Gna11+/-) or homozygous (Gna11-/-) ablation of Gna11.

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study.

Rationale & Objective: Hemoglobin A (HbA) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown.