[Posted 23/May/2023]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted.

BACKGROUND: Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD.

DETAILS: To test associations between protein carbamylation and the primary outcome of progression to ESKD, authors measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2-4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study. The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m², and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8-10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb <=5.80 mmol/mol), those in quartile 4 (C-Alb >10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR.

Copyright © American Society of Nephrology. All rights reserved.

Source: Kalim, S., Zhgao, S., Tang, M., et al. (2023). Protein Carbamylation and the Risk of ESKD in Patients with CKD.. Journal of the American Society of Nephrology. 2023; 34(5): 876-885. Published: May, 2023. DOI: 10.1681/ASN.0000000000000078.

[Posted 26/Jun/2026]

AUDIENCE: Endocrinology, Ob/Gyn, Internal Medicine

KEY FINDINGS: Insulin resistance in early pregnancy is strongly associated with total, regional, and ectopic adiposity. However, in late pregnancy, factors other than regional and ectopic adiposity predominately influence insulin sensitivity. Prepregnancy weight categories proportionately alter gestational weight gain, adiposity distribution, and glucometabolic responses.

BACKGROUND: Purpose of this study is to determine relationships between measurements of total body, visceral, and ectopic (liver, skeletal muscle) fat with insulin sensitivity in pregnancy.

DETAILS: Pregnant women of varying prepregnancy weights were prospectively studied in early (n = 59) and late (n = 47) gestation. At each visit, participants underwent body composition measurements including fat mass (FM), fat-free mass (FFM), abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), ectopic lipid amounts in liver (intrahepatic lipid [IHL]) and calf skeletal muscle (intramyocellular lipid [IMCL] and extramyocellular lipid), and hyperinsulinemia-euglycemic clamp to determine insulin sensitivity (Rd), endogenous glucose production (EGP), hepatic insulin sensitivity index (HISI), and free fatty acid (FFA) levels. In early pregnancy, Rd ([mg/kg FFM/min]/µIU/mL) inversely correlated (P values <0.05) with BMI, FM, SAT, VAT, IHL, IMCL, and FFA. HISI inversely correlated (P values <0.05) with BMI, FM, SAT, VAT, IMCL, and FFA but not with IHL. In late pregnancy, however, neither EGP ([mg/kg FFM/min]/µIU/mL) nor Rd correlated with regional or ectopic fat measures, but HISI remained inversely correlated with BMI, FM, SAT, VAT, and IMCL. Early-pregnancy IHL levels did not predict late-pregnancy insulin sensitivity. Pregnant women with prepregnancy obesity were more insulin resistant but gained less gestational weight, VAT, and SAT, and experienced less decline in insulin sensitivity, than normal prepregnancy weight women.

Copyright © American Diabetes Association. All rights reserved.

Source: Purnell, J. Q., Marshall, N., Francisco, M., et al. Relationships Between Regional and Ectopic Adiposity and Insulin Sensitivity in Early and Late Pregnancy. Diabetes Care. 2026; 49(7)): 1175-1184. Published: July 22, 2026. DOI: 10.2337/dc25-2081

[Posted 25/Jun/2026]

AUDIENCE: Nephrology, Endocrinology

KEY FINDINGS:

• The study identified skeletal muscle as a novel source of fibroblast growth factor 23 (FGF23) in scenarios of hyperphosphatemia, including high dietary phosphate intake and CKD.
• Skeletal muscle–derived FGF23 had endocrine actions lowering serum phosphate levels, which may protect from hyperphosphatemia-induced tissue damages.
• Skeletal muscle–derived FGF23 might also have paracrine effects counteracting atrophy.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a hormone that reduces the renal reabsorption of phosphate in response to systemic phosphate elevations. In CKD, serum levels of phosphate and FGF23 reach levels that can harm various tissues. While the bone acts as the main production site for FGF23, bone-specific gene deletion studies in mice suggest the existence of other FGF23 sources. Here, authors determine if skeletal muscle produces FGF23 in response to phosphate elevations. Authors studied four mouse models with phosphate elevations, two with CKD (global Col4a3 deletion and adenine-rich diet) and two without CKD (genetic klotho deficiency and high-phosphate diet). Furthermore, generated a new mouse line with skeletal muscle–specific Fgf23 deletion (KO), which received an adenine-rich or a high-phosphate diet. Mmeasured skeletal muscle FGF23 by quantitative real-time PCR, ELISA, and immunohistochemistry, as well as serum levels of phosphate, FGF23, and parathyroid hormone (PTH). Determined FGF23 mRNA levels in muscle biopsies from patients with CKD, and studied the effects of phosphate and PTH elevations on FGF23 expression in cultured myotubes isolated from mice and patients with CKD. Finally, studied the effects of acute phosphate loading on urine phosphate levels in Fgf23 KO mice. All four mouse models with phosphate and PTH elevations showed FGF23 expression in skeletal muscle tissue on mRNA and protein level. Phosphate, but not PTH, induced FGF23 expression in cultured myotubes. Furthermore, patients with CKD with higher serum phosphate levels expressed more FGF23 in skeletal muscle. Fgf23 KO mice had elevated serum phosphate levels when administered a high-phosphate diet and decreased urine phosphate levels after acute phosphate loading.

DETAILS:

Copyright © American Society of Nephrology. All rights reserved.

