Apolipoprotein A-IV Concentrations and Clinical Outcomes In A Large CKD Cohort
ApoA-IV appears to be an independent risk marker for reduced all-cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.
KEY FINDINGS: The data support a link between elevated apoA-IV concentrations and reduced inflammation in moderate CKD. ApoA-IV appears to be an independent risk marker for reduced all-cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.
BACKGROUND: Chronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A-IV (apoA-IV) has antiatherogenic, antioxidative, anti-inflammatory and antithrombotic properties and levels increase significantly during the course of CKD. Study aimed to investigate the association between apoA-IV and all-cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study.
DETAILS: This was a prospective cohort study including 5141 Caucasian patients with available apoA-IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30-60 ml/min/1.73m2 or an eGFR >60 ml/min/1.73m2 in the presence of overt proteinuria. Median follow-up was 6.5 years. The association of apoA-IV with comorbidities at baseline and endpoints during follow-up was modelled adjusting for major confounders. Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA-IV quartile had the lowest high-sensitivity C-reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA-IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72-0.86, p = 0.0000003). During follow-up, each 10 mg/dl higher apoA-IV was significantly associated with a lower risk for all-cause mortality (600 cases, hazard ratio [HR] = 0.81, 95% CI 0.73-0.89, p = 0.00004), incident major adverse cardiovascular events (506 cases, HR = 0.88, 95% CI 0.79-0.99, p = 0.03) and death or hospitalizations due to heart failure (346 cases, HR = 0.84, 95% CI 0.73-0.96, p = 0.01).
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Source: Schwaiger, J. P., Kollerits, B., Steinbrenner, I., et al. (2022). Apolipoprotein A-IV Concentrations And Clinical Outcomes In A Large Chronic Kidney Disease Cohort: Results from the GCKD Study. Journal of Internal Medicine. 2022; 291(5): 622-636. Published: May, 2022. DOI: 10.1111/joim.13437.
Kidney Juxtaglomerular Cells' Renin Shutdown Mechanism in Blood Pressure Regulation
Juxtaglomerular cells monitor calcium levels to toggle renin release. Studying live tissue outperforms isolated cell models for understanding renin regulation. Targeting renin suppression could yield novel hypertension therapies and reduce related complications.
KEY FINDINGS: The findings demonstrate that juxtaglomerular cells shut down renin production through calcium-mediated mechanisms observed directly in kidney tissue. This approach highlights the brakes on hormone systems, differing from traditional focus on activation pathways.
BACKGROUND: Juxtaglomerular cells in the kidney serve as key sensors for blood pressure homeostasis. These cells release renin, a hormone that elevates blood pressure when levels drop too low. They rely on intracellular calcium as an on-off switch to control renin production, preventing hypotension.
DETAILS: Juxtaglomerular cells function as the body's primary baroreceptors, constantly assessing systemic blood pressure through mechanosensory mechanisms in the afferent arterioles. When pressure falls, these cells detect reduced stretch and rising intracellular calcium, triggering renin release to activate the renin-angiotensin-aldosterone system (RAAS). This study shifts focus to the inhibitory phase: how elevated calcium levels or other signals in intact kidney tissue suppress renin synthesis, acting as a regulatory "brake" to prevent overactivation. Traditional research emphasized renin induction using isolated cell cultures, which overlooked tissue-specific interactions like interstitial signaling and vascular coupling. By contrast, this work analyzed living kidney slices, revealing precise calcium-dependent shutdown pathways that halt transcription and secretion in real-time. This tissue-level insight explains why excessive renin persists in hypertension, potentially due to faulty off-switches, and opens avenues for therapies targeting suppression rather than blockade alone—such as modulating calcium channels or downstream inhibitors.
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Medical Policy Brief: Shift in Universal Hepatitis B Vaccine Recommendation
The ACIP voted 8-3 to end the universal HepB birth dose recommendation. Vaccination at birth is recommended only for infants of mothers who are positive for HepB or have unknown status. Mothers who test negative are advised to consult their healthcare provider to decide the timing of their child's vaccination. A change in the recommendation, if approved by the CDC Director, could affect state policies and private insurance coverage of the vaccine.
