Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease
PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell-types during development and in various manifestations of kidney pathology is the primary focus of this review.
KEY FINDINGS: PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell-types during development and in various manifestations of kidney pathology is the primary focus of this review.
BACKGROUND: Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule.
DETAILS: Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation - occurring immediately before the emergence of the fully mature nephron. These two cell-types therefore share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatio-temporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases such as Rapidly Progressive Glomerulonephritis (RPGN) and collapsing and cellular subtypes of Focal Segmental Glomerulosclerosis (FSGS) is closely allied with PEC proliferation and migration towards the capillary tuft - resulting in the formation of crescents and pseudo-crescents.
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Source: Bronstein, R., Pace, J., Gowthaman, Y., et al. (2023). Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease. Journal of the American Society of Nephrology . 2023; 10.1681/ASN.104. Published: February 16, 2023. DOI: 10.1681/ASN.0000000000000104.
Higher Ferritin Levels Associated With Increased Type 2 Diabetes Risk, Particularly in Women
A dose-response meta-analysis of 15 prospective studies involving 77,352 participants found that higher ferritin levels were associated with increased type 2 diabetes risk in both sexes. The association appeared stronger in women, with each 100-microgram-per-liter increase linked to a 53% higher risk compared with 21% in men. These findings highlight the potential value of investigating ferritin as a sex-specific marker of diabetes risk.
KEY FINDINGS: Higher circulating ferritin levels were associated with increased T2D risk in both men and women, with a stronger association observed in women in the primary sex-specific analysis after exclusion of a heterogeneous study. These findings suggest that ferritin may provide additional information for sex-specific diabetes risk assessment.
However, the meta-analysis establishes an association rather than causation. Differences in study populations, substantial between-study heterogeneity, and insufficient information on menopausal status limit interpretation. Further prospective research is needed to determine whether ferritin improves diabetes risk prediction beyond established clinical factors and whether the observed sex difference is consistent across diverse populations.
BACKGROUND: Iron metabolism has been implicated in glucose regulation and the development of type 2 diabetes (T2D). Ferritin, a marker of iron stores, has been associated with diabetes risk in observational studies, although findings have varied across populations. Because circulating ferritin concentrations differ between men and women, investigators conducted a dose-response meta-analysis to examine whether the association between ferritin levels and incident T2D varies by sex.
DETAILS: Researchers systematically searched PubMed, Web of Science, and EMBASE for prospective studies published through August 1, 2018. Fifteen studies involving 77,352 participants aged 20 to 80 years and 18,404 incident T2D cases were included. Follow-up ranged from approximately 3 to 17 years. The investigators assessed the relationship between circulating ferritin concentrations and T2D risk using pooled relative risk estimates and dose-response analyses. Sex-specific analyses were conducted to evaluate potential differences in the association between ferritin levels and diabetes development.
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Across all participants, each 100-microgram-per-liter increase in circulating ferritin was associated with a 22% higher risk of T2D (RR, 1.22; 95% CI, 1.14-1.31). In sex-specific analyses, after excluding a study contributing substantial heterogeneity, each 100-microgram-per-liter increase in ferritin was associated with a 53% higher T2D risk in women (RR, 1.53; 95% CI, 1.29-1.82), compared with a 21% increase in men (RR, 1.21; 95% CI, 1.15-1.27). The difference between sexes was statistically significant (P=0.020).
Nonlinear dose-response analyses also indicated that the association between ferritin and T2D risk was stronger in women than in men at comparable ferritin concentrations. The association remained evident after adjustment for several potential confounders, including inflammatory markers, body mass index, liver enzymes, and metabolic factors.
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Source: Jiang, L., Wang, K., Lo, K., et al. ex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. The Journal of Clinical Endocrinology & Metabolism. 2026; 104(10): 4539-4551. Published: August 22, 2026. DOI: 10.1210/jc.2019-00495.
Timing of Vascular Access Creation in Older Adults With ESKD
A prospective European cohort of older adults with ESKD found that only 32% of AVFs were created within the defined 6-month window before hemodialysis initiation, while 42% were created early and 26% late. The findings highlight the difficulty of predicting dialysis timing and the need for better tools to individualize vascular access planning.
KEY FINDINGS: In this European cohort of older adults with ESKD, vascular access creation frequently did not coincide with the timing of hemodialysis initiation. More than 4 in 10 AVFs were created early, while approximately 1 in 4 were created late, resulting in substantial use of CVCs at dialysis initiation. The findings highlight the difficulty of predicting dialysis initiation in older adults and support the development of clinical prediction tools to better individualize vascular access planning.
BACKGROUND: Planning vascular access for older adults with end-stage kidney disease (ESKD) is challenging because the timing of hemodialysis initiation is difficult to predict. Arteriovenous fistulas (AVFs) created too early may remain unused, whereas delayed creation can result in hemodialysis being initiated through a central venous catheter (CVC). This study evaluated the timing of vascular access creation relative to hemodialysis initiation in older patients across Europe.