Source: Heitman, K., Li, Q., Fajol, A., et al. Systemic Phosphate Elevations Induce Fibroblast Growth Factor 23 Production in Skeletal Muscle to Reduce Renal Phosphate Reabsorption in Mice. Journal of the American Society of Nephrology. 2026; 37(6): 1160-1173. Published: June, 2026. DOI: 10.1681/ASN.0000000963

[Posted 24/Jun/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS:

• FDA approved the first generic form of baloxavir marboxil tablets.
• Approved for patients aged 5 years and older.
• Indications include acute uncomplicated influenza treatment and post-exposure prophylaxis.
• Treatment eligibility requires symptom duration of no more than 48 hours.
• Contraindicated in patients with hypersensitivity to baloxavir marboxil or formulation ingredients.
• Common adverse effects: diarrhea, bronchitis, nausea, sinusitis, and headache.
• In the U.S., nine out of 10 prescriptions filled are for generic drugs.
• Approval granted to Norwich Pharmaceuticals, Inc.

BACKGROUND: The U.S. Food and Drug Administration (FDA) announced approval of the first generic version of baloxavir marboxil tablets, previously marketed as Xofluza. This approval introduces the first single-dose generic option for both treatment and post-exposure prophylaxis of influenza. The approval was issued ahead of the 2026–2027 influenza season with the objective of expanding access to generic medications and supporting public health preparedness.

DETAILS: Generic baloxavir marboxil tablets are approved for use in patients aged 5 years and older. Indications include treatment of acute uncomplicated influenza in individuals who have experienced symptoms for no more than 48 hours and who are either otherwise healthy or at elevated risk for influenza-related complications. The medication is also approved for post-exposure prophylaxis following contact with an infected individual.

The drug is contraindicated in patients with known hypersensitivity to baloxavir marboxil or any formulation components. Safety considerations include warnings regarding increased incidence of treatment-emergent resistance in patients younger than 5 years of age.

Common adverse effects reported include diarrhea, bronchitis, nausea, sinusitis, and headache.

FDA approval of generic baloxavir marboxil provides an additional therapeutic option for influenza management through a single-dose regimen. Increased availability of generic alternatives may support broader patient access and affordability while maintaining treatment availability before the upcoming flu season.

Copyright © Skyscape Editorial Team. All rights reserved.

Source: News Release: FDA Approves First Single-Dose Generic Treatment for Influenza.. FDA. Published: June 17, 2026.

[Posted 15/Jun/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

BACKGROUND: Influenza outbreaks in nursing homes (NHs) pose a substantial threat to older adults, often resulting in morbidity and mortality. The Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend prompt postexposure prophylaxis, also termed chemoprophylaxis or prophylaxis with oseltamivir, for all residents who are not ill to limit influenza spread in NHs. Purpose of the study is to examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

DETAILS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.

Exposures: Intensive antiviral chemoprophylaxis with oseltamivir (>=70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Among 404 outbreaks in 318 NHs, 35,086 resident-trial observations (29,683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17,155 observations; 17,931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.

Copyright © American Medical Association. All Rights Reserved.

Source: Silva, J. B. B., Hsieh, H. T., Howe, C. J., et al. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Internal Medicine.. 2026; 186(6): 714-722. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0401

An Emulated Target Trial.

[Posted 8/Jun/2026]

AUDIENCE: Dermatology, Ob/Gyn

KEY FINDINGS: Treatment with SGLT2i was associated with favorable clinical outcomes in patients with psoriasis and comorbid T2DM. These findings support investigation of SGLT2i as an adjunct therapy in this population.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, including:

• Type 2 diabetes mellitus (T2DM)
• Cardiovascular disease
• Chronic kidney disease (CKD)
• Psychiatric disorders
• Psoriasis and T2DM share common inflammatory pathways and may increase the risk of developing one another.
• While DPP4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP1RA) have shown benefits in psoriasis, the impact of SGLT2 inhibitors on psoriasis-related outcomes remained unclear.

Purpose of this study is to evaluate the safety and effectiveness of SGLT2 inhibitors in patients with psoriasis and concomitant T2DM, compared with:

• DPP4 inhibitors (DPP4i)
• GLP-1 receptor agonists (GLP1RA)

DETAILS: This emulated target trial included adults with psoriasis and T2DM initiating SGLT2i, DPP4i, or GLP1RA between 2013 and 2025. SGLT2i initiators were propensity score-matched to DPP4i initiators and GLP1RA initiators, respectively. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the outcomes. A total of 8799 SGLT2i initiators and 8799 matched DPP4i initiators with psoriasis and comorbid T2DM, and 11,550 SGLT2i initiators and 11,550 matched GLP1RA initiators, were included. Compared with DPP4i, treatment with SGLT2i was associated with significantly lower all-cause mortality (HR = 0.633, 95% CI = 0.564-0.711) and reduced risks of emergency visits (HR = 0.915, 95% CI = 0.871-0.961), acute kidney injury (HR = 0.834, 95% CI = 0.759-0.916), chronic kidney disease (HR = 0.866, CI = 0.791-0.949), end-stage renal disease (HR = 0.555, 95% CI = 0.438-0.703), and severe sepsis (HR = 0.689, CI = 0.594-0.799). Compared with GLP1RA, treatment with SGLT2i was associated with reduced risks of asthma (HR = 0.822, 95% CI = 0.713-0.946), depression (HR = 0.887, CI = 0.801-0.983), sleep disorders (HR = 0.856, CI = 0.783-0.936), and malignancies (HR = 0.852, 95% CI = 0.764-0.951).

Copyright © Elsevier Ltd. All rights reserved.

Source: Cheng, D., Ji, H., Theodosakis, N., et al. Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Psoriasis and Comorbid Type 2 Diabetes: A Population-Based Target Trial Emulation Journal of the American Academy of Dermatology. 2026; 94(6): 1686-1696. Published: June, 2026. DOI: 10.1016/j.jaad.2026.02.008