KEY FINDINGS:
- Vote Margin: The ACIP voted 8-3 to end the universal HepB birth dose recommendation.
- New Guidance: Vaccination at birth is recommended only for infants of mothers who are positive for HepB or have unknown status.
- Negative Mothers: Mothers who test negative are advised to consult their healthcare provider to decide the timing of their child's vaccination.
- Policy Impact: A change in the recommendation, if approved by the CDC Director, could affect state policies and private insurance coverage of the vaccine.
BACKGROUND: The Hepatitis B (HepB) vaccine has historically been universally recommended for all infants at birth by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP). This policy ensures protection against perinatal transmission and helps reduce the overall disease burden.
DETAILS: The CDC's Advisory Committee on Immunization Practices (ACIP) recently held a vote to reconsider the universal recommendation for the HepB vaccine at birth. The panel voted by a margin of 8-3 to cease the blanket recommendation that all infants receive the vaccine at birth. The new guidance maintains the recommendation only for infants whose mothers test positive for the infection or have unknown status. Mothers who test negative for Hepatitis B would be advised to "talk with their healthcare provider and decide themselves when to vaccinate their child." The discussion involved controversy, including a newly appointed ACIP member without medical training who reportedly argued against the universal birth dose, claiming vaccines had "never tested (the vaccines) appropriately." Dr. Cody Meissner, the sole continuing ACIP member, criticized the proposed change, stating "no rational science [had] been presented" to justify it. The ACIP voted in favor of changing the recommendations. These recommendations must now go to the CDC director for approval. While states ultimately set their own immunization policies, they generally rely on CDC guidelines. A change in ACIP recommendations can also influence insurance coverage, as most private insurers are required to cover recommended vaccines.
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Acute Angle Closure Incidence in a Large Countywide Safety Net Teleretinal Screening Program
AAC risk was less than 1 in 40,000 per dilation in a high-volume TDRS program serving a diverse safety net population, supporting the overall safety of dilation in this setting. Further discussion about AAC risk as a contraindication to dilation is warranted.
KEY FINDINGS: AAC risk was less than 1 in 40,000 per dilation in a high-volume TDRS program serving a diverse safety net population, supporting the overall safety of dilation in this setting. Further discussion about AAC risk as a contraindication to dilation is warranted.
BACKGROUND: Pharmacologic pupillary dilation is vital for eye disease screening but is often avoided due to concerns about triggering acute angle closure (AAC), a sight-threatening ophthalmic emergency. Aim of this study was to assess AAC incidence after dilation and validate the use of International Classification of Diseases (ICD) codes for identifying AAC cases.
DETAILS: his retrospective cohort study used data from a primary care–based teleretinal diabetic retinopathy screening (TDRS) program. Eligible participants were Los Angeles County Department of Health Services patients who underwent teleretinal screening by dilated fundus photography between August 23, 2013, and March 1, 2024. Potential AAC cases were identified using ICD codes for angle closure, including AAC glaucoma, primary angle-closure glaucoma, and anatomical narrow angle, within 3 months of dilation. All urgent care, emergency department, and eye clinic encounters within the next calendar day after TDRS and encounters with Current Procedural Terminology codes for iridectomy/iridotomy or lens extraction within 14 calendar days of TDRS were also identified. Manual medical record review was conducted to verify AAC cases and extract clinical information. Data were analyzed from July 2024 to June 2025. Of 84,008 included patients, 46,255 (55.1%) were female, and the mean (SD) age was 55.4 (10.7) years. There were a total of 168,796 dilations, with a mean (SD) of 2.01 (1.50) dilations per patient. Manual medical record review confirmed 4 AAC cases after dilation: 3 coded as AAC glaucoma and 1 as anatomical narrow angle. The AAC risk was 2.4 (95% CI, 0.05-4.69) per 100,000 dilations (0.002%) or 4.8 (95% CI, 0.10-9.43) per 100,000 patients (0.005%). All 4 AACs occurred in female patients, had narrow angles in the nonpresenting eye on gonioscopy, and presented within 1 day with AAC symptoms, including eye pain and blurry vision.