DETAILS: This secondary analysis used data from the EQUAL cohort, a prospective observational study involving patients aged 65 years or older with stage 4 or 5 chronic kidney disease in six European countries. Patients were included when their estimated glomerular filtration rate fell below 15 mL/min/1.73 m², provided they received a vascular access and had at least 6 months of follow-up. AVF timing was categorized as early when hemodialysis did not begin within 6 months after AVF creation, on time when hemodialysis was initiated with an AVF within 6 months, and late when hemodialysis was initiated with a CVC before or within 6 months after AVF creation.
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A total of 332 patients were analyzed. An AVF was the first vascular access in 221 patients (67%), while 111 patients (33%) initially received a CVC. Among those initially receiving a CVC, 53 patients (48%) subsequently underwent AVF creation. At dialysis initiation, 158 patients (54%) were using an AVF and 136 (46%) were using a CVC. Among the 274 patients who underwent AVF creation, access was created on time in 88 patients (32%), early in 114 (42%), and late in 72 (26%). Despite the high proportion of early AVF creation, most fistulas were eventually used, with 90% of patients initiating hemodialysis within 3 years after AVF creation.
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Source: Heggen, B. D. C., Chesnaye, N. C., Dekker, F. W., et al. Vascular Access Surgery Timing: A Prospective European Cohort Study in Elderly Patients with ESKD. Kidney360. 2026; 7(9): 2066-2074. Published: September 22, 2026. DOI: 10.34067/KID.0000001180.
Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach
A structured approach to ECMO de-escalation and decannulation can reduce practice variability while incorporating patient and family preferences. Proactive symptom management may improve the patient and family experience, supporting a more comfortable and dignified end-of-life journey.
KEY FINDINGS: A structured, interprofessional approach to palliative ECMO de-escalation can reduce variability in end-of-life practice and support more consistent symptom management and communication. Incorporating patient and family preferences into the process, together with proactive symptom management and staff debriefing, was associated with a more comfortable and dignified end-of-life experience in this quality-improvement setting.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive, potentially lifesaving therapy associated with complications involving multiple organ systems. When ECMO is no longer considered beneficial, de-escalation or decannulation may be required as part of a transition to comfort-focused care and natural death. At a tertiary care facility with 64 beds using ECMO, variability was identified in ECMO initiation, communication with patients and families, determination of nonbeneficial therapy, and symptom management during de-escalation.
DETAILS: This quality-improvement project integrated palliative care, reviewed existing literature on best practices, and established an interprofessional task force focused on ECMO de-escalation. New clinical guidelines were developed to provide a consistent, evidence-based framework for communication, decision-making, symptom management, and de-escalation/decannulation. The initiative was designed to reduce practice variability while improving the experience of patients, families, and clinicians during transition to comfort-directed care.
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Implementation of the guidelines decreased practice variability and reduced patient and family stress and discomfort during ECMO de-escalation and decannulation. Team members reported decreases in symptoms of secondary trauma and moral distress associated with these situations. They also reported improved delivery of end-of-life care, including family education and support, patient advocacy, and symptom management. Family members valued greater attention to both patient and family well-being, while structured staff debriefings supported reflection and identification of opportunities for improvement.
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Source: Arbour, R., Abate, M., Garcia, O., et al. Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach. Critical Care Nurse. 2026; 46(4): 17-28. Published: August 1, 2026. DOI: 10.4037/ccn2026166.
Neovascular Glaucoma Associated With Increased Long-Term Mortality and Systemic Morbidity
A large TriNetX cohort study found that neovascular glaucoma was associated with increased long-term risks of mortality and systemic complications beyond underlying retinal vascular disease. At 10 years, NVG in patients with proliferative diabetic retinopathy was associated with higher mortality and end-stage renal disease, while NVG in patients with central retinal vein occlusion was associated with higher mortality and stroke risk. The findings highlight the potential value of coordinated ophthalmic and systemic care when NVG develops.
KEY FINDINGS: The development of NVG was associated with additional long-term systemic morbidity and mortality beyond the underlying PDR or CRVO in this large retrospective cohort. The strongest associations included mortality and ESRD among patients with PDR and mortality and stroke among those with CRVO. The findings suggest that development of NVG may identify patients with substantial systemic vascular risk and support closer coordination between ophthalmic and other medical specialties. Because the study was retrospective and based on electronic health records, the observed associations should not be interpreted as evidence that NVG itself directly causes these systemic outcomes.
BACKGROUND: Neovascular glaucoma (NVG) is a serious ocular complication of retinal vascular disease, including proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO). Although NVG is primarily recognized for its effects on vision and intraocular pressure, less is known about whether its development is associated with additional long-term systemic health risks. This multicenter retrospective cohort study evaluated mortality and major systemic outcomes among adults with PDR or CRVO who did or did not subsequently develop NVG.