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Source: Lang, T. Z., Xu, B. Y., Li, Z., et al. Acute Angle Closure Incidence in a Large Countywide Safety Net Teleretinal Screening Program. JAMA Ophthalmology. 2025; 143(11): 883-890. Published: December, 2025. DOI: 10.1001/jamaophthalmol.2025.3162.
Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis
The findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron-mediated hepcidin regulation in the absence of BMP2 and BMP6.
KEY FINDINGS: Together with other published data, these findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron-mediated hepcidin regulation in the absence of BMP2 and BMP6.
BACKGROUND: The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. Authors have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo.
DETAILS: Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis. Although both HJV and HFE regulate hepcidin, at least partly, by functionally interacting with the BMP–SMAD pathway, the mechanisms are incompletely understood. Notably, both HJV and HFE can regulate hepcidin in a BMP6-independent manner. To understand whether HJV and HFE influence hepcidin regulation by BMP2 and/or BMP5, authors investigated the iron phenotype of mice with combined mutations in endothelial Bmp2/Hjv and Bmp5/Hfe. Authors found that endothelial Bmp2/Hjv double knockout (KO) mice exhibit more severe hepcidin deficiency and iron overload than single endothelial Bmp2 or Hjv KO mice, similar to previous findings in mice with double endothelial Bmp2/Hfe KO and Bmp6/Hjv KO, or a functional loss of both Bmp6 and Hfe. Moreover, authors found that iron completely fails to induce hepcidin in both endothelial Bmp2/Hjv and Bmp2/Hfe double KO mice. In contrast, a functional loss of BMP5 does not worsen hemochromatosis in Hfe KO mice.
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Source: Xiao, X., Moschetta, G. A., Chowdhury, S. B., et al. Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis. American Journal of Hematology. 2025; 100(12): 2175-2184. Published: December, 2025. DOI: 10.1002/ajh.70055.
Telomere Dysfunction in Renal Tubular Epithelial Cells Leads to Kidney Fibrosis
Trf1 deletion in renal tubular epithelial cells led to renal tubulointerstitial fibrosis, contributing to CKD pathogenesis and progression. Loss of Trf1 induced cellular senescence, DNA damage, and telomere shortening and activated regenerative repair. Trf1 deletion triggered kirsten rat sarcoma viral oncogene homolog and TNF-alpha signaling through NF-KB pathway in renal tubules, suggesting a key molecular mechanism in CKD progression.
KEY FINDINGS: The study underlies a role of renal tubular epithelial cells in the development and progression of kidney fibrosis and CKD induced by telomere dysfunction.
BACKGROUND: Renal tubular epithelial cells are the critical mediators of kidney fibrogenesis. Telomere dysfunction has been associated with kidney injury and fibrosis. However, the role of telomere dysfunction specifically in renal tubular epithelial cells in the onset and progression of kidney fibrosis remains poorly understood. TRF1 is a critical component of the telomeric protective complex known as shelterin, and its deficiency results in telomere dysfunction.
DETAILS: To investigate the impact of telomere dysfunction on kidney injury and fibrosis, authors generated mice depleted for the shelterin component TRF1 specifically in renal tubular epithelial cells.vGenetic ablation of Trf1 caused decline in kidney function accompanied by increased tubular injury and tubulointerstitial fibrosis 8 weeks after TRF1 depletion, concomitant with excessive accumulation of extracellular matrix, cell cycle arrest at G2/M phase, and telomeric damage. Trf1Δ/Δ mice activated regenerative repair mechanisms, supporting proliferation-mediated telomere shortening in renal tubular epithelial cells. At humane end point, Trf1Δ/Δ mice displayed elevated urinary albumin-to-creatinine ratio (UACR), associated with augmented interstitial fibrosis and tubular atrophy eventually leading to CKD. At the mechanistic level, authors reported the unprecedented finding that Trf1 deletion upregulates the Ras–Raf–Mek–Erk, PI3k/Akt/mammalian target of rapamycin, and p38 pathways.
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Source: Saraswati, S., Martínez, P., Serrano, R., et al. Telomere Dysfunction in Renal Tubular Epithelial Cells Leads to Kidney Fibrosis. Journal of the American Society of Nephrology. 2025; 36(12): 2348-2363. Published: December, 2025. DOI: 10.1681/ASN.0000000771.
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