DETAILS: The investigators used the TriNetX Research Network, a deidentified electronic health record database containing information from more than 177 million patients across more than 150 healthcare organizations worldwide. Adults older than 40 years with PDR or CRVO were identified and compared according to whether NVG subsequently developed. Patients were propensity-score matched 1:1 based on demographic characteristics and comorbidities. Outcomes were assessed at 1, 5, and 10 years and included all-cause mortality, stroke, myocardial infarction (MI), end-stage renal disease (ESRD), and deep-vein thrombosis (DVT). A total of 1,278 patients with PDR and NVG were matched with 1,278 patients with PDR without NVG. The study also evaluated patients with CRVO and NVG compared with matched CRVO patients without NVG, as well as an NVG cohort compared with a cataract control cohort.
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Among patients with PDR, development of NVG was associated with higher 10-year mortality (HR, 1.34; 95% CI, 1.14-1.57) and ESRD (HR, 1.43; 95% CI, 1.23-1.67) compared with PDR without NVG. Ten-year survival was 60.4% in the PDR + NVG group compared with 68.4% in the PDR without NVG group. Among patients with CRVO, those who developed NVG had higher 10-year mortality (HR, 1.61; 95% CI, 1.17-2.20) and stroke risk (HR, 1.86; 95% CI, 1.19-2.90). Differences in MI and ESRD were not statistically significant in this comparison, and DVT risk was also not significantly different. When PDR + NVG was compared directly with CRVO + NVG, the PDR + NVG group had higher 10-year risks of mortality (HR, 1.56; 95% CI, 1.17-2.07), MI (HR, 1.94; 95% CI, 1.13-3.32), and ESRD (HR, 4.04; 95% CI, 2.43-6.73). Compared with the cataract control cohort, NVG was associated at 10 years with higher risks of mortality (HR, 2.66; 95% CI, 2.40-2.94), stroke (HR, 2.17; 95% CI, 1.85-2.54), MI (HR, 1.89; 95% CI, 1.60-2.23), and ESRD (HR, 3.34; 95% CI, 2.89-3.88).
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Source: Margolis, R., Vasu, P., and Dorairaj, S. K. Long-Term Risk of Mortality and Systemic Morbidity in Neovascular Glaucoma: A Multicenter Retrospective Cohort Study. Ophthalmology Glaucoma. 2026; 9(5): 517-526. Published: September-October, 2026. DOI: 10.1016/j.ogla.2026.01.017.
Manual Detorsion by Pediatric Emergency Physicians May Shorten Ischemia Time in Pediatric Testicular Torsion
A study found that manual detorsion performed by pediatric emergency physicians can shorten ischemia time in children with testicular torsion. The findings highlight the potential value of prompt bedside intervention while definitive surgical management is being arranged. Manual detorsion remains a temporizing measure and does not replace urgent surgery.
KEY FINDINGS: The study highlights manual detorsion as a potentially useful time-saving intervention in pediatric testicular torsion. Having trained pediatric emergency physicians perform the procedure may allow restoration of testicular blood flow sooner and reduce the interval to definitive treatment. Because testicular viability is time-dependent, incorporating prompt manual detorsion into emergency management may be clinically relevant when appropriate expertise is available. The procedure should be viewed as an emergency temporizing measure followed by definitive surgical management.
BACKGROUND: Testicular torsion is a time-sensitive urologic emergency in which prolonged interruption of testicular blood flow can result in irreversible ischemic injury. Although definitive management requires urgent surgical detorsion and orchiopexy, manual detorsion may provide temporary restoration of blood flow while the patient is being prepared for surgery. This study evaluated whether manual detorsion performed by pediatric emergency physicians could reduce the time that the testis remains ischemic in children with testicular torsion.
DETAILS: The study examined pediatric patients with suspected testicular torsion who underwent manual detorsion by pediatric emergency physicians before definitive operative management. The investigators assessed the time from emergency department presentation to restoration of testicular perfusion and compared outcomes according to whether manual detorsion was successfully performed. The analysis focused on the potential role of emergency physicians in initiating immediate treatment rather than waiting for transfer to the operating room. Manual detorsion was considered an adjunct to, rather than a replacement for, definitive surgical management.
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Manual detorsion performed by pediatric emergency physicians was associated with a shorter duration of testicular ischemia before operative treatment. Successful bedside detorsion allowed restoration of perfusion to occur earlier than would have been possible if treatment had been deferred until surgical exploration. The findings support the potential value of emergency physicians performing manual detorsion promptly when pediatric testicular torsion is suspected, particularly when operating-room preparation or surgical consultation may introduce additional delays. Definitive surgical exploration remains necessary because manual detorsion does not reliably correct the underlying torsion or prevent recurrence.
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Source: Rivera, T., Lozano, J., Maniaci, V., et al. Manual Detorsion by Pediatric Emergency Physicians Shortens Ischemia Time in Pediatric Testicular Torsion. Academic Emergency Medicine. 2026; 33(9): e70412. Published: September, 2026. DOI: 10.1111/acem.70412.
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